compositions

Abstract

Compositions which may be useful as inhibitors and / or capturers of reactive oxygen species ("ROS"), and which may be particularly useful in topical consumer skincare products.

Description

Compositions Technical field

[0001] The present invention generally relates, inter alia, to compositions which may be useful as inhibitors and / or capturers of reactive oxygen species (“ROS”), and which may be particularly useful in topical consumer skincare products. Background of the Invention

[0002] Skin is the most visible and the widest exposed organ and reflects the general health condition and the aging process in humans. Skin, the largest organ in the human body, is exposed to air pollutants, including diesel exhaust fumes, ultraviolet rays, food, xenobiotics, drugs, and cosmetics, which promote the production of reactive oxygen species (ROS). Reactive oxygen species are highly reactive chemicals and can give rise to other radical species such as reactive nitrogen species (RNS), reactive sulfur species, and reactive carbon species. Specific examples of ROS that can be harmful to skin include superoxide, hydroxy radical, singlet oxygen, peroxide, nitric oxide, and peroxynitrite.

[0003] ROS are involved in complex and diverse reaction pathways, including the activation and upregulation of matrix metalloproteinases (MMPs) that degrade collagen, a hallmark of skin aging leading to formation of wrinkles. Oxidative stress may involve an increase in the production of ROS and other oxidants that exceeds the skin’s intrinsic antioxidant capacity. Current knowledge on ROS-related and oxidative stress-related skin diseases is that ROS is a factor in skin aging and inflammation.

[0004] To counter the effects of ROS, the skin has developed multiple antioxidant defense systems, including enzymatic, e.g., the glutathione-peroxidase-reductase enzyme system and superoxide dismutase (SOD) and non-enzymatic, e.g., vitamin C, vitamin E, glutathione, and coenzyme Q10. These antioxidants play an important role in the mitigation of oxidative stress in the skin, thereby reducing the signs of skin aging, and in the treatment of some UV-sensitive dermatosis, such as polymorphic light eruption, prurigo aestivalis, solar urticaria, and porphyria.

[0005] According to their mechanisms of action, antioxidants can be classified as ROS capturers or ROS inhibitors. ROS capturers, such as polyphenolic compounds with several hydroxyl groups (-OH), are involved in the scavenging of ROS, and havethe capacity to convert ROS directly into stable products, by donating hydrogen or electrons, and thereby reducing the concentration and downstream effects of ROS. In contrast, ROS inhibitors function by reducing the quantity of ROS generated under stress conditions. Multifunctional antioxidants can display the properties of both ROS capturers and ROS inhibitors.

[0006] ROS capturing antioxidants may “hunt” or scavenge the ROS before damage occurs and therefore may lessen the downstream aging pathways but their effect is limited and variable. As the mechanism of ROS capturing antioxidants is to directly react with ROS, the antioxidant must come into contact with the ROS before the ROS causes damage elsewhere. Given the high reactivity of ROS, the effectiveness of ROS capturing antioxidants is limited. However, ROS inhibiting antioxidants are able to reduce the formation of ROS, effectively stopping it before it can cause damage.

[0007] One of the primary sources of ROS in photoaging is UV light. Both UVA and UVB radiation are a source of ROS to some extent. However, with its longer wavelength and greater abundance in the solar spectrum, UVA poses a greater risk of ROS formation, particularly in deep skin layers such as the dermis. Radicals generated by photo exposure may directly damage the DNA and lipids of epidermal keratinocytes and skin fibroblasts. ROS and free radicals may activate transcriptional factors and modify gene expression. As a result, collagen fibers can be degraded by enzymes such as MMP (e.g. MMP-1). Protease-activated receptor 2 has been reported to induce ROS- related inflammation via the Akt-NF-κB pathway with the suppression of FoxO6 during skin photoaging.

[0008] UVA radiation passes through clouds and through glass. Its ability to generate ROS and the subsequent deleterious effects are compounded daily, even under circumstances when use of a UVB protective sunscreen is not warranted. In any case, sunscreens are generally not focused on preventing skin photo-aging (which may primarily be caused by UVA). Active ingredients in sunscreens also have many potential drawbacks including potential safety concerns, formulation challenges, adverse skin feel / appearance, and costs.

[0009] Recognizing the potential for anti-aging effects, antioxidants are often found in anti-aging serums, moisturizers, cleansers, lotions, oils and may also beincorporated into some sunscreens. However, these products typically employ ROS capturing antioxidants with limited effectiveness and frequently do not include ROS inhibiting antioxidants designed to also inhibit the generation of ROS by removing a primary source. Some sunscreens do contain both ROS capturing antioxidants intended to scavenge ROS and ROS inhibiting antioxidants that inhibit ROS formation by UVA absorption, though this is never the primary purpose of the sunscreen and the protection from ROS is limited. Sunscreens are designed to prevent sunburn by absorbing UVB rays and therefore they contain active ingredients designed to absorb UVB light. These active ingredients have many potential drawbacks including potential safety concerns, formulation challenges, adverse skin feel / appearance, and costs.

[0010] In particular, organic sunscreen active ingredients can result in a sticky and tacky feel after topical application, and inorganic sunscreen active ingredients are difficult to apply and typically leave a white-cast upon application. Furthermore, the addition of sunscreen active ingredients to an antiaging formulation can result in formulation challenges related to the solubility, stability, and compatibility of the active ingredients.

[0011] Perhaps most importantly, the daily application of sunscreen active ingredients carries certain safety risks which should be avoided when protection from direct sunlight is not required (e.g. indoors). Human health concerns around organic (i.e., chemical) sunscreen filters stem from in vitro and animal data indicating endocrine disruption effects and developmental toxicity, as well as from data showing that these compounds are systemically absorbed after normal topical use. These concerns chiefly arise from two clinical trials conducted by FDA scientists, both of which measured blood levels of organic sunscreen filters in various formulations (including lotion, cream, aerosol spray, nonaerosol spray and pump spray) after topical application. The pilot study in 24 healthy volunteers found that plasma concentrations of the four organic filters tested (avobenzone, oxybenzone, octocrylene and ecamsule) all exceeded the threshold for waiving some nonclinical toxicology studies for sunscreens (0.5 ng / mL), with mean maximum concentrations (Cmax) ranging from 1.5 ng / mL to 209.6 ng / mL after four applications on Day 1 under maximum use conditions (2 mg / cm2 of skin over 75% of body surface area [BSA]) (Matta, Murali K et al. “Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen ActiveIngredients: A Randomized Clinical Trial.” JAMA vol.321,21 (2019): 2082-2091). In the second study, in 48 healthy volunteers, all six of the organic filters tested (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, octinoxate) resulted in mean Cmax values greater than 0.5 ng / mL after a single application under maximum use conditions and mean Cmax values up to 7.1, 258.1, 7.8, 23.1, 5.8 and 7.9 ng / mL for avobenzone, oxybenzone, octocrylene, homosalate, octisalate and octinoxate, respectively, after 4 days of maximum use application (Matta, Murali K et al. “Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial.” JAMA vol.323,3 (2020): 256-267). These plasma levels are 10- to 500- fold higher than the threshold required for determination as Generally Recognized as Safe and Effective (“GRASE”) determination without additional toxicology data.

[0012] There is a need for antiaging products that can more effectively inhibit ROS generation by removing its primary source without exclusion of UVB light and the exposure to UVB-absorbing active ingredients which pose their own safety and formulation concerns. Summary of the Invention

[0013] In one aspect, the invention relates to compositions comprising an antioxidant system, wherein the antioxidant system comprises ROS agents. Advantageously, the ROS agents may be selected to provide both high ROS capture and ROS inhibition. In a particular embodiment, the antioxidant system comprises an ROS capturer and / or an ROS inhibitor. In a more particular embodiment, the ROS agents comprise a polymeric ROS agent and a free ROS agent. This combination of a polymeric ROS agent and a free ROS agent may advantageously provide a composition having particularly high ROS capture and ROS inhibition properties.

[0014] In a particular aspect, the invention provides a topical composition suitable for use as an anti-aging skincare product having: (i) an in vivo SPF of no more than 15; and (ii) a %UVA-T of no more than 10%, and / or a UVA-PF of at least 25, as measured by hybrid diffuse reflectance spectroscopy; and comprising an antioxidant system comprising an ROS capturer and / or an ROS inhibitor.

[0015] The compositions of the invention may help to reduce damage to the skin caused by ROS, e.g., by both capturing ROS and inhibiting ROS formation by absorbing high proportions of incident UVA radiation. Accordingly, in some embodiments the compositions of the invention will have a %UVA-T of no more than 10%. Alternatively, or in addition, in some embodiments the compositions of the invention will have a UVA- PF of at least 25 (e.g., as measured by hybrid diffuse reflectance spectroscopy; optionally, as measured by a method of hybrid diffuse reflectance spectroscopy described herein).

[0016] The compositions of the invention may provide protection for the skin from damage caused by UV-generated ROS but it is not required that the compositions are sunscreens. In particular embodiments, the compositions of the invention are not sunscreens (e.g., the compositions of the invention may contain substantially no organic UV filters, and optionally substantially no mineral UV filters). Usefully, this allows certain organic UV filters, which may be systemically absorbed through the skin of the user, to be omitted from compositions of the invention whilst retaining beneficial protection against skin photo-aging. Accordingly, in certain embodiments, compositions of the invention may have an SPF of less than 20. In particular embodiments, compositions of the invention may have an SPF no more than 15. More particularly, compositions of the invention may have an SPF of less than 15.

[0017] The composition described herein permits the inclusion of high amounts of further components, including those advantageous in anti-aging compositions. These include vitamin C (e.g., at more than 5 wt%, for example, 10-15 wt%) can improve skin repair while preserving the other properties discussed herein.

[0018] In a particular aspect, the invention relates to a composition comprising the antioxidant system described herein and one or more skin brightening agents. Advantageously, this combination of components may allow for safer cosmetic skin brightening, e.g., by reducing melanin concentrations in the skin but supplementing and / or substituting the beneficial ROS and UVA protection properties of melanin with the antioxidant system described herein. In certain embodiments, the antioxidant system may be selected to provide some skin brightening properties which supplement the effects of the skin brightening agent. For instance, certain ROS agents (e.g., freeROS agents, such as polyphenols) may have a skin brightening effect of their own (e.g., by inhibiting melanin production).

[0019] This application has been drafted into sections. However, the sections should not be read in isolation. Unless otherwise specified, each section is to be read in combination with the other sections i.e. taking the entire application as a whole. This means, for example, that all of the polymers described in the “Polymeric ROS Agent” section are intended to be read in combination with the “UVA Absorption” section (i.e., compositions may contain any of the polymeric ROS agents described herein and have any of the UVA absorption properties described herein). The various optional features can also be combined, even when taken from different parts of the specification. Likewise, all “aspects”, “embodiments”, and “examples” can be combined. No separation of embodiments is intended, unless explicitly stated. Brief Description of the Figures

[0020] Fig.1 is a table reflecting the stain intensities observed before and after washing for certain formulations as described in Example 8.

[0021] Fig.2 is a table listing the properties of certain exemplary formulations as described in Example 12. Detailed Description Definitions

[0022] The following definitions and methods are provided to better define the present invention and to guide those of ordinary skill in the art in the practice of the present invention. Unless otherwise noted, terms are to be understood according to conventional usage by those of ordinary skill in the relevant art.

[0023] As used herein, the term “include”, or grammatical variants thereof, means that certain items belong to a class but the class is not limited to those items. For example, X includes X1, means that the item X1 belongs to the class X, but any number of additional items may also belong to the class.

[0024] As used herein, the term “comprising”, or grammatical variants thereof, encompasses “including” as well as “consisting”. For example, a composition “comprising” X may consist exclusively of X or may contain any number of additional components, e.g., the composition may contain X and Y. “Comprising” also encompasses the term “consisting essentially of”.

[0025] Generally, throughout this application the term “substantially” can mean a deviation of not more than about 25%; particularly not more than about 20%; particularly not more than about 15%; particularly not more than about 10%; most particularly not more than about 5%. For example, the term “substantially” can mean that deviation from a particular value is not more than about 15%.

[0026] As used herein “substantially no organic UV filters” can mean that the concentration and / or number of organic UV filters is limited so as to avoid any significant impact on the SPF of the composition; for example, in some embodiments the concentration and / or number of organic UV filters should not exceed the level required to increase the SPF by 1 SPF unit, relative to a comparative composition lacking said organic UV filters altogether. In more specific embodiments, a composition having “substantially no organic UV filters” has no organic UV filters present.

[0027] Generally, the term “about” can mean a deviation from a particular value of not more than 25%; particularly not more than 20%; particularly not more than 15%; particularly not more than 10%; most particularly not more than 5%. For example, the term “about” can mean that deviation from a particular value is not more than 15%.

[0028] As used herein, the terms “reactive oxygen species” and “ROS” are interchangeable and have their usual meaning in the art. Specifically, these terms may refer to oxygen-containing chemical species comprising one or more unpaired electrons, and / or reactive oxygen-containing compounds without unpaired electrons such as hydrogen peroxide (H2O2) and singlet oxygen species.

[0029] As used herein, the term “polymer” may, in some instances, refer to a specific molecular compound with a precisely defined molecular structure or, in other instances, refer to a population of polymeric molecular compounds with a variable number of repeating units or subunits, and thus a distribution of different sizes (e.g.,because individual polymers within the population may have different numbers of repeating units).

[0030] Molecular masses, molecular weights, and molar masses may be given for various species disclosed herein. In some instances, a molecular mass, molecular weight, or molar mass is given for a particular molecule having a precisely defined chemical structure, in these instances the value given is intended to be a precise value for that molecular species. Accordingly, the molecular weight of non-polymeric compounds, precisely defined oligomeric compounds of uniform structure and size, and polymers of uniform structure and size, is defined and calculated by the molecular structure of the compound. In other instances, a molecular mass, molecular weight, or molar mass is given for molecular species with a variable structure (e.g., a polymer with a variable repeating unit or subunits), in these instances the value is intended to be an average value representative of a population of molecular species having some distribution of values. For example, where a molecular weight is given for a polymer with a variable number of repeating units, the molecular weight is an average molecular weight (e.g., a number average molecular weight or a weight average molecular weight). Accordingly, average molecular weight of such species (e.g., polymers) may be determined by size exclusion chromatography, specifically gel permeation chromatography (GPC), with a monodisperse polystyrene equivalent molecular weight calibration standard and GPC columns (manufactured by PSS (Polymer Standards Service-USA, Inc), applied column combination: SDV 5µm 1000Å, SDV 5µm 500Å, SDV 5µm 100Å). The flow rate in the columns is 1.0 ml / min, eluent: tetrahydrofuran, column temperature: 35°C, a differential refractive index detector (RI) and a UV-detector (254nm) can be used. The dispersibility DISP = (Mw / Mn) is the quotient of molecular weight average and number average and can be calculated from the measurement results. Unless otherwise stated, the average molecular weight is the number average molecular weight.

[0031] As used herein the term “derivative” includes any compound which has been chemically modified without substantially altering its functional character. For example, a derivative may substantially retain one or more characteristic properties of said compound. In particular, derivatives include esters, amides, ethers, sulfides, hydrogenated derivatives, halogenated derivatives, glycosides, and isotopologues.Exemplary derivatives of compounds which are components of the invention may include: alkyl (e.g., C1-C10 alkyl) ethers, heteroalkyl ethers, aryl ethers, and heteroaryl ethers; alkyl (e.g., C1-C10 alkyl) esters and heteroalkyl esters; alkyl (e.g., C1-C10 alkyl) amides and heteroalkyl amides; alkyl (e.g., C1-C10 alkyl) sulfides, heteroalkyl sulfides, aryl sulfides, and heteroaryl sulfides; and glycosides.

[0032] As used herein, the term “E11” refers to a measure of electromagnetic radiation absorbance or extinction at a particular wavelength; normally, the measure is at the wavelength of the absorbance maximum (λmax) of the analyte and the E11 is measured in a solution of an analyte having a concentration of 10 mg / mL with a 1 cm pathlength. Measurement of E11 in the UV range (approximately 290-400 nm) is normally conducted by dissolving the analyte species in a suitable solvent that does not have interfering absorbance in the wavelength range of interest. One suitable solvent is isopropanol. After dissolving the analyte, a dilution with the same solvent is performed so that the maximum absorbance of the solution in a 1 cm pathlength quartz cuvette, measured at room temperature (about 25°C) by a UV / visible spectrophotometer (e.g. Agilent 8453), is in the range of about 0.1 to 1.5 absorbance units. Using the obtained absorbance spectrum and the known concentration of analyte, the absorbance at a concentration of 10 mg / mL is calculated. If not stated otherwise, the E11 result is given for the wavelength at which maximum absorbance occurs. In some cases, a range of wavelengths is given in which the E11 is to be measured and the E11 corresponds to the absorbance or extinction at the maximum of absorbance or extinction within this range.

[0033] The polymeric ROS agent may have an E11 (e.g., in the range of 250 nm to 400 nm) of greater than 50, greater than 100, greater than 200, greater than 300 or greater than 350.

[0034] As used herein, the term “SPF” is an abbreviation for “Sun Protection Factor” and is the internationally standardized measurement of how well a composition protects skin from UVB rays, specifically, of how much more UVB radiation exposure is required to produce sunburn in the presence versus the absence of the composition. SPF measurements can be done in vivo (e.g., on human skin), or in vitro (e.g., on laboratory slides), or by combining in vivo and in vitro methodologies into hybrid tests. Where only one testing methodology is needed, the in vivo SPF rating would be selected. The in vivo SPF rating is determined in clinical trials wherein the compositionis applied to portions of the skin of healthy volunteers and both the composition - protected skin and unprotected skin are irradiated with a solar simulator UV radiation source (e.g., a xenon arc lamp that simulates solar radiation) until they develop minimal erythema, or reddening (i.e., sunburn). The minimal erythema dose (“MED”) is the lowest dose of ultraviolet (UV) radiation (e.g. in units of J / cm2) that produces the first perceptible unambiguous erythema (sunburn) with clearly defined borders filling more than 50% of the exposure site (e.g., a defined rectangle of skin which is exposed to UV radiation), 16 to 24 hours after UV exposure. The SPF rating of a composition is calculated by dividing the MED of the composition-protected skin by the MED of the unprotected skin. For example, in the laboratory setting, skin covered with a composition with an SPF of 50 would be able to endure a UV dose up to fifty times greater without burning than skin without composition. Importantly, though, SPF is not a direct measure of the duration of protection provided during actual sun exposure, because the amount of UVB exposure depends not only on the duration of sun exposure, but also on the intensity of the sun, which varies by time of day (e.g., 8 a.m. vs 2 p.m.), geographical location (e.g., higher vs. lower latitudes), and the presence vs. absence of UVB-absorbing cloud cover. SPF is, however, a useful measure for comparing the amount of UVB protection provided by different compositions.

[0035] As used herein, the term “%UVA-T” is an abbreviation for “percent of UVA transmission” and is used as a measurement of how well a topical composition reduces the amount of UVA radiation reaching the skin. %UVA-T tests can be done in vivo (e.g., on human skin), or in vitro (e.g., on laboratory slides), or by combining in vivo and in vitro methodologies into hybrid tests (e.g., hybrid diffuse reflectance spectroscopy). Where only one testing methodology is needed, the monochromatic hybrid diffuse reflectance spectroscopy (HDRS) %UVA-T rating would be selected. Monochromatic hybrid diffuse reflectance spectroscopy (HDRS) measures the diffuse reflectance spectrum (DRS) of skin with topical sample product in the UVA range and mathematically adjusts the in vitro measurement of the same test sample to match the in vivo DRS in the range of the hybridization wavelengths. Subjects for HDRS testing have skin individual typology angle (ITA) between 28° and 70°. About 2 mg / cm2 of sample product or standard (e.g., Sunscreen Standard P5, which is a composition comprising (by weight) water (50.35%), disodium EDTA (0.05%), methylparaben(0.35%), chlorphenesin (0.2%), phenoxyethanol (0.7%), glycerin (5%), xanthan gum (0.01%), butyl methoxydibenzoylmethane (3%), octocrylene (10%), ethylhexylsalicylate (5%), benzophenone-3 (5%), PPG-2 myristyl ether propionate (2%), octyldodecyl neopentanoate (2%), butyloctyl salicylate (8%), PVP / eicosane copolymer (1.3%), polyglceryl-3 methyl glucose distearate (2%), cetyl alcohol (0.5%), stearic acid (1%), butylparaben (0.03%), cyclopentasiloxane (3%), acrylates / C10-30 alkyl acrylates crosspolymer (0.2%), triethanolamine (0.06%), potassium cetyl phosphate (0.25%)) is applied and distributed evenly over an area of about 36 cm2and allowed to dry for about 15 minutes. A double monochromator system is used in synchronous scan mode to record the diffuse reflectance spectrum of skin coated with the test sample illuminated with a xenon lamp. The in vitro spectrum of the test product is recorded on roughened PMMA plates (e.g., as described in ISO 24443, and summarized below). The in vitro absorbance spectrum recorded prior to UV irradiation (pre-irradiation spectrum) may be used to calculate the pre-irradiation HDRS result. More commonly, the change in absorbance observed before and after UV irradiation during in vitro testing is used to adjust the initial DRS spectrum by determining the spectral ratio of photodegradation (SRPD). The SRPD-adjusted DRS spectrum is subsequently used to determine the hybridization wavelengths and to calculate the hybrid DRS spectrum from which %UVA-T can be calculated. %UVA-T is the average percent transmission of the hybrid DRS spectrum of the UVA wavelengths (320 – 400 nm). %UVA-T is determined in vitro by measuring the absorbance of UV radiation through polymethyl methacrylate (PMMA) plates (5 cm x 5 cm, roughed either by a molding process or sandblasting). A blank PMMA plate is prepared by coating the plate with a thin layer of glycerin, and the blank absorbance spectrum is recorded. Next, multiple PMMA plates are coated with the composition, about 1.2 – 1.3 mg / cm2depending on PMMA plate type. The application of the test composition is performed first using circular motions followed by vertical and horizontal strokes, over the course of about 1 minute total. The plates are then allowed to dry at about 30°C. The blank-corrected UV absorbance spectrum of each plate is recorded using a suitable spectrometer and an initial in vitro %UVA-T value (average transmission between 320 – 400 nm) for each sample plate is calculated. The sample plates are subsequently exposed to 36 J / cm2 of solar simulator radiation and the %UVA-T is re-measured to yield the final %UVA-T result. The final%UVA-T result is the average transmission of the UV-irradiated sample plates over the wavelengths 320 – 400 nm.

[0036] As used herein, the term “UVA-PF” is an abbreviation for “UVA Protection Factor” and is used as a measurement of how well a composition protects the skin from UVA radiation. UVA-PF tests are performed in a similar manner to SPF tests for UVB radiation and can be done in vivo (e.g., on human skin), or in vitro (e.g., on laboratory slides), or by combining in vivo and in vitro methodologies into hybrid tests (e.g., hybrid diffuse reflectance spectroscopy). Where only one testing methodology is needed, the monochromatic hybrid diffuse reflectance spectroscopy (HDRS) UVA-PF rating would be selected. Hybrid diffuse reflectance spectroscopy (HDRS) measures the diffuse reflectance spectrum (DRS) of skin with topical sample product in the UVA range and mathematically adjusts the in vitro measurement of the same test sample to match the in vivo DRS in the range of the hybridization wavelengths. Subjects for HDRS testing have skin individual typology angle (ITA) between 28° and 70°. About 2 mg / cm2of sample product or standard (e.g., Sunscreen Standard P5, which is a composition comprising (by weight) water (50.35%), disodium EDTA (0.05%), methylparaben (0.35%), chlorphenesin (0.2%), phenoxyethanol (0.7%), glycerin (5%), xanthan gum (0.01%), butyl methoxydibenzoylmethane (3%), octocrylene (10%), ethylhexylsalicylate (5%), benzophenone-3 (5%), PPG-2 myristyl ether propionate (2%), octyldodecyl neopentanoate (2%), butyloctyl salicylate (8%), PVP / eicosane copolymer (1.3%), polyglceryl-3 methyl glucose distearate (2%), cetyl alcohol (0.5%), stearic acid (1%), butylparaben (0.03%), cyclopentasiloxane (3%), acrylates / C10-30 alkyl acrylates crosspolymer (0.2%), triethanolamine (0.06%), potassium cetyl phosphate (0.25%)) is applied and distributed evenly over an area of about 36 cm2and allowed to dry for about 15 minutes. A double monochromator system is used in synchronous scan mode to record the diffuse reflectance spectrum of skin coated with the test sample illuminated with a xenon lamp. The in vitro spectrum of the test product is recorded on roughened PMMA plates (e.g., as described in ISO 24443). The in vitro absorbance spectrum recorded prior to UV irradiation (pre-irradiation spectrum) may be used to calculate the pre-irradiation HDRS result. More commonly, the change in absorbance observed before and after UV irradiation during in vitro testing is used to adjust the initial DRS spectrum by determining the spectral ratio of photodegradation (SRPD). The SRPD-adjusted DRS spectrum is subsequently used to determine the hybridization wavelengths and to calculate the hybrid DRS spectrum from which SPF and UVA-PF are calculated. Accordingly, the UVA-PF may be calculated as described in ISO 24443, e.g., as the ratio of the integrated effective irradiance of the source (which is equal to radiation source spectrum multiplied by the corresponding action spectrum) to the integral of the transmitted effective irradiance (which is equal to radiation source spectrum multiplied by the corresponding action spectrum multiplied by transmission at each wavelength). In vivo UVA-PF tests are performed on human volunteers with skin types that tan but do not burn (usually, darker skin types). A controlled amount of sunscreen is applied to selected portions of volunteers’ skin and small incremental doses of UVA radiation are applied to the protected portions and to an unprotected portion of skin. A tanning reaction known as Persistent Pigment Darkening (PPD) develops 3-6 hours after exposure on those portions of skin that have received more UVA exposure than the UVA protection provided by the sunscreen or inherent in the unprotected skin. The UVA-PF of the tested sunscreen is calculated, similarly to SPF, by dividing the accumulated Joules / sqm of light exposure that causes slight but clearly visible persistent pigment darkening of the protected skin divided by the accumulated Joules / sqm of light exposure causing slight but clearly visible persistent pigment darkening of the unprotected skin. UVA-PF is determined in vitro by measuring the absorbance of UV radiation through Polymethyl methacrylate (PMMA) plates (5 cm x 5 cm, roughed either by a molding process or sandblasting). A blank PMMA plate is prepared by coating the plate with a thin layer of glycerin, and the blank absorbance spectrum is recorded. Next, multiple PMMA plates are coated with sunscreen product, about 1.2 – 1.3 mg / cm2depending on PMMA plate type. The application of sunscreen is performed first using circular motions followed by vertical and horizontal strokes, over the course of about 1 minute total. The plates are then allowed to dry at about 30°C. The blank-corrected UV absorbance spectrum of each plate is recorded using a suitable spectrometer and an initial in vitro UVA-PF value for each sample plate is calculated, considering the experimental absorbance spectrum, the PPD action spectrum, and solar simulator radiation spectrum. The sample plates are subsequently exposed to about 36 J / cm2 of solar simulator radiation and the UVA-PF is re-measured to yield the final UVA-PF result. Another example of a hybrid method for determining the UVA-PF of a sunscreen formulation is the ISO 24443 / COLIPA method and is performed similarly tothe aforementioned in vitro UVA-PF determination, but incorporates a known in vivo SPF result. In this method, a scalar value “C” is determined for each in vitro SPF value in order to adjust the in vitro SPF result to match the SPF experimentally determined by in vivo testing of that sunscreen product (thus combining in vivo and in vitro methodologies to yield a hybrid result). Using the “C” value, the initial (pre-irradiation) in vitro UVA-PF is calculated before UV irradiation. The UV exposure dose is calculated as 1.2 J / cm2times the initial UVA-PF result up to a maximum of 36 J / cm2, and is used to account for any photo-instability of the product. The sample plates are exposed to UV radiation to achieve the exposure dose in a suitable solar simulator at controlled temperature, and then their absorbance spectra are re-measured. The final UVA-PF is calculated from the sample PMMA plate absorbance spectra following UV irradiation. As used herein, the term “ROS inhibition” refers to the action of preventing or reducing generation of ROS. More specifically, the term “ROS inhibition” may refer to the action of reducing the amount of UV-generated ROS upon exposure of a sample to UV radiation (e.g., UVA radiation). The ROS inhibition capacity of a compound or mixture of compounds may be expressed in terms of the concentration of said compound or mixture of compounds resulting in a 50% reduction in the change (e.g., loss or gain) of absorbance or fluorescence at the characteristic wavelength of a suitable monitoring species (e.g., p-nitrosodimethylaniline or nitroblue tetrazolium, as described below, or 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) , thiobarbituric acid, 2′,7′-dichlorofluorescin diacetate, or copper(II)-neocuproine) relative to a control experiment (e.g., without any test compound present), and this concentration may be referred to as an “ROS inhibition IC50”. One method for measuring the ROS inhibition IC50 involves measurement of singlet oxygen formation under UV irradiation which is monitored by loss of p-nitrosodimethylaniline absorbance and another method involves measurement of superoxide formation under UV irradiation which is monitored by gain of nitroblue tetrazolium absorbance, for example as set out below. Where only one method is needed, the singlet oxygen formation assay using p-nitrosodimethylaniline (RNO) would be selected. - Singlet oxygen formation (and potentially other radical species) may be monitored by loss of absorbance of p-nitrosodimethylaniline (RNO) in the presence of imidazole (IMD). IMD is used to convert singlet oxygen species intoperoxide (IMD transannular peroxide intermediate), while RNO may also scavenge hydroxyl radicals directly (if present). Absorbance of 440 to 490 nm (which is characteristic of RNO) is reduced as nitrosodimethylaniline is converted to nitrodimethylaniline. Photogeneration of reactive oxygen species such as singlet oxygen may be accomplished with known photosensitizers, such as quinine, titanium dioxide particles (e.g. P25), or photoinitiators such as 4,4′- Bis(dimethylamino)benzophenone. Where only one photosensitizer is required, quinine can be selected. Exposure of the photosensitizer to UV radiation mimicking that of the solar spectrum (solar simulator radiation) generates reactive oxygen species (ROS) such as singlet oxygen. Typical assay conditions include dissolution of Quinine, IMD, RNO at 200 µM, 10 mM, and 20 µM respectively in in 20% DMSO and 80% 10mM citrate or phosphate buffer at pH 7 or 7.4. The compound(s) to be tested is( / are) added at a range of different concentrations (e.g., between 0.5 and 50 µM). The sample solution, commonly in a multiwell plate (without lid or with UV-transparent lid) or sealed quartz cuvette, is exposed to UV irradiation. The UV radiation source may be a solar simulator (e.g. Atlas CPS+), a UVA source, or a UVB source. Irradiation conditions should ensure that RNO absorbance of control experiments is almost or completely eliminated. Typical irradiation conditions using a solar simulator are about 7.5 mW / cm2UV for 30 minutes in a solar simulator (Atlas CPS+) with temperature controlled to 30-40 °C. After UV exposure, about 30 volume % of alcohol (e.g. isopropanol) is added to each sample volume, and the absorbance in the range of 440-490 nm is recorded. The amount of ROS inhibition owing to the test compound(s) are determined against controls containing only photosensitizer and RNO / IND. Hence, the concentration of test compound resulting in a 50% reduction in the loss of absorbance for a suitable wavelength in the range of 440-490 nm may be determined (i.e. the ROS inhibition IC50). - Superoxide formation may be monitored by an increase of absorbance upon reduction of nitroblue tetrazolium (NBT). NBT is reduced by superoxide radicals resulting in a color change from pale yellow to a blue formazan product. A UV photosensitizer may be used as the superoxide generating source, such as quinine or titanium dioxide particles (e.g. P25). Exposure of the photosensitizerto UV radiation, such as a UV source mimicking the solar spectrum (solar simulator radiation) generates reactive oxygen species (ROS) such as superoxide. Typical assay conditions include dissolution of Quinine at 200 µM and NBT at 50 µM in 80% 10 mM carbonate buffer at pH 9 and 20% DMSO. The compound(s) to be tested is( / are) added at a range of different concentrations (e.g., between 0.5 and 50 µM). The sample solution, commonly in a multiwell plate (without lid or with UV-transparent lid) or sealed quartz cuvette, is exposed to UV irradiation. The UV radiation may be solar simulated radiation (e.g. Atlas CPS+), a UVA source, or a UVB source. UV irradiation conditions should be selected such that the NBT is nearly or completely converted following the UV exposure. Typical UV irradiation conditions with a solar simulator are about 7.5 mW / cm2 UV for 10 minutes in a solar simulator (Atlas CPS+) with temperature controlled to 30-40C. After UV exposure, the sample volume is increased by 20% by addition of organic solvent (e.g. isopropanol or DMSO) and 10% volume of 2M sodium hydroxide is added. The absorbance between 500 and 700 nm is recorded. The amount of ROS inhibition owing to test compound(s) is determined against controls containing only photosensitizer and NBT. The concentration of test compound resulting in a 50% reduction in the gain of absorbance at a suitable wavelength between 500 and 700 nm may be determined (i.e., the ROS inhibition IC50). Alternative methods of measuring ROS inhibition include: - Calculating a ratio between the magnitudes of change in the amount of a monitoring species following UV exposure of a sample with ROS inhibitor and control (without ROS inhibitor). This mode is useful for situations where the ROS inhibitor is in a separate phase than the monitoring species (e.g. the ROS inhibitor is deposited as a film and the monitoring species is in solution, or the ROS inhibitor is in solution and the monitoring species is in a film or entrapped within a membrane). - In situations where an ROS inhibitor is entirely insoluble or incorporated into a formulation, the sample may be applied to a suitable UV-transparent substrate such as quartz, poly(methy methacrylate), or skin-mimic substrates such as Vitro-Skin. Typical application concentrations are about 2 mg / cm2for aformulation or about 0.1-0.4 mg / cm2of a pure ingredient in a volatile liquid. Concentrations of RNO / IMD or NBT assay reagents, buffers and solvents remain the same as described above. The sample or control (without ROS inhibitor) film is positioned between the UV radiation source and monitoring species solution (preferably just above the surface of the solution) and exposed to UV irradiation from a solar simulator, UVA source, or UVB source. UV irradiation conditions are selected such that control experiments without ROS inhibitor nearly or completely reach their endpoint. Typical UV irradiation conditions with a solar simulator are about 7.5 mW / cm2 UV for 10-60 minutes in a chamber with temperature controlled to 30-40 °C. The ROS inhibition ratio is calculated as the magnitude of change of the monitoring species in a control experiment divided by the change with sample.

[0037] As used herein, the term “ROS inhibitor” refers to a chemical species which prevents or reduces generation of ROS. In particular, an “ROS inhibitor” may be any chemical (optionally, molecular) species having an absorption maximum for ultraviolet radiation in the wavelength range of from 250 nm to 400 nm; and an E11 of at least 50 for ultraviolet radiation in the wavelength range of from 250 nm to 400 nm. Alternatively, or in addition, an ROS inhibitor can be any polymeric ROS agent as defined elsewhere herein.

[0038] As used herein, the term “ROS capture” may refer to the antioxidant activity of a compound, or more specifically to the action of chemically reducing or oxidising ROS species. ROS capture may be determined by a number of known assays for measuring antioxidant capacity, the most common of which is the 2,2-diphenyl-1- picrylhydrazyl (DPPH) assay. DPPH forms a stable radical when dissolved in certain organic solvents, such as alcohols or acetonitrile. The radical is resonance stabilized, and the compound has absorbance at about 520 nm. Hydrogen transfer from an antioxidant (e.g. phenolic) or electron transfer from a radical species reduces the DPPH molecule to a hydrazine, resulting in loss of absorbance at 520 nm. The DPPH assay is a rapid and effective way to evaluate the ROS capture activity of many compounds. In a typical DPPH antioxidant capacity assay, about 3 mL of 60 µM DPPH in 40% alcohol (e.g. isopropanol) and 60% acetate buffer pH 5.5 is combined with 100 uL of antioxidant sample or blank (e.g. isopropanol), and left to react in the dark for 30 minutes beforerecording absorbance at 517 nm. The volumes used may be scaled to the experimental conditions required. Earlier time points may also be recorded to evaluate the kinetics of radical scavenging. Trolox may be used to generate a calibration curve, typically in the range of 10 to 90 nmoles (100 uL of solutions containing 100 to 900 µM Trolox). The results of the assay may be reported in trolox-equivalent antioxidant capacity (TEAC) or by determining the concentration of test compound required to reduce the loss of absorbance at 517 nm by 50% (i.e., the ROS capture IC50). Where only one parameter is needed, the ROS capture IC50 can be selected. An alternative assay involves 2,2′- Azino-bis(3-ethylbenzothiazoline-6-sulfonic cation radical (ABTS) reduction which is performed by mixing ABTS and potassium persulfate at 7mM and 2.45 mM respectively for at least 12 hours in the dark at room temperature. Subsequently 10 mM of phosphate buffer pH 7.4 is added to the ABTS radical solution to achieve an absorbance of about 0.7. Portions of this solution are added to test or control antioxidants in a suitable solvent. The mixtures are allowed to react in the dark for at least 6 minutes before the absorbance at about 734 nm is recorded. The results of the assay may be reported in trolox-equivalent antioxidant capacity (TEAC) or by determining the concentration of antioxidant required to reduce the loss of absorbance at 734 nm by 50% (i.e. the ROS capture IC50). The ABTS assay may provide more reliable results for weaker antioxidants, as compared to the DPPH assay. Accordingly, where only one assay is required the ABTS assay may be selected for its broad applicability.

[0039] As used herein, the term “ROS capturer” refers to a chemical species having antioxidant activity, or more specifically a chemical (optionally, molecular) species capable of chemically reducing or oxidising ROS species. In particular, an “ROS capturer” may be any chemical (optionally, molecular) species having an ROS capture IC50 of 10 mM or less. Alternatively, or in addition, an ROS inhibitor can be any free ROS agent as defined elsewhere herein.

[0040] As used herein, the term “dual-functional ROS agent” refers to a single chemical (optionally, molecular) species which is both an ROS capturer and an ROS inhibitor. Accordingly, an antioxidant system comprising an “ROS capturer” and “ROS inhibitor” may refer to an antioxidant system comprising a single chemical species which is both the ROS capturer and ROS inhibitor; or it may refer to an antioxidant systemcomprising a chemical species which is an ROS capturer and a different chemical species which is an ROS inhibitor. In certain embodiments, the antioxidant system comprises a “ROS capturer” and “ROS inhibitor” because the system comprises a chemical (optionally, molecular) species which is both an ROS capturer and an ROS inhibitor (i.e. the system comprises a dual-functional ROS agent). In certain embodiments, the antioxidant system comprises a “ROS capturer” and “ROS inhibitor” because the system comprises a chemical species which is an ROS capturer and a different chemical species which is an ROS inhibitor. In some embodiments, the preceding two embodiments also include further ROS capturer, ROS inhibitor and / or dual-functional ROS agents.

[0041] As used herein, the term “naturally occurring antioxidant” means any compound or substance which has antioxidant properties (e.g., a compound or substance which is an ROS capturer and / or an ROS inhibitor); and is produced by a living organism (e.g., a plant). Naturally occurring antioxidants for use in accordance with the invention can be of natural origin (i.e., having been produced by a living organism prior to use in the invention) or can be of synthetic origin (i.e., they may be natural products which exist in nature but have been synthesised by an industrial process for use in the invention). Naturally occurring antioxidants may include naturally occurring polyphenols and carotenoids. Some particular examples of naturally occurring antioxidants are quercetin, naringenin, mangiferin, luteolin, hesperidin, and apigenin.

[0042] As used herein, the term “organic UV filter” may refer to any compound from the list consisting of 1-(4-Methoxyphenyl)-3-(4-tert-butylphenyl)-1,3-propanedione, tris-biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl-N,N-dimethylammonium)-2- hydroxypropane-1-sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3-phenylprop-2-enoate, 2-ethylhexyl 2- cyano-3,3-diphenylprop-2-enoate, hexyl 2-[4-(diethylamino)-2- hydroxybenzoyl]benzoate, 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino)benzoate, 2-phenyl-3H-benzimidazole-5-sulfonic acid, 2-ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4-methoxyphenyl)(2- hydroxyphenyl)methanone, (2-hydroxy-4-methoxyphenyl)(phenyl)methanone, 3,3,5- trimethylcyclohexyl 2-hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2-ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2-hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2-hydroxy- N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4-[(Z)-[7,7- Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3-benzotriazol- 2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4-methoxyphenyl)-1,3,5-triazine-2,4- diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3- benzimidazole-4-sulfonate), 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3- tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2- ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine-2,4- diyl)bis(azanediyl)]dibenzoate, and 3-Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2- enoate, or a salt of any of the aforementioned.

[0043] The term “acrylic” as used herein, alone or as part of another group, denotes X4OC(O)CH=CH- wherein X4 is hydrogen, optionally substituted hydrocarbyl, or heterocyclo. Exemplary optionally substituted hydrocarbyl includes optionally substituted alkyl such as optionally substituted methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, 2-ethylhexyl, and tridecyl. By way of further example optionally substituted alkyl includes alkoxymethyl and acylmethyl.

[0044] The term “acrylamide” as used herein, alone or as part of another group, denotes X8X9NC(O)CH=CH- wherein X8 and X9 are independently hydrogen or optionally substituted alkyl or other optionally substituted hydrocarbon, or X8 and X9 taken together with the nitrogen atom to which they are attached form an optionally substituted heterocyclic moiety, each as defined in connection with such term, typically having from 3 to 8 atoms in the ring. Exemplary alkyl include methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl and octyl and exemplary substituted alkyl include alkoxyalkyl and acylalkyl.

[0045] The term "acyl," as used herein alone or as part of another group, denotes the moiety formed by removal of the hydroxyl group from the carboxy group, -COOH, of an organic carboxylic acid, e.g., X4C(O)-, wherein X4 is X1, X1O-, X1X2N-, or X1S-, X1ishydrogen, optionally substituted hydrocarbyl, or heterocyclo, and X2is hydrogen, hydrocarbyl, substituted hydrocarbyl or heterocyclo. In certain embodiments, X1and X2are independently optionally substituted alkyl, optionally substituted alkenyl, aryl, or heterocyclo. Exemplary acyl moieties include acetyl, propionyl, benzoyl, pyridinylcarbonyl, and the like.

[0046] The term "acylalkyl," as used herein, alone or as part of another group, denotes an alkyl group as described herein substituted by an acyl group as defined herein (e.g., -(alkyl)-C(O)X4 radical wherein X4 is as defined in connection with the term “acyl”). Exemplary alkyl include methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl and octyl.

[0047] The term "acyloxy," as used herein, alone or as part of another group, denotes an acyl group as described herein bonded through an oxygen linkage (-O-), e.g., X4C(O)O-, wherein X4 is as defined in connection with the term "acyl."

[0048] The terms "alicyclic", "alicyclo" and "alicyclyl" as used herein, alone or as part of another group, are used interchangeably and denote a saturated monocyclic group of 3 to 8 carbon atoms and includes cyclopentyl, cyclohexyl, cycloheptyl, and the like.

[0049] The term "aliphatic" denotes saturated and non-aromatic unsaturated hydrocarbyl moieties having, for example, one to about twenty carbon atoms or, in specific embodiments, one to about twelve carbon atoms, one to about ten carbon atoms, one to about eight carbon atoms, or even one to about four carbon atoms. The aliphatic groups include, for example, alkyl moieties such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl and the like, and alkenyl moieties of comparable chain length.

[0050] The term "alkanol" as used herein, alone or as part of another group, denotes an alkyl moiety that has been substituted with at least one hydroxyl group.

[0051] The terms "alkaryl" and "alkylaryl," as used herein, alone or as part of another group, are used interchangeably and denote an -(aryl)-X11 radical, (e.g., a phenyl group substituted by X11) wherein X11 is as defined in connection with the term "alkyl.”

[0052] The term "alkenoxy," as used herein, alone or as part of another group, denotes an -OX6 radical, wherein X6 is as defined in connection with the term "alkenyl." Exemplary alkenoxy moieties include ethenoxy, propenoxy, butenoxy, hexenoxy, and the like.

[0053] The term "alkenyl" as used herein, alone or as part of another group, denotes linear, branched or cyclic carbon radicals having at least one carbon-carbon double bond. The term "alkenyl group" can encompass conjugated and non-conjugated carbon-carbon double bonds or combinations thereof. An alkenyl group, for example and without being limited thereto, can encompass two to about twenty carbon atoms or, in a particular embodiment, two to about twelve carbon atoms. In certain embodiments, alkenyl groups are "lower alkenyl" groups having two to about six carbon atoms. Examples of alkenyl groups include, but are not limited thereto, ethenyl, propenyl, allyl, vinyl, butenyl and 4-methylbutenyl. The terms "alkenyl group" and "lower alkenyl group", encompass groups having "cis" or "trans" orientations, or alternatively, "E" or "Z" orientations.

[0054] The term "alkoxy," as used herein alone or as part of another group, denotes an -OX5 radical, wherein X5 is as defined in connection with the term "alkyl." Exemplary alkoxy moieties include methoxy, ethoxy, propoxy, or 2-propoxy, n-, iso-, or tert-butoxy, cyclohexyloxy and the like.

[0055] The term “alkoxyalkyl” as used herein, alone or as part of another group, denotes a linear monovalent hydrocarbon radical of one to twenty, or, in specific embodiments, one to about twelve carbon atoms substituted with at least one alkoxy group, such as one or two alkoxy groups, or a branched monovalent hydrocarbon radical of three to twenty carbons substituted with at least one alkoxy group, such as one or two alkoxy groups, as defined herein, e.g., 2-methoxyethyl, 1-, 2-, or 3- methoxypropyl, 2-ethoxyethyl, and the like.

[0056] The term “alkoxyaryl” as used herein, either alone or within other terms, denotes an aryl group substituted by at least one alkoxy group, as defined herein.

[0057] The term “alkoxycarbonyl” as used herein, alone or as part of another group, denotes a -C(O)OR radical where R is alkyl as defined herein, e.g., methoxycarbonyl, ethoxycarbonyl, and the like.

[0058] The term "alkyl" as used herein, alone or as part of another group, denotes saturated linear, branched or cyclic carbon radicals having, for example, one to about twenty carbon atoms or, in specific embodiments, one to about twelve carbon atoms. In certain embodiments, alkyl groups are "lower alkyl" groups having one to about six carbon atoms. Examples of such groups include, but are not limited thereto, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl and the like. In more specific embodiments, lower alkyl groups have one to four carbon atoms.

[0059] The term "alkylamino group" as used herein, alone or as part of another group, denotes amino groups directly attached to the remainder of the molecule via the nitrogen atom of the amino group and wherein the nitrogen atom of the alkylamino group is substituted by one or two alkyl groups. In some embodiments, alkylamino groups are "lower alkylamino" groups having one or two alkyl groups of one to six carbon atoms, attached to a nitrogen atom. In other embodiments, lower alkylamino groups have one to three carbon atoms. Suitable "alkylamino" groups may be mono or dialkylamino such as N-methylamino, N-ethylamino, N,N-dimethylamino, N,N- diethylamino, pentamethyleneamine and the like.

[0060] The term “alkylcarbonyl” as used herein, alone or as part of another group, denotes a -C(O)R radical where R is alkyl as defined herein, e.g., methylcarbonyl, ethylcarbonyl, and the like.

[0061] The term “alkylene” as used herein, alone or as part of another group, denotes a linear saturated divalent hydrocarbon radical of one to twenty carbon atoms, or, in specific embodiments, one to about twelve six carbon atoms or a branched saturated divalent hydrocarbon radical of three to twenty carbon atoms unless otherwise stated, e.g., methylene, ethylene, propylene, 1-methylpropylene, 2-methylpropylene, butylene, pentylene, and the like.

[0062] The terms "amido" and "amide," as used herein, alone or as part of another group, are used interchangeably and denote a group having the formula – C(O)N(X8)(X9), wherein X8 and X9 are as defined in connection with the terms "amine" or "amino." For example, "substituted amide" refers to a group of formula – C(O)N(X8)(X9), wherein at least one of X8 and X9 are other than hydrogen and“unsubstituted amido," for example, refers to a group of formula –C(O)N(X8)(X9) wherein each of X8 and X9 are hydrogen.

[0063] The terms "amine" and "amino" as used herein, alone or as part of another group, are used interchangeably and denote a group of formula *-N(X8)(X9), wherein * denotes the point of attachment of the moiety to the remainder of the molecule and X8and X9are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl, heteroaryl, or heterocyclo, or X8 and X9 taken together form a substituted or unsubstituted alicyclic, aryl, or heterocyclic moiety, each as defined in connection with such term, typically having from 3 to 8 atoms in the ring. "Substituted amine," for example, refers to a group having the formula -N(X8)(X9), wherein at least one of X8 and X9 are other than hydrogen and “unsubstituted amine” refers to a group having the formula -N(X8)(X9), wherein each of X8 and X9 are hydrogen.

[0064] The term "aminoalkyl group" as used herein, alone or as part of another group, denotes linear or branched alkyl groups having one to about twenty carbon atoms, or, in specific embodiments, one to about twelve carbon atoms, any one of which may be substituted with one or more amino groups, directly attached to the remainder of the molecule via an atom other than a nitrogen atom of the amine group(s). In some embodiments, the aminoalkyl groups are "lower aminoalkyl" groups having one to six carbon atoms and one or more amino groups. Examples of such groups include aminomethyl, aminoethyl, aminopropyl, aminobutyl and aminohexyl.

[0065] The term "ammonium" as used herein, alone or as part of another group, are used interchangeably and denote a group of formula *-N+(X8)(X9)(X10), wherein * denotes the point of attachment of the moiety to the remainder of the molecule and X8, X9 and X10 are independently hydrogen, hydrocarbyl, or substituted hydrocarbyl, heteroaryl, or heterocyclo, or X8 and X9 taken together form a substituted or unsubstituted alicyclic, aryl, or heterocyclic moiety, each as defined in connection with such term, typically having from 3 to 8 atoms in the ring.

[0066] The term "ammoniumalkyl" as used herein, alone or as part of another group, are used interchangeably and denote a group of formula *-(alkyl)-N+(X8)(X9)(X10), wherein * denotes the point of attachment of the moiety to the remainder of themolecule, alkyl is as previously defined, and X8, X9 and X10 are as defined in connection with the term “ammonium.”

[0067] The term “aralkenyl” as used herein, alone or as part of another group, denotes an alkenyl radical, as defined herein, substituted with an optionally substituted aryl group, as defined herein.

[0068] The term "aromatic group" as used herein, alone or as part of another group, includes “aryl” and “heteroaryl” groups as defined herein.

[0069] The terms "aryl group" and “Ar” as used herein, alone or as part of another group, are used interchangeably and denote an aromatic group having one or more rings wherein such rings may be attached together in a pendent manner or may be fused. In particular embodiments, an aryl group comprises one, two or three rings. Typical polycyclic aryl groups have two or three rings. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, acenaphthyl and anthracenediylidene.

[0070] The term “arylalkyl” as used herein, alone or as part of another group, denotes an alkyl radical, as defined herein, substituted with an aryl group, as defined herein. For example, -CH2-Ar wherein the aryl group is optionally substituted with one or more acyl, acyloxy, alkoxycarbonyl, alkyl, heterocyclo, or hydroxyl groups.

[0071] The term “arylamino” as used herein, alone or as part of another group, denotes a *-N(X8)(X9) radical wherein * denotes the point of attachment of the moiety to the remainder of the molecule and X8 and X9 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroaryl, or heterocyclo, provided that at least one of X8 and X9 is aryl as defined herein.

[0072] The term “aryloyl” as used herein, alone or as part of another group, denotes a -C(O)R radical where R is optionally substituted aryl as defined herein. Examples of optionally substituted aryloyl groups include optionally substituted benzoyl groups.

[0073] The terms “carbocyclic,” “carbocycle” and “carbocyclyl” as used herein alone or as part of another group, are used interchangeably and denote any mono-, bi-, or tricyclic ring system in which the ring atoms are exclusively carbon and the ring system contains at least one aliphatic carbon-carbon bond. For example, thecarbocycle may be cyclohexane, cycloheptane, and norbornane. Unless specified otherwise, the carbocyclic group may be substituted at one or more ring positions as described for heterocycles. The terms "carbocycle" and "aryl" are mutually exclusive.

[0074] The term "carboxy" as used herein, alone or as part of another group denotes -COOH.

[0075] The term "cyano," as used herein, alone or as part of another group, denotes a group of formula –C N.

[0076] The term "cycloalkyl," as used herein, alone or as part of another group, denotes a cyclic saturated monovalent bridged or non-bridged hydrocarbon radical of three to ten carbon atoms. Exemplary cycloalkyl moieties include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, adamantyl and bicyclo[2.2.1]heptyl. Unless specified otherwise, the cycloalkyl group may be substituted at one or more ring positions with hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkoxy, acyl, acyloxy, amino, aryloxy, carboxy, cyano, halogen, mercapto, oxo, nitro, thiol, sulfo, and the salts thereof.

[0077] The term "cycloalkenyl," as used herein, alone or as part of another group, denotes a cyclic, non-aromatic, monovalent bridged or non-bridged hydrocarbon radical of three to ten carbon atoms containing at least one unsaturated carbon-carbon bond. Unless specified otherwise, the cycloalkyl group may be substituted at one or more ring positions with hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkoxy, acyl, acyloxy, amino, aryloxy, carboxy, cyano, halogen, mercapto, oxo, nitro, thiol, sulfo, and the salts thereof.

[0078] The term "halo" as used herein, alone or as part of another group, denotes halogen atoms such as fluorine, chlorine, bromine or iodine atoms.

[0079] The term "haloalkyl group" as used herein, alone or as part of another group, denotes groups wherein any one or more of the alkyl carbon atoms is substituted with halo as defined herein. Specifically encompassed are monohaloalkyl, dihaloalkyl and polyhaloalkyl groups including perhaloalkyl. A monohaloalkyl group, for example, may have either an iodo, bromo, chloro or fluoro atom within the group. Dihalo and polyhaloalkyl groups may have two or more of the same halo atoms or a combination of different halo groups. "Lower haloalkyl group" encompasses groups having 1-6 carbonatoms. In some embodiments, lower haloalkyl groups have one to three carbon atoms. Examples of haloalkyl groups include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl.

[0080] The term "heteroaliphatic" as used herein, alone or as part of another group, denotes a chain of 1 to 25 carbon atoms, typically 1 to 12 carbon atoms, more typically 1 to 10 carbon atoms, and most typically 1 to 8 carbon atoms, and in some embodiments 1 to 4 carbon atoms that can be saturated or unsaturated (but not aromatic), containing one or more heteroatoms, such as halogen, oxygen, nitrogen, sulfur, phosphorus, or boron. A heteroatom atom may be a part of a pendant (or side) group attached to a chain of atoms (e.g., *-CH(OH)CH(NH2)-* wherein * denotes the point of attachment to the remainder of the moiety and the carbon atom is a member of a chain of atoms) or it may be one of the chain atoms (e.g., -ROR- or -RNHR- where each R is aliphatic). Heteroaliphatic encompasses heteroalkyl and heterocyclo but does not encompass heteroaryl.

[0081] The term "heteroalkyl" as used herein, alone or as part of another group, denotes a fully saturated heteroaliphatic moiety.

[0082] The term “heterocycloalkyl” as used herein, alone or as part of another group, denotes a heterocycle group as defined herein covalently bonded to an alkyl group as defined herein (e.g., *-CH2-HET wherein * denotes the point of attachment of the heterocycloalkyl moiety to the remainder of the moiety and “HET” is the heterocyclo moiety).

[0083] The terms “heteroaryl” and “heteroaromatic” as used herein, alone or as part of another group, are used interchangeably and denote any mono-, bi-, or tricyclic aromatic ring system having the number of atoms designated where at least one ring is a 5-, 6- or 7-membered ring containing from one to four heteroatoms selected from the group nitrogen, oxygen, and sulfur, and in a particular embodiment at least one heteroatom is nitrogen. In one example, the heteroaryl is a five to six membered aromatic ring containing one, two or three heteroatoms selected from nitrogen, oxygen and sulfur. Included in the definition are any bicyclic groups where any of the aboveheteroaryl rings are fused to a benzene ring. Particular heteroaryls incorporate a nitrogen or oxygen heteroatom. The following ring systems are examples of the heteroaryl (whether substituted or unsubstituted) groups denoted by the term “heteroaryl”: thienyl, furyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, thiatriazolyl, oxatriazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, thiazinyl, oxazinyl, triazinyl, thiadiazinyl, oxadiazinyl, dithiazinyl, dioxazinyl, oxathiazinyl, tetrazinyl, thiatriazinyl, oxatriazinyl, dithiadiazinyl, imidazolinyl, dihydropyrimidyl, tetrahydropyrimidyl, tetrazolo[1,5-b]pyridazinyl and purinyl, as well as benzo-fused derivatives, for example benzoxazolyl, benzofuryl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, benzoimidazolyl and indolyl. A particular “heteroaryl” may be selected from: 1,3-thiazol-2-yl, 4-(carboxymethyl)-5- methyl-1,3-thiazol-2-yl, 4-(carboxymethyl)-5-methyl-1,3-thiazol-2-yl, 1,2,4-thiadiazol-5- yl, 3-methyl-1,2,4-thiadiazol-5-yl, 1,3,4-triazol-5-yl, 2-methyl-1,3,4-triazol-5-yl, 2- hydroxy-1,3,4-triazol-5-yl, 2-carboxy-4-methyl-1,3,4-triazol-5-yl, 2-carboxy-4-methyl- 1,3,4-triazol-5-yl, 1,3-oxazol-2-yl, 1,3,4-oxadiazol-5-yl, 2-methyl-1,3,4-oxadiazol-5-yl, 2- (hydroxymethyl)-1,3,4-oxadiazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-thiadiazol-5-yl, 2-thiol- 1,3,4-thiadiazol-5-yl, 2-(methylthio)-1,3,4-thiadiazol-5-yl,2-amino-1,3,4-thiadiazol-5- yl,1H-tetrazol-5-yl,1-methyl-1H-tetrazol-5-yl, 1-(1-(dimethylamino)eth-2-yl)-1H-tetrazol- 5-yl, 1-(carboxymethyl)-1H-tetrazol-5-yl, 1-(carboxymethyl)-1H-tetrazol-5-yl, 1- (methylsulfonic acid)-1H-tetrazol-5-yl, 1-(methylsulfonic acid)-1H-tetrazol-5-yl, 2-methyl- 1H-tetrazol-5-yl, 1,2,3-triazol-5-yl, 1-methyl-1,2,3-triazol-5-yl, 2-methyl-1,2,3-triazol-5-yl, 4-methyl-1,2,3-triazol-5-yl, pyrid-2-yl N-oxide, 6-methoxy-2-(n-oxide)-pyridaz-3-yl, 6- hydroxypyridaz-3-yl, 1-methylpyrid-2-yl, 1-methylpyrid-4-yl, 2-hydroxypyrimid-4-yl, 1,4,5,6-tetrahydro-5,6-dioxo-4-methyl-as-triazin-3-yl, 1,4,5,6-tetrahydro-4- (formylmethyl)-5,6-dioxo-as-triazin-3-yl, 2,5-dihydro-5-oxo-6-hydroxy-astriazin-3-yl, 2,5- dihydro-5-oxo-6-hydroxy-as-triazin-3-yl, 2,5-dihydro-5-oxo-6-hydroxy-2-methyl-astriazin- 3-yl, 2,5-dihydro-5-oxo-6-hydroxy-2-methyl-as-triazin-3-yl, 2,5-dihydro-5-oxo-6-methoxy- 2-methyl-as-triazin-3-yl, 2,5-dihydro-5-oxo-as-triazin-3-yl, 2,5-dihydro-5-oxo-2-methyl- as-triazin-3-yl, 2,5-dihydro-5-oxo-2,6-dimethyl-as-triazin-3-yl, tetrazolo[1,5-b]pyridazin-6- yl and 8-aminotetrazolo[1,5-b]-pyridazin-6-yl. An alternative group of “heteroaryl” includes; 4-(carboxymethyl)-5-methyl-1,3-thiazol-2-yl, 4-(carboxymethyl)-5-methyl-1,3- thiazol-2-yl, 1,3,4-triazol-5-yl, 2-methyl-1,3,4-triazol-5-yl, 1H-tetrazol-5-yl, 1-methyl-1H- tetrazol-5-yl, 1-(1-(dimethylamino)eth-2-yl)-1H-tetrazol-5-yl, 1-(carboxymethyl)-1H-tetrazol-5-yl, 1-(carboxymethyl)-1H-tetrazol-5-yl, 1-(methylsulfonic acid)-1H-tetrazol-5-yl, 1-(methylsulfonic acid)-1H-tetrazol-5-yl, 1,2,3-triazol-5-yl, 1,4,5,6-tetrahydro-5,6-dioxo- 4-methyl-as-triazin-3-yl, 1,4,5,6-tetrahydro-4-(2-formylmethyl)-5,6-dioxo-as-triazin-3-yl, 2,5-dihydro-5-oxo-6-hydroxy-2-methyl-as-triazin-3-yl, 2,5-dihydro-5-oxo-6-hydroxy-2- methyl-as-triazin-3-yl, tetrazolo[1,5-b]pyridazin-6-yl, and 8-aminotetrazolo[1,5- b]pyridazin-6-yl. Unless specified otherwise, the heteroaryl group may be substituted at one or more ring positions as described for heterocycles. The terms "heteroaryl" and "aryl" are mutually exclusive. "Heteroarylene" denotes a divalent heteroaryl radical.

[0084] The term "heteroatom" denotes an atom other than carbon and hydrogen. Typically, but not exclusively, heteroatoms are selected from the group consisting of halogen, sulfur, phosphorous, nitrogen, boron and oxygen atoms. Groups containing more than one heteroatom may contain different heteroatoms.

[0085] The terms “heterocyclic group”, “heterocyclic”, “heterocycle”, “heterocyclyl”, and “heterocyclo” as used herein, alone or as part of another group, are used interchangeably and refer to any mono-, bi-, or tricyclic, saturated or unsaturated, aromatic (heteroaryl) or non-aromatic ring having the number of atoms designated, generally from 5 to about 16 ring atoms, where the ring atoms are carbon and at least one heteroatom (nitrogen, sulfur or oxygen), for example, 1 to 4 heteroatoms. Heterocyclic groups include four to seven membered cyclic groups containing one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. Typically, a 5-membered ring has 0 to 2 double bonds and 6- or 7-membered ring has 0 to 3 double bonds. The nitrogen or sulfur heteroatoms may optionally be oxidized (e.g., SO, SO2), and any nitrogen heteroatom may optionally be quaternized. Particular non- aromatic heterocycles are morpholinyl (morpholino), pyrrolidinyl, oxiranyl, oxetanyl, tetrahydrofuranyl, 2,3-dihydrofuranyl, 2H-pyranyl, tetrahydropyranyl, thiiranyl, thietanyl, tetrahydrothietanyl, aziridinyl, azetidinyl, 1-methyl-2-pyrrolyl, piperazinyl and piperidinyl. Particular 5-membered heterocycles containing a sulfur or oxygen atom and one to three nitrogen atoms are thiazolyl, in particular thiazol-2-yl and thiazol-2-yl N-oxide, thiadiazolyl, in particular 1,3,4-thiadiazol-5-yl and 1,2,4-thiadiazol-5-yl, oxazolyl, for example oxazol-2-yl, and oxadiazolyl, such as 1,3,4-oxadiazol-5-yl, and 1,2,4-oxadiazol- 5-yl. Particular 5-membered ring heterocycles containing 2 to 4 nitrogen atoms include imidazolyl, such as imidazol-2-yl; triazolyl, such as 1,3,4-triazol-5-yl; 1,2,3-triazol-5-yl,1,2,4-triazol-5-yl, and tetrazolyl, such as 1H-tetrazol-5-yl. Particular benzo-fused 5- membered heterocycles are benzoxazol-2-yl, benzthiazol-2-yl and benzimidazol-2-yl. Particular 6-membered heterocycles contain one to three nitrogen atoms and optionally a sulfur or oxygen atom, for example pyridyl, such as pyrid-2-yl, pyrid-3-yl, and pyrid-4- yl; pyrimidyl, such as pyrimid-2-yl and pyrimid-4-yl; triazinyl, such as 1,3,4-triazin-2-yl and 1,3,5-triazin-4-yl; pyridazinyl, in particular pyridazin-3-yl, and pyrazinyl. The pyridine N-oxides and pyridazine N-oxides and the pyridyl, pyrimid-2-yl, pyrimid-4-yl, pyridazinyl and the 1,3,4-triazin-2-yl groups, are a particular group. Unless specified otherwise, the heterocyclo group may be substituted at one or more ring positions with hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkoxy, acyl, acyloxy, amino, aryloxy, carboxy, cyano, halogen, mercapto, oxo, nitro, thiol, sulfo, and the salts thereof.

[0086] The term “heterocyclocarbonyl” as used herein, alone or as part of another group, denotes a -C(O)R radical where R is heterocyclo as defined herein.

[0087] The terms "hydrocarbon group" and "hydrocarbyl group" as used herein, alone or as part of another group, are used interchangeably and denote organic radicals consisting exclusively of the elements carbon and hydrogen. These moieties include alkyl, alkenyl, and aryl moieties. These moieties also include alkyl, alkenyl, and aryl moieties substituted with other aliphatic or cyclic hydrocarbon groups, such as alkaryl and alkenaryl. Unless otherwise indicated, these moieties preferably comprise a chain of 1 to 25 carbon atoms, 1 to 20 carbon atoms, typically 1 to 12 carbon atoms, more typically 1 to 10 carbon atoms, and most typically 1 to 8 carbon atoms. Hydrocarbon groups may have a linear or branched chain structure. Typical hydrocarbon groups have one or two branches, typically one branch. Typically, hydrocarbon groups are saturated. Unsaturated hydrocarbon groups will typically have one or more double bonds.

[0088] The term "keto," as used herein, alone or as part of another group, denotes a double bonded oxygen moiety (i.e., =O) attached to a carbon atom.

[0089] The term “nitro” as used herein, alone or as part of another group, denotes a group of the formula –NO2.

[0090] "Optional" or "optionally" means that the subsequently described circumstance may but need not occur, and that the description includes instances where the circumstance occurs and instances in which it does not. For example, “optionally substituted alkyl” means that the alkyl group may or may not be further substituted. By way of further example, "optionally substituted alkoxy” means that the alkyl portion of the alkoxy group may, but need not be present, and the description includes embodiments in which the alkyl portion of the alkoxy group is substituted with one or more hetero atoms such as nitrogen, oxygen, silicon, phosphorous, boron, sulfur, or a halogen atom or by a heterocyclo groups.

[0091] The term “phenolic” as used herein, alone or as part of another group, refers to an aromatic hydrocarbon group having one or more hydroxy groups as a substituent. Examples include phenol (C6H5OH) and polyphenols.

[0092] The term “polyphenol” as used herein, alone or as part of another group, refers to naturally and non-naturally occurring phenolics. Examples of polyphenols include flavonoids, tannic acid, and ellagitannins.

[0093] The terms “siloxy” and “siloxyl” as used herein, alone or as part of another group, are used interchangeably and denote an organosilicon structure with the Si-O-Si linkage.

[0094] The terms "substituted hydrocarbyl," "substituted alkyl," "substituted alkenyl," “substituted alkoxy,” "substituted aryl," "substituted heterocyclo," and "substituted heteroaryl" as used herein, alone or as part of another group, denote hydrocarbyl, alkyl, alkenyl, alkoxy, aryl, heterocyclo, or heteroaryl moieties which are substituted with at least one atom other than carbon and hydrogen, including moieties in which a carbon chain or carbocyclic atom is substituted with a hetero atom such as nitrogen, oxygen, silicon, phosphorous, boron, sulfur, or a halogen atom. These substituents include halogen, heterocyclo, alkoxy, alkenoxy, aryloxy, hydroxy, keto, acyl, acyloxy, nitro, amino, amido, cyano, thiol, sulfo, sulfonate, esters and ethers.

[0095] The terms “siloxyalkyl” and “siloxylalkyl” as used herein, alone or as part of another group, are used interchangeably and denote an alkyl group substituted by a siloxy radical (e.g., 2-methyl-3-[methyl-bis(trimethylsilyloxy)silyl]propyl).

[0096] The term “sulfo” as used herein, alone or as part of another group, denotes a moiety having the structural formula –SO3H.

[0097] The term “sulfomethyl” as used herein, alone or as part of another group, denotes a moiety having the structural formula –CH2SO3H.

[0098] The term “sulfonate” as used herein denotes a moiety having the structural formula –SO3-.

[0099] The term “thiol” as used herein, alone or as part of another group, denotes a group of the formula –SH.

[0100] The term "vinyl," as used herein, alone or as part of another group, denotes a moiety having the structural formula RxHyC=CH-*, wherein * denotes the point of attachment of the moiety to the remainder of the molecule, the point of attachment is a heteroatom or aryl, and X and Y are independently 0, 1 or 2, such that X+Y=2, and R is hydrocarbyl or substituted hydrocarbyl.

[0101] The term "vinyl camphor" as used herein, alone or as part of another group, denotes a moiety having the structural formula: wherein R24 is optionally substituted–CH2SO3H, and the asterisk, *, denotes the point of attachment to the remainder of the composition.

[0102] With regard to stereoisomers, it should be understood that a solid line designation for the bonds in the compositions corresponding to the structural formulae disclosed herein for attachment of a substituent group to a chiral carbon atom of the compound indicates that these groups may lie either below or above the plane of the page (i.e., all isomeric forms of the compounds disclosed herein are contemplated, including racemates, racemic mixtures, and individual enantiomers or diastereomers). Additional Assays

[0103] The folowing assays may also be useful for characterising compositions of the invention and / or components thereof.

[0104] Solubility of one or more analytes in a given solvent at a particular temperature (e.g., 25 °C) may be determined by mixing the analyte with solvent at a loading greater than the expected solubility limit at the desired temperature (e.g., 25 °C). After mixing, the mixture is allowed to stand for an extended period of time at the desired temperature (e.g., 25 °C). The bulk phase of the solvent is collected, and the concentration of the analyte(s) may be determined by a suitable analytical technique such as absorbance spectroscopy, chromatography, or gravimetry.

[0105] Measurement of UV and visible light absorbance can be accomplished by dissolving a sample compound or mixture of compounds in a suitable transparent solvent, e.g. water or isopropanol. The solvent should have little to no absorbance in the wavelength range of interest (e.g.280 to 700 nm) and be able to completely dissolve the analyte(s). A container which is also suitably transparent in the wavelength range of interest, e.g. a quartz cuvette, is used to hold the sample solution. First, using a UV / Vis absorbance spectrometer with sufficient resolution (e.g.1 or 5 nm), a blank measurement of the solvent in the container is recorded. Second, the solution of the analyte(s) is placed in the container and its blank-corrected absorbance spectrum is recorded. The concentration of the analytes may be adjusted with solvent to ensure the maximal absorbance is not more than about 1.5. Absorbance spectra are commonly measured at room temperature (e.g., 25 °C).

[0106] Flieger, J.; Flieger, W.; Baj, J.; Maciejewski, R. Antioxidants: Classification, Natural Sources, Activity / Capacity Measurements, and Usefulness for the Synthesis of Nanoparticles. Materials 2021, 14, 4135 reviews the types of antioxidants and provides an overview of many types of in vitro antioxidant assays.

[0107] Zeb, A.; Ullah, F. A Simple Spectrophotometric Method for the Determination of Thiobarbituric Acid Reactive Substances in Fried Fast Foods. Journal of Analytical Methods in Chemistry 2016, 9412767 provides specific method parameters for testing thiobarbituric acid reactive substances in vitro (i.e end products of lipid peroxidation).

[0108] Fahlman, B.M.; Krol, E.S. Inhibition of UVA and UVB Radiation-Induced Lipid Oxidation by Quercetin. J. Ag. Food Chem.2009, 57 (12), 5301 provides specific method parameters for measurement of UVA and UVB-induced lipid peroxidation in vitro.

[0109] Moysan, A.; Marquis, I.; Gaboriau, F.; Santus, R.; Dubertret, L.; Morlière, P.; Ultraviolet A – Induced Lipid Peroxidation and Antioxidant Defense Systems in Cultured Human Skin Fibroblasts, J. Inv. Derm.1993, 100(5), 692 provides specific method parameters for measurement of UVA induced lipid peroxidation in cultured skin cells.

[0110] Eruslanov E.; Kusmartsev S. Identification of ROS using oxidized DCFDA and flow-cytometry. Methods Mol Biol.2010, 594, 57 provides specific method information for measurement of ROS in cells by flow cytometry or fluorescence quantification.

[0111] Jung, K.; Richter, J.; Kabrodt, K.; Lücke, I.M.; Schellenberg, I.; Herrling, Th. The antioxidative power AP—A new quantitative time dependent (2D) parameter for the determination of the antioxidant capacity and reactivity of different plants, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2006, 63 (4), 846 describes the measurement of antioxidant capacity in vitro by electron spin resonance.

[0112] Herrling, Th.; Jung, K.; Fuchs, J. Measurements of UV-generated free radicals / reactive oxygen species (ROS) in skin, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2006, 63 (4), 840 describes measurement of ROS formation in skin using electron spin resonance (in vivo / ex vivo).

[0113] Joël P.; Mouna-Messaouda K.; Jean-Paul C.B.; Jean-Olivier D.; Smail M. Electrochemical Methodology for Evaluating Skin Oxidative Stress Status (SOSS). Diseases.2019, 7(2), 40 describes the measurement of ROS formation in skin using an electrochemical approach.

[0114] Hanson, K.M.; Clegg, R.M. Observation and Quantification of Ultraviolet- induced Reactive Oxygen Species in Ex Vivo Human Skin. Photochemistry and Photobiology, 2002, 76, 57 describes the measurement of ROS formation in skin by two-photo fluorescence spectroscopy.

[0115] Oh, J.H.; Joo, Y.H.; Karadeniz, F.; Ko, J.; Kong, C.S. Syringaresinol Inhibits UVA-Induced MMP-1 Expression by Suppression of MAPK / AP-1 Signaling in HaCaT Keratinocytes and Human Dermal Fibroblasts. Int J Mol Sci.2020, 21(11), 3981 describes the measurement of aging-related RNA and protein expression in UV irradiated cells.

[0116] Vioux-Chagnoleau, C.; Lejeune, F.; Sok, J.; Pierrard, C.; Marionnet, C.; Bernerd, F. Reconstructed human skin: From photodamage to sunscreen photoprotection and anti-aging molecules, Journal of Dermatological Science Supplement, 2006, 2 (1), S1 and Marionnet, C.; Grether-Beck, S.; Seité, S.; Marini, A.; Jaenicke, T.; Lejeune, F.; Bastien P.; Rougier, A.; Bernerd, F.; Krutmann, J. A broad- spectrum sunscreen prevents UVA radiation-induced gene expression in reconstructed skin in vitro and in human skin in vivo. Exp Dermatol.2011, 20(6), 477 describe the measurement of aging-related RNA and protein expression in UV irradiated reconstructed skin and in vivo.

[0117] Armento, A.J.; Oldach, J.; Stolper, G.; Li, M.; Bachelor, M.A.; Hayden, P.J. Evaluation of Cutaneous Damage and Repair Following Acute Solar Ultraviolet Radiation Exposure: Experiments with an In Vitro Reconstructed Human Skin Model and Excised Human Skin. Applied In Vitro Toxicology, 2015, 109 describes the measurement of UV photodamage markers (histology, RNA and protein expression, and DNA damage) in reconstructed skin and ex vivo skin.

[0118] Brugè, F.; Tiano, L.; Astolfi, P.; Emanuelli, M.; Damiani, E. Prevention of UVA-Induced Oxidative Damage in Human Dermal Fibroblasts by New UV Filters, Assessed Using a Novel In Vitro Experimental System.2014, PLOS ONE 9(1), e83401 describes the measurement of UV photodamage markers in fibroblast cells following UVA exposure with or without a sunscreen barrier layer. UVA Absorption

[0119] The compositions of the invention may help to reduce damage to the skin caused by UVA radiation (e.g., photo-aging), e.g., by effectively absorbing high proportions of incident UVA radiation. Accordingly, in some embodiments the compositions of the invention will have a %UVA-T of no more than 90%, particularly nomore than 80%, particularly no more than 70%, particularly no more than 60%, particularly no more than 50%, particularly no more than 40%, particularly no more than 30%, particularly no more than 25%, particularly no more than 20%, particularly no more than 15%, particularly no more than 14%, particularly no more than 13%, particularly no more than 12%, particularly no more than 11%, particularly no more than 10%, particularly no more than 9%, particularly no more than 8%, particularly no more than 7%, particularly no more than 6%, particularly no more than 5%, particularly no more than 4%, particularly no more than 3%, particularly no more than 2%, particularly no more than 1%. For example, the compositions of the invention may have a %UVA-T of no more than 10%.

[0120] In particular embodiments, the method of measurement of %UVA-T is hybrid diffuse reflectance spectroscopy (HDRS). Accordingly, particular compositions of the invention have a %UVA-T of no more than 90%, particularly no more than 80%, particularly no more than 70%, particularly no more than 60%, particularly no more than 50%, particularly no more than 40%, particularly no more than 30%, particularly no more than 25%, particularly no more than 20%, particularly no more than 15%, particularly no more than 14%, particularly no more than 13%, particularly no more than 12%, particularly no more than 11%, particularly no more than 10%, particularly no more than 9%, particularly no more than 8%, particularly no more than 7%, particularly no more than 6%, particularly no more than 5%, particularly no more than 4%, particularly no more than 3%, particularly no more than 2%, particularly no more than 1%, as measured by hybrid diffuse reflectance spectroscopy. For example, compositions of the invention may have a %UVA-T of no more than 10%, as measured by hybrid diffuse reflectance spectroscopy (HDRS).

[0121] Alternatively, or in addition, to having a particular %UVA-T, in some embodiments the compositions of the invention will have a particular UVA-PF (e.g., as measured by monochromatic hybrid diffuse reflectance spectroscopy).

[0122] For instance, in some embodiments compositions of the invention may have a UVA-PF of at least 5, particularly at least 10, particularly at least 15, particularly at least 20, particularly at least 25, particularly at least 30, particularly at least 35, particularly at least 40, particularly at least 45, particularly at least 50, particularly at least 55, particularly at least 60, particularly at least 65, particularly at least 70,particularly at least 75, particularly at least 80, particularly at least 85, particularly at least 90, particularly at least 95, particularly at least 100. For example, the compositions of the invention may have a UVA-PF of at least 60.

[0123] UVA-PF may be measured by a series of different methods, e.g., in vivo UVA-PF, in vitro UVA-PF, or hybrid UVA-PF. In some embodiments, at least one of in vivo UVA-PF, in vitro UVA-PF, or hybrid UVA-PF of the composition is at least 5, particularly at least 10, particularly at least 15, particularly at least 20, particularly at least 25, particularly at least 30, particularly at least 35, particularly at least 40, particularly at least 45, particularly at least 50, particularly at least 55, particularly at least 60, particularly at least 65, particularly at least 70, particularly at least 75, particularly at least 80, particularly at least 85, particularly at least 90, particularly at least 95, particularly at least 100. For example at least one of in vivo UVA-PF, in vitro UVA-PF, or hybrid UVA-PF of the composition may be at least 60.

[0124] In particular embodiments, the method of measurement of UVA-PF is monochromatic hybrid diffuse reflectance spectroscopy (HDRS). Accordingly, particular compositions of the invention have a UVA-PF of at least 5, particularly at least 10, particularly at least 15, particularly at least 20, particularly at least 25, particularly at least 30, particularly at least 35, particularly at least 40, particularly at least 45, particularly at least 50, particularly at least 55, particularly at least 60, particularly at least 65, particularly at least 70, particularly at least 75, particularly at least 80, particularly at least 85, particularly at least 90, particularly at least 95, particularly at least 100, as measured by hybrid diffuse reflectance spectroscopy. For example, compositions of the invention may have a UVA-PF of at least 60, as measured by hybrid diffuse reflectance spectroscopy (HDRS). Limited Sunscreen Agents

[0125] In certain embodiments, the compositions of the invention contain a limited number or amount of organic UV filters. Usefully, this allows certain organic UV filters, which may undesirably be systemically absorbed through the skin of the user, to be reduced and / or omitted from compositions of the invention whilst retaining beneficial protection against skin photo-aging.

[0126] In some embodiments, compositions of the invention comprise no more than two different organic UV filters selected from 1-(4-Methoxyphenyl)-3-(4-tert- butylphenyl)-1,3-propanedione, tris-biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl- N,N-dimethylammonium)-2-hydroxypropane-1-sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3- phenylprop-2-enoate, 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate, hexyl 2-[4- (diethylamino)-2-hydroxybenzoyl]benzoate, 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino)benzoate, 2-phenyl-3H-benzimidazole-5-sulfonic acid, 2-ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4-methoxyphenyl)(2- hydroxyphenyl)methanone, (2-hydroxy-4-methoxyphenyl)(phenyl)methanone, 3,3,5- trimethylcyclohexyl 2-hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2-ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2- hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2-hydroxy- N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4-[(Z)-[7,7- Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3-benzotriazol- 2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4-methoxyphenyl)-1,3,5-triazine-2,4- diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3- benzimidazole-4-sulfonate), 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3- tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2- ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine-2,4- diyl)bis(azanediyl)]dibenzoate, 3-(3,4,5-trimethoxybenzylidene)-2,4-pentanedione, diethylhexylsyringylidene malonate, diethylhexyl-2,6-naphthalate, butyloctyl salicylate, tridecyl salicylate, benzotriazolyl dodecyl p-cresol, bis(cyano butylacetate) anthracenediylidene, phenoxyethyl caprylate, tris(PPG-3 benzyl ether) citrate and / or 3- Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, or a salt of any of the aforementioned. In particular embodiments, the compositions of the invention comprise no more than one of said organic UV filters.

[0127] In some embodiments, the concentration of organic UV filters is limited. For instance, in particular embodiments none of 1-(4-Methoxyphenyl)-3-(4-tert- butylphenyl)-1,3-propanedione, tris-biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl- N,N-dimethylammonium)-2-hydroxypropane-1-sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3- phenylprop-2-enoate, 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate, hexyl 2-[4- (diethylamino)-2-hydroxybenzoyl]benzoate, 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino)benzoate, 2-phenyl-3H-benzimidazole-5-sulfonic acid, 2-ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4-methoxyphenyl)(2- hydroxyphenyl)methanone, (2-hydroxy-4-methoxyphenyl)(phenyl)methanone, 3,3,5- trimethylcyclohexyl 2-hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2-ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2- hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2-hydroxy- N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4-[(Z)-[7,7- Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3-benzotriazol- 2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4-methoxyphenyl)-1,3,5-triazine-2,4- diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3- benzimidazole-4-sulfonate), 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3- tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2- ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine-2,4- diyl)bis(azanediyl)]dibenzoate, 3-(3,4,5-trimethoxybenzylidene)-2,4-pentanedione, diethylhexylsyringylidene malonate, diethylhexyl-2,6-naphthalate, butyloctyl salicylate, tridecyl salicylate, benzotriazolyl dodecyl p-cresol, bis(cyano butylacetate) anthracenediylidene, phenoxyethyl caprylate, tris(PPG-3 benzyl ether) citrate and / or 3- Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, nor any salt of any of the aforementioned, is present at a concentration of 1% or more by weight of a composition of the invention; more particularly, a concentration of 0.9% or more by weight of a composition of the invention; more particularly, a concentration of 0.8% or more byweight of a composition of the invention; more particularly, a concentration of 0.7% or more by weight of a composition of the invention; more particularly, a concentration of 0.6% or more by weight of a composition of the invention; more particularly, a concentration of 0.5% or more by weight of a composition of the invention. Absence of Sunscreen Agents

[0128] In certain embodiments, the compositions of the invention are not sunscreens. Usefully, this allows certain organic UV filters, which may be systemically absorbed through the skin of the user, to be omitted from compositions of the invention whilst retaining beneficial protection against skin photo-aging.

[0129] Accordingly, in certain embodiments, compositions of the invention may have an SPF of less than 20; particularly, compositions of the invention may have an SPF of less than 15; particularly, compositions of the invention may have an SPF of less than 10; particularly, compositions of the invention may have an SPF of less than 9; particularly, compositions of the invention may have an SPF of less than 8; particularly, compositions of the invention may have an SPF of less than 7; particularly, compositions of the invention may have an SPF of less than 6; particularly, compositions of the invention may have an SPF of less than 5; particularly, compositions of the invention may have an SPF of less than 4; particularly, compositions of the invention may have an SPF of less than 3; particularly, compositions of the invention may have an SPF of less than 2. For example, compositions of the invention may have an SPF of less than 10.

[0130] For example, in particular embodiments the compositions of the invention may contain substantially no 1-(4-Methoxyphenyl)-3-(4-tert-butylphenyl)-1,3- propanedione, tris-biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl-N,N- dimethylammonium)-2-hydroxypropane-1-sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3- phenylprop-2-enoate, 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate, hexyl 2-[4- (diethylamino)-2-hydroxybenzoyl]benzoate, 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino)benzoate, 2-phenyl-3H-benzimidazole-5-sulfonic acid, 2-ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4-methoxyphenyl)(2-hydroxyphenyl)methanone, (2-hydroxy-4-methoxyphenyl)(phenyl)methanone, 3,3,5- trimethylcyclohexyl 2-hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2-ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2- hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2-hydroxy- N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4-[(Z)-[7,7- Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3-benzotriazol- 2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4-methoxyphenyl)-1,3,5-triazine-2,4- diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3- benzimidazole-4-sulfonate), 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3- tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2- ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine-2,4- diyl)bis(azanediyl)]dibenzoate, and / or 3-Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2- enoate, 3-(3,4,5-trimethoxybenzylidene)-2,4-pentanedione, diethylhexylsyringylidene malonate, diethylhexyl-2,6-naphthalate, butyloctyl salicylate, tridecyl salicylate, benzotriazolyl dodecyl p-cresol, bis(cyano butylacetate) anthracenediylidene, phenoxyethyl caprylate, tris(PPG-3 benzyl ether) citrate or a salt of any of the aforementioned.

[0131] More particularly, compositions of the invention may contain substantially no 1-(4-Methoxyphenyl)-3-(4-tert-butylphenyl)-1,3-propanedione, tris-biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl-N,N-dimethylammonium)-2-hydroxypropane-1- sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl-2- cyano-3-(4-methoxyphenyl)-3-phenylprop-2-enoate, 2-ethylhexyl 2-cyano-3,3- diphenylprop-2-enoate, hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate, 4- aminobenzoic acid, 2-ethylhexyl 4-(dimethylamino)benzoate, 2-phenyl-3H- benzimidazole-5-sulfonic acid, 2-ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4-methoxyphenyl)(2-hydroxyphenyl)methanone, (2-hydroxy-4- methoxyphenyl)(phenyl)methanone, 3,3,5-trimethylcyclohexyl 2-hydroxybenzoate,(1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2-ethylhexyl (2E)-3-(4- methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2-hydroxybenzoate, 5-benzoyl-4-hydroxy-2- methoxybenzene-1-sulfonic acid, 2-hydroxy-N,N-bis(2-hydroxyethyl)ethan-1-aminium 2- hydroxybenzoate, [(3Z)-3-[[4-[(Z)-[7,7-Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3-benzotriazol- 2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4-methoxyphenyl)-1,3,5-triazine-2,4- diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3- benzimidazole-4-sulfonate), 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3- tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2- ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine-2,4- diyl)bis(azanediyl)]dibenzoate, and 3-Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2- enoate, or a salt of any of the aforementioned.

[0132] In other embodiments, compositions of the invention may contain substantially no 1-(4-Methoxyphenyl)-3-(4-tert-butylphenyl)-1,3-propanedione, 2-(2H- benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1- disiloxanyl]propyl]phenol, 2,2′-[6-(4-methoxyphenyl)-1,3,5-triazine-2,4-diyl]bis{5-[(2- ethylhexyl)oxy]phenol}, 2,2′-methylenebis[6-(2H-1,2,3-benzotriazol-2-yl)-4-(2,4,4- trimethylpentan-2-yl)phenol], 2-ethylhexyl 2-hydroxybenzoate, 4-[[4,6-bis[[4-(2- ethylhexoxy-oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate or a salt of any of the aforementioned.

[0133] In other more particular embodiments, compositions of the invention may contain substantially no [(3Z)-3-[[4-[(Z)-[7,7-Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, 1-(4-Methoxyphenyl)-3-(4-tert-butylphenyl)- 1,3-propanedione, 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3-tetramethyl- 1-[(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2′-[6-(4-methoxyphenyl)-1,3,5- triazine-2,4-diyl]bis{5-[(2-ethylhexyl)oxy]phenol}2,2′-methylenebis[6-(2H-1,2,3-benzotriazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], (RS)-2-Ethylhexyl (2E)-3-(4- methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate, 2- ethylhexyl 2-hydroxybenzoate, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3- phenylprop-2-enoate, 3-(3,4,5-trimethoxybenzylidene)-2,4-pentanedione, 3,3,5- trimethylcyclohexyl 2-hydroxybenzoate, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, benzotriazolyl dodecyl p-cresol, bis(2-ethylhexyl) 4,4′-[(6-{[4-(tert- butylcarbamoyl)phenyl]amino}-1,3,5-triazine-2,4-diyl)bis(azanediyl)]dibenzoate, bis(cyano butylacetate) anthracenediylidene, butyloctyl salicylate, diethylhexyl-2,6- naphthalate, diethylhexylsyringylidene malonate, disodium 2,2′-(1,4-phenylene)bis(6- sulfo-1H-1,3-benzimidazole-4-sulfonate), hexyl 2-[4-(diethylamino)-2- hydroxybenzoyl]benzoate, phenylene bis-diphenyltriazine, tris-biphenyl triazine or a salt of any of the aforementioned.

[0134] Alternatively, or in addition, the protection from UVB radiation offered by compositions of the invention may be limited. Accordingly, in some embodiments the compositions of the invention will have an SPF of at most 100, particularly at most 95, particularly at most 90, particularly at most 85, particularly at most 80, particularly at most 75, particularly at most 70, particularly at most 65, particularly at most 60, particularly at most 55, particularly at most 50, particularly at most 45, particularly at most 40, particularly at most 35, particularly at most 30, particularly at most 25, particularly at most 20, particularly at most 15, particularly at most 10, particularly at most 5. For example, the compositions of the invention may have an SPF of at most 15.

[0135] SPF may be measured by a series of different methods, e.g., in vivo SPF, in vitro SPF, or hybrid SPF. In some embodiments, at least one of in vivo SPF, in vitro SPF, or hybrid SPF of the composition is at most 100, particularly at most 95, particularly at most 90, particularly at most 85, particularly at most 80, particularly at most 75, particularly at most 70, particularly at most 65, particularly at most 60, particularly at most 55, particularly at most 50, particularly at most 45, particularly at most 40, particularly at most 35, particularly at most 30, particularly at most 25, particularly at most 20, particularly at most 15, particularly at most 10, particularly at most 5. For example, at least one of in vivo SPF, in vitro SPF, or hybrid SPF of the composition may be at most 15.

[0136] In particular embodiments, the method of measurement of SPF is an in vivo SPF measurement. Accordingly, some embodiments the compositions of the invention will have an SPF of at most 100, particularly at most 95, particularly at most 90, particularly at most 85, particularly at most 80, particularly at most 75, particularly at most 70, particularly at most 65, particularly at most 60, particularly at most 55, particularly at most 50, particularly at most 45, particularly at most 40, particularly at most 35, particularly at most 30, particularly at most 25, particularly at most 20, particularly at most 15, particularly at most 10, particularly at most 5, as measured by in vivo SPF. For example, the compositions of the invention may have an SPF of at most 15 as measured by in vivo SPF. UVA / UVB Absorption Ratio

[0137] The compositions of the invention may be particularly effective at providing protection from UVA without also absorbing excessive amounts of UVB radiation (e.g., without acting as a sunscreen). In particular embodiments, the compositions of the invention have a ratio of UVA-PF to SPF of at least 2:1 (e.g., 2:1, 3:1, 4:1, 5:1, 6:1, etc.). Particular compositions of the invention have a ratio of UVA-PF to SPF which is at least 2:1, particularly at least 3:1, particularly at least 4:1, particularly at least 5:1, particularly at least 6:1, particularly at least 7:1, particularly at least 8:1, particularly at least 9:1, particularly at least 10:1, particularly at least 15:1, particularly at least 20:1, particularly at least 30:1, particularly at least 40:1, particularly at least 50:1. For example, compositions of the invention might have a ratio of UVA-PF to SPF which is at least 5:1 (e.g., 5:1, 6:1, 7:1, etc.). Viscosity

[0138] Compositions of the invention may be adapted to have a desirable viscosity (e.g., by addition of thickeners). Viscosity can be measured by conventional methods which are known in the art. Typically a viscometer or rheometer is used to measure viscosities. Viscosities are typically expressed in centipoise (i.e., cP) which is equal to 1 millipascal second (i.e., 1 mPa∙s). Unless otherwise stated, viscosities are measured under standard conditions (e.g., 25 °C and 1 atm of pressure). For example,viscosity may be measured using a Brookfield DVIII Ultra, Spindle RV-5 at 10 r / min. Where a particular method is required, viscosity can be measured using a rheometer (e.g., a TA Instruments Discovery HR30) with 40mm parallel plate geometry and 600 micron gap on a peltier controlled stage at 25°C by conducting a flow sweep of shear rate from 10-3to 103sec-1. The viscosity at 1 / sec is reported, optionally in x1000 cPs (kcPs)

[0139] In some embodiments, the compositions of the invention have a viscosity of from 0.01 cP to 150,000 cP. For example, the compositions of the invention might have a viscosity of from 1,000 cP to 120,000 cP.

[0140] In particular embodiments, the compositions of the invention have a viscosity of from 0.01 cP to 100,000 cP. Particularly, compositions of the invention may have a viscosity of from 500 cP to 30,000 cP.

[0141] In other particular embodiments, compositions of the invention may have a viscosity of from 1,000 cP to 80,000 cP.

[0142] The inventors have also surprisingly discovered that UVA-PF of compositions of the invention can be improved by increasing viscosity of the compositions. Accordingly, particular compositions of the invention have a viscosity of at least 2,000 cP (i.e., 2 kcP); more particularly, at least 3 kcP; more particularly at least 10 kcP; more particularly, at least 15 kcP; more particularly, at least 18 kcP; more particularly, at least 50 kcP; more particularly, at least 75 kcP; more particularly, at least 80 kcP; more particularly, at least 85 kcP. Other Properties

[0143] In particular embodiments, the compositions of the invention are adapted to spread easily and homogenously on the skin surface during application. For example, compositions of the invention may be adapted to provide a transparent thin film on the surface of the skin. In particular embodiments compositions of the invention, feel lightweight and smooth. There are numerous inactive ingredients and formulation techniques that are known to experts in the field that can improve the application experience and resulting skin feel of compositions. For example, emollients, may be added to achieve good spreading and to make the skin feel smooth and soft.Humectants may be added to attract and retain moisture in the skin and improve the feel of the product. Thickeners may be added to manipulate product viscosity, spreading properties and feel on the skin. Various polymeric film-formers may be added to compositions of the invention to create a thin, breathable film on the skin. Texture modifiers may be added to improve product texture and to add non-greasy, slippery skin feel. The Antioxidant System

[0144] The compositions of the invention comprise an antioxidant system, wherein the antioxidant system comprises ROS agents.

[0145] An advantageous characteristic of the antioxidant system may be an ability to inhibit ROS generation. Accordingly, the antioxidant system may substantially inhibit ROS generation. For example, in certain embodiments the antioxidant system has an of ROS inhibition IC50 of 100mM or less; ; particularly, 10 mM or less; particularly, 5 mM or less; particularly, 1 mM or less; particularly, 500 µM or less; particularly, 400 µM or less; particularly, 300 µM or less; particularly, 200 µM or less; particularly, 100 µM or less; particularly, 50 µM or less; particularly, 40 µM or less; particularly, 30 µM or less; particularly, 20 µM or less; particularly, 10 µM or less; particularly, 1 µM or less. For example, the antioxidant system may have an ROS inhibition IC50 of 500 µM or less.

[0146] A further advantageous characteristic of the antioxidant system may be to provide ROS capture. Accordingly, in certain embodiments, the antioxidant system has an ROS capture IC50 which is suitable to provide effective ROS capture. In some embodiments, the antioxidant system has an ROS capture IC50 of no more than 10 mM; particularly, no more than 5 mM; particularly, no more than 4 mM; particularly, no more than 3 mM; particularly, no more than 2 mM; particularly, no more than 1 mM; particularly, no more than 500 µM; particularly, no more than 400 µM; particularly no more than 300 µM; particularly, no more than 200 µM; particularly, no more than 100 µM; particularly, no more than 50 µM; particularly, no more than 40 µM; particularly, no more than 30 µM; particularly, no more than 20 µM; particularly, no more than 10 µM; particularly, no more than 5 µM; particularly, no more than 4 µM; particularly, no morethan 3 µM; particularly, no more than 2 µM; particularly, no more than 1 µM. For example, the antioxidant system may have an ROS capture IC50 of no more than 200 µM.

[0147] An advantageous characteristic of the ROS agents (i.e., each ROS agent individually and / or the antioxidant system) may be an ability to inhibit ROS generation. Accordingly, the ROS agents (i.e., each ROS agent individually and / or the antioxidant system) may substantially inhibit ROS generation. For example, in certain embodiments the ROS agents (i.e., each ROS agent individually and / or the antioxidant system) have an of ROS inhibition IC50 of 100mM or less; ; particularly, 10 mM or less; particularly, 5 mM or less; particularly, 1 mM or less; particularly, 500 µM or less; particularly, 400 µM or less; particularly, 300 µM or less; particularly, 200 µM or less; particularly, 100 µM or less; particularly, 50 µM or less; particularly, 40 µM or less; particularly, 30 µM or less; particularly, 20 µM or less; particularly, 10 µM or less; particularly, 1 µM or less. For example, the ROS agents (i.e., each ROS agent individually and / or the antioxidant system) may have an ROS inhibition IC50 of 500 µM or less.

[0148] A further advantageous characteristic of the ROS agents may be to provide ROS capture. Accordingly, in certain embodiments, the ROS agents (i.e., each ROS agent individually and / or the antioxidant system) have an ROS capture IC50 which is suitable to provide effective ROS capture. In some embodiments, the ROS agents (i.e., each ROS agent individually and / or the antioxidant system) have an ROS capture IC50 of no more than 10 mM; particularly, no more than 5 mM; particularly, no more than 4 mM; particularly, no more than 3 mM; particularly, no more than 2 mM; particularly, no more than 1 mM; particularly, no more than 500 µM; particularly, no more than 400 µM; particularly no more than 300 µM; particularly, no more than 200 µM; particularly, no more than 100 µM; particularly, no more than 50 µM; particularly, no more than 40 µM; particularly, no more than 30 µM; particularly, no more than 20 µM; particularly, no more than 10 µM; particularly, no more than 5 µM; particularly, no more than 4 µM; particularly, no more than 3 µM; particularly, no more than 2 µM; particularly, no more than 1 µM. For example, the ROS agents (i.e., each ROS agent individually and / or the antioxidant system) may have an ROS capture IC50 of no more than 200 µM.

[0149] In some embodiments, the compositions of the invention comprise the antioxidant system, wherein the total amount of the antioxidant system in thecomposition is from about 1% to about 50%, particularly from about 10% to about 40%, particularly from about 15% to about 30%, (by weight) of the composition. For example, the total amount of the antioxidant system in the compositions of the invention might be from about 10% to about 40% (by weight) of the composition.

[0150] ROS agents may comprise polymeric ROS agents and / or free ROS agents as described herein. In particular embodiments, the antioxidant system comprises a polymeric ROS agent and a free ROS agent. The Polymeric ROS Agent

[0151] Compositions of the invention may comprise a polymeric ROS agent as part of the antioxidant system. For example, the ROS inhibitor may comprise a polymeric ROS agent.

[0152] Generally, an advantageous characteristic of the polymeric ROS agent may be an ability to absorb UVA radiation. Accordingly, the polymeric ROS agent may be any suitable polymer having an absorption peak in the UVA wavelength range. For example, in certain embodiments the polymeric ROS agent is any polymer having an absorption maximum of from 300 nm to 400 nm.

[0153] In various embodiments, the ROS inhibitor present in compositions of the invention may be a polymeric ROS agent having an absorption maximum for ultraviolet radiation in the wavelength range of from 250 nm to 400 nm; and an E11 of at least 50 for ultraviolet radiation in the wavelength range of from 250 nm to 400 nm.The polymeric ROS agent may be any polymer which is of a suitable molecular weight likely to have little to no permeation through the skin into systemic circulation. For example, in certain embodiments, the polymeric ROS agent is any polymer having a molecular weight of at least 100 Da; particularly, at least 200 Da; particularly, at least 300 Da; particularly, at least 400 Da; particularly, at least 500 Da; particularly, at least 600 Da; particularly, at least 700 Da; particularly, at least 800 Da; particularly, at least 900 Da; particularly, at least 1000 Da; particularly, at least 1100 Da; particularly, at least 1200 Da; particularly, at least 1300 Da; particularly, at least 1400 Da; particularly, at least 1500 Da; particularly, at least 1600 Da; particularly, at least 1700 Da; particularly, at least 1800 Da; particularly, at least 1900 Da; particularly, at least 2000 Da; particularly,at least 10000 Da; particularly, at least 20000 Da; particularly, at least 30000 Da; particularly, at least 40000 Da; particularly, at least 50000 Da. For example, the polymeric ROS agent may be any suitable polymer having a molecular weight of at least 500 Da. Advantageously, such polymeric ROS agents are unlikely to penetrate the stratum corneum, epidermis, and dermis, thus they are unlikely to be systemically absorbed. For instance, compounds with molecular weight greater than 500 Da, extreme hydrophilicity or hydrophobicity (i.e. LogPow < 1 or > 4), and those with few functional groups might be expected to have minimal to no skin penetration.

[0154] Generally, a further advantageous characteristic of the polymeric ROS agent may be an ability to inhibit ROS generation. Accordingly, the polymeric ROS agent may be any suitable polymer which substantially inhibits ROS generation. For example, in certain embodiments the polymeric ROS agent is any polymer having an of ROS inhibition IC50 of 100mM or less; particularly, 10 mM or less; particularly, 5 mM or less; particularly, 1 mM or less; particularly, 500 µM or less; particularly, 400 µM or less; particularly, 300 µM or less; particularly, 200 µM or less; particularly, 100 µM or less; particularly, 50 µM or less; particularly, 40 µM or less; particularly, 30 µM or less; particularly, 20 µM or less; particularly, 10 µM or less; particularly, 1 µM or less. For example, the polymeric ROS agent may be any polymer having an ROS inhibition IC50 of 500 µM or less.

[0155] In certain embodiments the polymeric ROS agent substantially inhibits ROS generation (e.g., as described above) and / or has an absorption maximum of from 300 nm to 400 nm; and has a suitable molecular weight. For example, the polymeric ROS agent may be any polymer having an ROS inhibition IC50 of 500 μM or less and / or an absorption maximum of from 300 nm to 400 nm; and a molecular weight of at least 500 Da.

[0156] In some embodiments, the compositions of the invention comprise the polymeric ROS agent, wherein the total amount of the polymeric ROS agent in the composition is from about 1% to about 50%, particularly from about 10% to about 40%, particularly from about 15% to about 30%, (by weight) of the composition. For example, the total amount of the polymeric ROS agent in the compositions of the invention might be from about 10% to about 40% (by weight) of the composition.

[0157] In particular embodiments, the polymeric ROS agent may comprise a polymer backbone comprising repeat units derived from monomers, wherein the number of repeat units in the backbone is a natural number (r), and wherein the polymer backbone is covalently attached to one or more variable groups (XA, XB, and / or X) which are radicals derived from molecular moieties. The variable groups and / or repeat units may be covalently bonded directly to the repeat units comprised by the polymer backbone or, alternatively, via a linker (L) as illustrated in Formula 1: X (Formula 1); wherein the terminalindependently absent, or independently selected from X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; X wherein the repeat unit, wherein each X is independently absenthydrocarbyl, substituted hydrocarbyl, or heterocyclyl; and L is the optional linker, which may be a linker moiety or a covalent bond.

[0158] Generally, for a polymer disclosed herein at least one of XA and XB is X1 and / or at least one instance of X in at least one repeat unit is X1.

[0159] In particular embodiments, at least one of XA and XB is X1.

[0160] In certain embodiments, at least one of XA and XB is X1; and no instance of X is X1.

[0161] In certain embodiments, one of XA or XB is X1. In particular embodiments, one of XA or XB is X1; and at least one instance of X in at least one repeat unit is X1. In other particular embodiments, one of XA or XB is X1; and no instance of X is X1.

[0162] In certain embodiments, both of XA and XB are X1. In particular embodiments, both of XA and XB are X1; and at least one instance of X in at least one repeat unit is X1. In other particular embodiments, both of XA and XB are X1; and no instance of X is X1.

[0163] Usefully, the polymer of Formula 1 may have the functional characteristics described herein in relation to the polymeric ROS agent. For instance, in some embodiments, the polymer of Formula 1 will have an ROS inhibition IC50 of 10 mM or less and / or an absorption maximum in the range of 250-400 nm; optionally 300-400 nm.

[0164] Usefully, X1 may have the functional characteristics described herein relation to the polymeric ROS agent. For instance, in some embodiments, X1 will have an ROS inhibition IC50 of 10 mM or less and / or an absorption maximum in the range of 250-400 nm; optionally 300-400 nm.

[0165] In general, the polymer may be a linear, branched, or dendrimer polymer that is optionally crosslinked. In certain embodiments, the polymer has a substantially or entirely linear structure.

[0166] Generally, the type of polymer which forms the polymer backbone is not particularly limited and can be chosen from the polymer types known to the skilled person. Examples of suitable polymer types include polyesters, polyethers, polyurethanes, polycarbonates, polysiloxanes, polyacrylates, polyalcohols, polyolefins, polyvinylpyrrolidones, polyoxazolines, polystyrenes, polysaccharides, polymaleic acids, polylactones, polyamides, naturally occuring polymers (e.g., chitosan), and copolymers of each of the foregoing.

[0167] In certain embodiments, the repeat unit of Formula 1 corresponds to one of Formulae 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 1I, 1J, 1K, 1L, 1M, 1N or a combination thereof:wherein: ^ L is a covalent bond or a linker covalently attaching X1 to the remainder of the structure,^ X1 is a as further described herein, ^ Each of X2 – X7 is hydrocarbyl or optionally substituted hydrocarbyl, and ^ Each of X8, X9 or X10 is X1, hydrogen, hydrocarbyl or substituted hydrocarbyl.

[0168] In general, L is absent (i.e., L is a covalent bond), or aliphatic, substituted aliphatic, alicyclic, acyloxy, acylakyl, alkoxy, or polyether. In particular embodiments, the linker may be an alkyl (e.g., C1-C10 alkyl), heteroalkyl, aryl, or heteroaryl; or alkyl (e.g., C1-C10 alkyl) ether, heteroalkyl ether, aryl ether, or heteroaryl ether; or alkyl (e.g., C1- C10 alkyl) ester or heteroalkyl ester; or alkyl (e.g., C1-C10 alkyl) amide or heteroalkyl amide; or alkyl (e.g., C1-C10 alkyl) sulfide, heteroalkyl sulfide, aryl sulfide, or heteroaryl sulfide. The connections between L and X1 and L and the polymer backbone can be made in many ways and include esters, amides, ethers, amines, aryl-alkyl, and carbon- silicone connections.

[0169] In general, X 1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties.

[0170] Polymers that can be derivatized with the desired properties include but are not limited to: polyacrylates, polysiloxanes, polyesters, polyalcohols, polyolefins, polyurethanes, polyvinylpyrrolidones, polyoxazolines, polystyrenes, polysacharrides, polymaleic acids, polylactones, polyamides, naturally occurring polymers such as chitosan, and copolymers thereof.

[0171] In one embodiment, X1 is selected from groups corresponding to Formula A2:whereinthe A ring is aryl, carbocyclic, or heterocyclic, R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, each R2 is independently is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, and n is 0-5.

[0172] For example, in one such embodiment in which X1corresponds to Formula A2, Ring A is cyclohexyl, phenyl, naphthyl, triazinyl, or anthracenediylidenyl. By way of further example, in one such embodiment, Ring A is cycloalkenyl, R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, each R2 is independently is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, and n is 1-5. By way of further example, in one such embodiment, Ring A is phenyl, R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, each R2 is independently is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, and n is 1-5. By way of further example, in one such embodiment, Ring A is naphthyl, R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, each R2 is independently is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, and n is 1-5. By way of further example, in one such embodiment, Ring A is polyphenol, R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, each R2 is independently is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, and n is 1-5. By way of further example, in one such embodiment, Ring A is a naturally occurring polyphenol, R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, each R2 is independently is hydrogen, optionally substituted alkyl, optionally substitutedalkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, and n is 1-5. By way of further example, in one such embodiment, Ring A is triazinyl, R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, each R2 is independently is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, and n is 1-5. By way of further example, in one such embodiment, Ring A is anthracenediylidenyl, R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, each R2 is independently is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, and n is 1-5.

[0173] In one embodiment , X1 corresponds to Formula 2: wherein R1 is hydrogen,substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, alkoxycarbonyl, aryl, arylalkyl, or heterocyclo, each R2 is independently is optionally substituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, amino, aryl, arylalkyl, or heterocyclo, and n is 0-5.

[0174] In one embodiment, X1 corresponds to Formula 2Awherein R2 and n are as defi mula 2 and R11 is optionally substituted alkyl, optionally substituted alkoxy, aralkenyl, aryl, hydroxyl, or heterocyclo. For example, in one such embodiment in which X1 corresponds to Formula 2A, R2 and n are as defined in connection with Formula 2 and R11 is acylalkyl, optionally substituted alkyl, optionally substituted alkoxy, aralkenyl, aryl, or hydroxyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2A, R2 and n are as defined in connection with Formula 2 and R11 is acylalkyl, aralkenyl, aryl, or hydroxyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2A, R11 is acylalkyl, aralkenyl, aryl, or hydroxyl, each R2 is independently selected from the group consisting of hydroxyl, amino, acyl, acyloxy, optionally substituted alkyl and optionally substituted alkoxy and n is 0-3.

[0175] In one embodiment, X1 corresponds to Formula 2A-1 O Owherein R2 and n are and R116 is optionally substituted alkyl, optionally substituted alkoxy, aralkenyl, aryl, hydroxyl, or heterocyclo. For example, in one such embodiment in which X1 corresponds to Formula 2A-1, R2 and n are as defined in connection with Formula 2 and R116 is optionally substituted alkyl, optionally substituted alkoxy, aryl, or hydroxyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2A-1, R2 and n are as defined in connection with Formula 2 and R116 is aryl. By way of further example, in one suchembodiment in which X1 corresponds to Formula 2A-1, R2 and n are as defined in connection with Formula 2 and R116 is optionally substituted phenyl wherein the phenyl substituents are selected from alkoxy and alkyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2A-1, R116 is optionally substituted phenyl wherein the phenyl substituents are selected from alkoxy and alkyl, each R2 is independently selected from the group consisting of hydroxyl, optionally substituted alkyl and optionally substituted alkoxy and n is 0-3.

[0176] In one embodiment, X1 corresponds to Formula 2B wherein R2 and n are as2 and R112 is optionally substituted alkyl, aryl, or hydrogen. For example, in one such embodiment in which X1 corresponds to Formula 2B, R2 and n are as defined in connection with Formula 2 and R112 is optionally substituted alkyl, aryl, or hydrogen. By way of further example, in one such embodiment in which X1corresponds to Formula 2A, R2and n are as defined in connection with Formula 2 and R112 is aryl or hydrogen. By way of further example, in one such embodiment in which X1 corresponds to Formula 2A, R112 is optionally substituted phenyl or hydrogen, each R2 is independently selected from the group consisting of hydroxyl, amino, acyl, acyloxy, optionally substituted alkyl and optionally substituted alkoxy, and n is 0-3.

[0177] In one embodiment, X1 corresponds to Formula 2Cwherein R2 and n are as defined in connection with Formula 2 and R13 is acylalkyl. For example, in one such embodiment in which X1 corresponds to Formula 2C, R2 and n are as defined in connection with Formula 2 and R13 is –CHC(O)R131 wherein R131 is optionally substituted alkyl, aryl or heterocyclo. By way of further example, in one such embodiment in which X1 corresponds to Formula 2C, R2 and n are as defined in connection with Formula 2 and R13 is –CHC(O)R131 wherein R131 is aryl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2C, R2 and n are as defined in connection with Formula 2 and R13 is –CHC(O)R131 wherein R131 is optionally substituted phenyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2C, R13 is -CHC(O)R131 wherein R131 is optionally substituted phenyl, each R2 is independently selected from the group consisting of hydroxyl, amino, acyl, acyloxy, optionally substituted alkyl and optionally substituted alkoxy, and n is 0-3. By way of further example, in one such embodiment in which X1 corresponds to Formula 2C, R13 is -CHC(O)R131 wherein R131 is substituted phenyl, each R2 and phenyl substituent is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3. By way of further example, in one such embodiment in which X1 corresponds to Formula 2C, R13 is -CHC(O)R131 wherein R131 is (unsubstituted) phenyl, each R2 is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3.

[0178] In one embodiment, X1 corresponds to Formula 2C-1wherein R2 and n are as defined in connection with Formula 2 and R120 and R121 are independently optionally substituted alkyl, aryl, heterocyclo or R120 and R121 and the nitrogen atom to which they are attached form a heterocycle. For example, in one such embodiment in which X1 corresponds to Formula 2C-1, R2 and n are as defined in connection with Formula 2 and R120 and R121 are independently optionally substituted alkyl. By way of further example, in one such embodiment in which X1 corresponds toFormula 2C-1, R120 and R121 are independently optionally substituted alkyl, each R2 is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3.

[0179] In one embodiment, X1 corresponds to Formula 2D wherein R2 and n are as2 and R12 is hydrogen or optionally substituted alkyl. For example, in one such embodiment in which X1 corresponds to Formula 2D, R2 and n are as defined in connection with Formula 2 and R12 is hydrogen or alkyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2D, R2 and n are as defined in connection with Formula 2 and R12 is branched alkyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2D, R12 is substituted alkyl, each R2 and alkyl substituent is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3. By way of further example, in one such embodiment in which X1 corresponds to Formula 2D, R12 is (unsubstituted) alkyl, each R2 is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3.

[0180] In one embodiment, X1 corresponds to Formula 2E Owherein R2 and n are as 2 and R14 is optionally substituted alkyl. For example, in one such embodiment in which X1 corresponds to Formula 2E, R2 and n are as defined in connection with Formula 2 and R14 is substituted alkyl. By way of further example, in one such embodiment in which X1corresponds to Formula 2E, R2 and n are as defined in connection with Formula 2 and R14 is branched alkyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2E, R14 is substituted alkyl, each R2 and alkyl substituent is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3. By way of further example, in one such embodiment in which X1 corresponds to Formula 2E, R14 is (unsubstituted) alkyl, each R2 is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3.

[0181] In one embodiment, X1 corresponds to Formula 2Fwherein R2 and n are as defined in connection with Formula 2 and R131 is hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, aralkenyl, aryl or heterocyclo. For example, in one such embodiment in which X1 corresponds to Formula 2F, R2 and n are as defined in connection with Formula 2 and R131 is optionally substituted alkyl, optionally substituted alkoxy, or aralkenyl, By way of further example, in one such embodiment in which X1 corresponds to Formula 2F, R2 and n are as defined in connection with Formula 2 and R131 is –CH2-aryl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2F, R2 and n are as defined in connection with Formula 2 and R131 is –CH2-aryl wherein the aryl group is phenyl and the phenyl moiety is hydroxyl and methoxy substituted. By way of further example, in one such embodiment in which X1 corresponds to Formula 2F, R131 is –CH2-aryl, the aryl group is phenyl, the phenyl moiety is hydroxyl and methoxy substituted, each R2 is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3.

[0182] In one embodiment, X1 corresponds to Formula 2F-1where droxyl, optionally substituted alkyl, optionally substituted alkoxy, hydroxyl, or amino, and m is 0- 3. For example, in one such embodiment in which X1 corresponds to Formula 2F-1, R2 and n are as defined in connection with Formula 2, each R1311 is optionally substituted alkyl, optionally substituted alkoxy, or hydroxyl, and m is 0-3, By way of further example, in one such embodiment in which X1 corresponds to Formula 2F-1, R2 and n are as defined in connection with Formula 2, each R1311is alkoxy or hydroxyl, and m is 1-2. By way of further example, in one such embodiment in which X1 corresponds to Formula 2F-1, R2 and n are as defined in connection with Formula 2, each R131 is methoxy or hydroxyl and m is 0-2. By way of further example, in one such embodiment in which X1 corresponds to Formula 2F-1, each R131 is alkoxy or hydroxyl, m is 1-2, each R2 is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 1-2.

[0183] In one embodiment, X1 corresponds to Formula 2G O mwherein R2 and n each R117 is independently hydroxyl, acyl, acyloxy, alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkoxy, or amino and m is 0-3. For example, in one such embodiment in which X1 corresponds to Formula 2G, R2 and n are as defined in connection with Formula 2, each R117 is independently acyloxy, alkoxycarbonyl,optionally substituted alkyl, or optionally substituted alkoxy, and m is 0-3, By way of further example, in one such embodiment in which X1 corresponds to Formula 2G, R2 and n are as defined in connection with Formula 2, R117 is –C(O)OR1171 wherein R1171 is alkyl, and m is 1. By way of further example, in one such embodiment in which X1 corresponds to Formula 2G, R2 and n are as defined in connection with Formula 2, each R117 is acyl, alkoxy, hydroxyl or amino and m is 1-2. By way of further example, in one such embodiment in which X1 corresponds to Formula 2G, each R117 is acyl, alkoxycarbonyl, hydroxyl or amino, m is 1-2, each R2 is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3.

[0184] In one embodiment, X1 corresponds to Formula 2H wherein R2 and nis acyl or alkoxycarbonyl, R114 is cyano or alkoxycarbonyl, and each R117 is independently hydroxyl, acyl, acyloxy, alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkoxy, or amino and m is 0-3. For example, in one such embodiment in which X1 corresponds to Formula 2H, R2 and n are as defined in connection with Formula 2, R113 is acyl or alkoxycarbonyl, R114 is cyano or alkoxycarbonyl, each R117 is independently acyloxy, alkoxycarbonyl, optionally substituted alkyl, or optionally substituted alkoxy, and m is 0-3, By way of further example, in one such embodiment in which X1 corresponds to Formula 2H, R2 and n are as defined in connection with Formula 2, R113 is acyl or alkoxycarbonyl, R114 is cyano or alkoxycarbonyl, and m is 0. By way of further example, in one such embodiment in which X1 corresponds to Formula 2H, R2 and n are as defined in connection with Formula 2, R113 is acyl or alkoxycarbonyl, R114 is cyano, and m is 0. By way of further example, in one such embodiment in which X1 corresponds to Formula 2H, R113 is alkoxycarbonyl, R114 iscyano, m is 0, each R2 is independently selected from the group consisting of hydroxyl, amino, alkyl and alkoxy, and n is 0-3.

[0185] In one embodiment, X1 corresponds to Formula 2H-1 wherein R2 and nis alkyl, each R117 is independently hydroxyl, acyl, acyloxy, alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkoxy, or amino and m is 0-3. For example, in one such embodiment in which X1 corresponds to Formula 2H-1, R2 and n are as defined in connection with Formula 2, R1141 is alkyl, each R117 is independently acyloxy, alkoxycarbonyl, optionally substituted alkyl, or optionally substituted alkoxy, and m is 0- 3, By way of further example, in one such embodiment in which X1 corresponds to Formula 2H-1, R2 and n are as defined in connection with Formula 2, R1141 is alkyl, and m is 0. By way of further example, in one such embodiment in which X1 corresponds to Formula 2H-1, R1141 is alkyl, R117 and R2 are independently alkyl or alkoxy, m is 0 or 1, and n is 0 or 1.

[0186] In one embodiment, X1 corresponds to Formula 2H-1wherein R2 and n are as R117 is independently hydroxyl, acyl, acyloxy, alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkoxy, amino, or heterocyclo and d is 0-3. For example, in onesuch embodiment in which X1 corresponds to Formula 2I, R2 and n are as defined in connection with Formula 2, each R117 is independently optionally substituted alkyl, optionally substituted alkoxy, hydroxyl and heterocyclo, and d is 1-3, By way of further example, in one such embodiment in which X1 corresponds to Formula 2I, R2 and n are as defined in connection with Formula 2, each R117 is independently optionally substituted alkyl, optionally substituted alkoxy, hydroxyl and heterocyclo and d is 3. By way of further example, in one such embodiment in which X1 corresponds to Formula 2I, each R117 is independently optionally substituted alkyl, optionally substituted alkoxy, hydroxyl and heterocyclo, m is 3, each R2 is independently optionally substituted alkyl, optionally substituted alkoxy, hydroxyl and heterocyclo, and n is 3. In each of the foregoing exemplary embodiments recited in connection with Formula 2I, heterocyclo includes optionally substituted benzotriazole and optionally substituted benzimidazole.

[0187] In one embodiment, X1 corresponds to Formula 2K R24R1wherein R1is asoptionally substituted alkyl, and t is 1 or 2. For example, in one such embodiment in which X1 corresponds to Formula 2K, R1 is as defined in connection with Formula 2, R24 is alkyl or sulfo or sulfonate substituted alkyl, and t is 1 or 2. By way of further example, in one such embodiment in which X1 corresponds to Formula 2K, R1 is hydrogen, R24 is alkyl or sulfo or sulfonate substituted alkyl, and t is 1 or 2. By way of further example, in one such embodiment in which X1 corresponds to Formula 2K, R1 is hydrogen, R24 is alkyl or sulfo or sulfonate substituted alkyl, and t is 1. By way of further example, in one such embodiment in which X1 corresponds to Formula 2K, R1 is hydrogen, R24 is alkyl or sulfo or sulfonate substituted alkyl, and t is 2.

[0188] In one embodiment, X1 corresponds to Formula 2Mwherein R1 is as defined in connection with Formula 2, each R3 is independently hydroxyl, alkoxy, or optionally substituted alkyl, u is 0-3, t is 1-2, A is carbon or nitrogen, R25 is sulfo or sulfate, and z is 0 or 1. For example, in one such embodiment in which X1 corresponds to Formula 2M, R1 is optionally substituted alkyl, each R3 is independently hydroxyl, alkoxy, or optionally substituted alkyl, u is 0-3, t is 1-2, A is carbon or nitrogen, R25 is sulfo or sulfate, and z is 0 or 1. By way of further example, in one such embodiment in which X1 corresponds to Formula 2M, in one such embodiment in which X1 corresponds to Formula 2M, R1 is alkyl, each R3 is independently hydroxyl, alkoxy, or siloxylalkyl, u is 1-3, t is 1-2, A is carbon or nitrogen, R25is sulfo or sulfate, and z is 0 or 1. By way of further example, in one such embodiment in which X1 corresponds to Formula 2M, in one such embodiment in which X1 corresponds to Formula 2M, R1 is alkyl, each R3 is independently hydroxyl, alkoxy, or siloxylalkyl, u is 1-3, t is 1, A is nitrogen, R25 is sulfo or sulfate, and z is 0.

[0189] In one embodiment, X1 corresponds to Formula 2Nwherein R2 and n are as defined in connection with Formula 2, R113 and R114 are independently acyl, alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkoxy, amino, or heterocyclo. For example, in one such embodiment in which X1corresponds to Formula 2N, R2 and n are as defined in connection with Formula 2, R113 and R114 are independently acyl, alkoxycarbonyl, or optionally substituted alkyl. By wayof further example, in one such embodiment in which X1 corresponds to Formula 2N, R113 and R114 are each –C(O)R1131 wherein each R1131 is independently alkyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2N, R113 and R114 are each –C(O)R1131 wherein each R1131 is methyl. In each of the foregoing exemplary embodiments recited in connection with Formula 2N, each R2 is independently optionally substituted alkyl, optionally substituted alkoxy, or hydroxyl, and n is 3.

[0190] In one embodiment, X1 corresponds to Formula 2Owherein R2 and n are as defined in connection with Formula 2, R1 is acyl, alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkoxy, or amino. For example, in one such embodiment in which X1 corresponds to Formula 2O, R2 and n are as defined in connection with Formula 2, R1 is acyl, alkoxycarbonyl, alkoxy or optionally substituted alkyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2O, R1 is acyl or alkoxycarbonyl. By way of further example, in one such embodiment in which X1 corresponds to Formula 2O, R1 is alkoxycarbonyl. In each of the foregoing exemplary embodiments recited in connection with Formula 2O, each R2 is independently optionally substituted alkyl, optionally substituted alkoxy, acyl, alkoxycarbonyl or hydroxyl, and n is 1-3.

[0191] In one embodiment, X1 corresponds to Formula 2O-1

[0192] wherein R27 and R28 are optionally substituted alkyl.

[0193] In one embodiment, X1 corresponds to Formula 3wherein M1, M2, and M3are independently amino or aryl. For example, in one such embodiment M1, M2, and M3are independently amino. By way of further example, in one such embodiment M1, M2, and M3are -NHM11, -NHM22and –NHM33, respectively wherein M11, M22, and M33are independently aryl. By way of further example, in one such embodiment M1, M2, and M3are -NHM11, -NHM22and –NHM33, respectively wherein M11, M22, and M33are –C6H4M99wherein M99is alkoxycarbonyl or amido. By way of further example, in one such embodiment M1, M2, and M3are -NHM11, -NHM22and –NHM33, respectively wherein M11, M22, and M33are –C6H4M99wherein M99is phenyl.

[0194] In one embodiment, X1 corresponds to Formula 3Awherein M11, M22, and M33are independently acyl, alkoxy, alkoxycarbonyl or aryl and e, f and g are independently 0-2. For example, in one such embodiment M11, M22, and M33are independently alkoxy. By way of further example, in one such embodiment M11, M22, and M33are independently aryl, e.g., optionally substituted phenyl. By way of further example, in one such embodiment M11, M22, and M33are independently alkoxycarbonyl.

[0195] In one embodiment, X1 corresponds to Formula 3Bwherein M111, M222, and M333are independently alkoxy, alkoxycarbonyl or aryl and h, i and j are independently 0-2. For example, in one such embodiment M111, M222, and M333are independently acyl, alkoxy, alkoxycarbonyl or aryl. By way of further example, in one such embodiment M111, M222, and M333are independently alkoxycarbonyl. By way of further example, in one such embodiment M111, M222, and M333are independently alkoxycarbonyl.

[0196] In one embodiment, X1 corresponds to groups corresponding to Formula 4:wherein R40 is hydrogen, optionally substituted alkyl, or optionally substituted alkylene, R41 is hydrogen, optionally substituted alkyl, or optionally substituted alkylene, R42 is hydrogen, optionally substituted alkyl, optionally substituted alkylene, or together with R43 is =CR44R45, and R43 is hydrogen, optionally substituted alkyl, optionally substituted alkylene, or together with R42 is =CR44R45 wherein R44 is cyano and R45 is acyl or alkoxycarbonyl. For example, in one such embodiment R40 is alkoxyalkyl, R41 is hydrogen, R42 and R43 together are =CR44R45 wherein R44 is cyano and R45 is alkoxycarbonyl.

[0197] In one embodiment , X1 is selected from groups corresponding to Formula 4A: wherein R40 is alkoxyalkyl, R44

[0198] In one embodiment , X1 is selected from groups corresponding to Formula 4B:wherein R40 is alkoxyalkyl, R

[0199] In one embodiment, X1 is selected from groups corresponding to Formula 5:or alkoxy, each A3 is independently hydroxyl or alkoxy, A4 is hydroxyl or alkoxy, each k is independently 0- 3, and the dashed lines indicate a single or double bond.

[0200] In one embodiment, X1 is selected from groups corresponding to Formula 5A:wherein each A10 is independently hydrogen or alkyl, A11 is hydrogen, hydroxyl or alkoxy, and p is 1-3.

[0201] In one embodiment, X1 is selected from groups corresponding to Formula 5B:wherein each A10 is independently hydrogen or alkyl, A11 is hydrogen, hydroxyl or alkoxy, and p is 1-3.

[0202] In one embodiment, X1 is selected from groups corresponding to Formula 5Cwherein each A10 is independently hydrogen or alkyl, and p is 1-3.

[0203] In one embodiment, X1 is selected from groups corresponding to Formula 5Dwherein each A10 is independently hydrogen or alkyl, and p is 1-3.

[0204] In certain embodiments, X1 is selected from 1-(4-Methoxyphenyl)-3-(4-tert- butylphenyl)-1,3-propanedione, tris-biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl- N,N-dimethylammonium)-2-hydroxypropane-1-sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3- phenylprop-2-enoate, 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate, hexyl 2-[4- (diethylamino)-2-hydroxybenzoyl]benzoate, 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino)benzoate, 2-phenyl-3H-benzimidazole-5-sulfonic acid, 2-ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4-methoxyphenyl)(2- hydroxyphenyl)methanone, (2-hydroxy-4-methoxyphenyl)(phenyl)methanone, 3,3,5- trimethylcyclohexyl 2-hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2-ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2- hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2-hydroxy- N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4-[(Z)-[7,7- Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3-benzotriazol- 2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4-methoxyphenyl)-1,3,5-triazine-2,4- diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3- benzimidazole-4-sulfonate), 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3- tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2-ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine-2,4- diyl)bis(azanediyl)]dibenzoate, 3-Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 3-(3,4,5-trimethoxybenzylidene)-2,4-pentanedione, diethylhexylsyringylidene malonate, diethylhexyl-2,6-naphthalate, butyloctyl salicylate, tridecyl salicylate, benzotriazolyl dodecyl p-cresol, bis(cyano butylacetate) anthracenediylidene, phenoxyethyl caprylate, tris(PPG-3 benzyl ether) citrate or a derivative thereof.

[0205] The "radical derived from” a given compound is the compound wherein a hydrogen is removed at the point of attachment to the repeating unit or linker, and the hydrogen is replaced with a bond to said repeating unit or linker. Accordingly, the variable groups (e.g., XA, XB, and / or X) may be attached to the repeating unit or linker at any position by replacement of hydrogen atom on variable groups (e.g., XA, XB, and / or X) with a covalent bond to the repeating unit or linker. In particular embodiments, the variable groups (e.g., XA, XB, and / or X) may be covalently attached to the repeating unit or linker by any means without substantially altering its functional character. For example, the covalent attachment (e.g., by replacement of a hydrogen atom with a covalent bond) may substantially retain one or more characteristic properties of said compound.

[0206] In some embodiments, compositions of the invention comprise two or more different polymers each of which is as defined herein. For example, two or more different polymers each with different variable groups (e.g., XA, XB, and / or X).

[0207] In the particular embodiments, the polymeric ROS agent is a compound of the Formula Ya: (OH)δwherein α is an integer from 1 to 5; Rβ is C1-C10 alkyl; each Rγ is independently C1- C10 alkyl; and each δ is independently an integer from 1 to 4.

[0208] In the particular embodiments, the polymeric ROS agent is a compound of the Formula Yb: CH3CH3CH3Rγwherein α is an integer from 1 to 5; Rβ is C1-C10 alkyl; and each Rγ is independently C1-C10 alkyl.

[0209] In the particular embodiments, the polymeric ROS agent is a compound of the Formula Yb: CH3CH3CH3wherein RβC1-C6 alkyl.

[0210] In the particular embodiments, the polymeric ROS agent is a compound of the Formula Yc:CH3CH3CH3Si O Si O Si CH3wherein α is an

[0211] In the particular embodiments, the polymeric ROS agent is a compound of the Formula Y: CH3CH3CH3

[0212] In the particular embodiments, the polymeric ROS agent is a compound of the Formula Za:CH3CH3CH3wherein ε is an integer

[0213] In the particular embodiments, the polymeric ROS agent is a compound of the Formula Za: CH3CH3CH3wherein ε is an integer from 2 to 4; and Rζis C2-C6 alkyl.

[0214] In the particular embodiments, the polymeric ROS agent is a compound of the Formula Zb:CH3CH3CH3Si O Si O Si CH3wherein ε is an integer from 1 to 5; optionally from 2 to 4.

[0215] In the particular embodiments, the polymeric ROS agent is a compound of the Formula Z: CH3 CH3 CH3

[0216] Inof the Formula Y:CH3CH3CH3Si O Si O Si CH3or a compound of the Formula Z: CH3CH3CH3The Free ROS Agent

[0217] Compositions of the invention may comprise a free ROS agent as part of the antioxidant system.

[0218] In some embodiments, the free ROS agent may be any suitable ROS capturer (e.g., any compound with an ROS capture IC50 of 10 mM or less). For example, the free ROS agent might be any antioxidant which is known in the art.

[0219] In particular embodiments, the free ROS agent may be a polyphenol or a carotenoid, or derivatives and / or combinations thereof.

[0220] In particular embodiments, the free ROS agent may be a polyphenol, such as a flavonoid (e.g., a flavonol or flavone), a xanthene , a xanthone (e.g., mangiferin), or a stilbenoid (e.g., resveratrol), or derivatives and / or combinations thereof.

[0221] In particular embodiments, the free ROS agent may be a carotenoid, such as lycopersene, phytofluene, lycopene, hexahydrolycopene, torulene, α-zeacarotene, α- carotene, β-carotene, γ-carotene, δ-carotene, ε-carotene, or ζ-carotene, or derivatives and / or combinations thereof.

[0222] In more particular embodiments, the free ROS agent is catechin, gallocatechin, catechin-3-gallate, gallocatechin-3-gallate, epicatechin, epigallocatechin, epicatechin-3-gallate, epigallocatechin-3-gallate, flavan-4-ol, flavan-3,4-diol, leucoanthocyanidin, proanthocyanidins, luteolin, apigenin, tangeritin, quercetin, quercitrin, rutin, kaempferol, kaempferitrin, astragalin, naringenin, sophoraflavonoloside, myricetin, fisetin, isorhamnetin, pachypodol, rhamnazin, hesperetin, hesperidin, eriodictyol, homoeriodictyol, taxifolin, dihydroquercetin, dihydrokaempferol, anthocyanidins, cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin, phytoestrogens, genistein, daidzein, glycitein, equol, lonchocarpane, laxiflorane, calophyllolide, dalbergichromene, coutareagenin, dalbergin, nivetin, morin, trans- stilbene, cis-stilbene, diethylstilbestrol, α-methylstilbene, resveratrol, pterostilbene, trimethylstilbenes, dimethylstilbene, stilbamidine, 4,4'-diaminostilbene-2,2'-disulfonic acid, stilbene glycosides, hydroxyxanthone, xanthenone, xanthone carboxylic acid, xanthone glycosides, xanthone alkaloids, xanthone dimers, xanthonolignoids, isomorellin, gentisin, 1,3,6-trihydroxyxanthone, 3,6-dihydroxyxanthone, 1,5- dihydroxyxanthone, 1,7-dihydroxyxanthone, 2,3-dihydroxyxanthone, norathyriol, mangiferin, swerchirin, isojacareubin, or derivatives and / or combinations thereof. In particular embodiments, the free ROS agent is quercetin, rutin, naringenin, naringin, mangiferin, luteolin, luteolin glycoside, hesperidin, apigenin, or derivatives and / or combinations thereof. More particularly, the free ROS agent is quercetin, naringenin, mangiferin, luteolin, resveratrol, or derivatives and / or combinations thereof.

[0223] In particular embodiments, the free ROS agent comprises a combination of luteolin, naringenin, apigenin, and / or hesperidin. More particularly, the free ROS agent may comprise a combination of luteolin, naringenin, apigenin, and hesperidin.

[0224] In particular embodiments, the free ROS agent comprises a combination of quercetin and luteolin.

[0225] In other particular embodiments, the free ROS agent comprises a combination of apigenin and luteolin.

[0226] In some embodiments, the free ROS agent is quercetin.

[0227] In some embodiments, the free ROS agent is luteolin.

[0228] The free ROS agent may be one of the compounds listed herein as suitable free ROS agents but in a derivatized form. The derivative might be a chemically modified version of a compound named herein which substantially retains one or more characteristic properties of said compound (e.g., retains substantially the same ROS capture IC50). In certain embodiments, the derivative might be an ether, ester, amide, sulfide, or glycoside of the compound. In particular embodiments, the derivative may be an alkyl (e.g., C1-C10 alkyl) ether, heteroalkyl ether, aryl ether, or heteroaryl ether; or alkyl (e.g., C1-C10 alkyl) ester or heteroalkyl ester; or alkyl (e.g., C1-C10 alkyl) amide or heteroalkyl amide; or alkyl (e.g., C1-C10 alkyl) sulfide, heteroalkyl sulfide, aryl sulfide, or heteroaryl sulfide; or glycoside of the compound.

[0229] The compositions of the invention comprise the free ROS agent (e.g., any free ROS agent described herein, or combinations or derivatives thereof). The compositions of the invention may comprise any amount of the free ROS agent (e.g., any amount of the free ROS agent which is detectable within the limits of normal measurement methods).

[0230] A desirable function of the free ROS agent in the compositions of the invention may be to provide ROS capture. Accordingly, in certain embodiments, the free ROS agent has an ROS capture IC50 which is suitable to provide effective ROS capture. In some embodiments, the free ROS agent has an ROS capture IC50 of no more than 10 mM; particularly, no more than 5 mM; particularly, no more than 4 mM; particularly, no more than 3 mM; particularly, no more than 2 mM; particularly, no more than 1 mM; particularly, no more than 500 µM; particularly, no more than 400 µM; particularly nomore than 300 µM; particularly, no more than 200 µM; particularly, no more than 100 µM; particularly, no more than 50 µM; particularly, no more than 40 µM; particularly, no more than 30 µM; particularly, no more than 20 µM; particularly, no more than 10 µM; particularly, no more than 5 µM; particularly, no more than 4 µM; particularly, no more than 3 µM; particularly, no more than 2 µM; particularly, no more than 1 µM. For example, the free ROS agent may have an ROS capture IC50 of no more than 200 µM.

[0231] A desirable function of the free ROS agent in the compositions of the invention may be to provide ROS capture. Accordingly, in certain embodiments, the compositions of the invention comprise an effective amount of the free ROS agent to provide ROS capture. In some embodiments, compositions of the invention may comprise a concentration of the free ROS agent which is at least a quarter of the ROS capture IC50 of said free ROS agent. More particularly, the concentration of said free ROS agent in the compositions of the invention may be at least half of the ROS capture IC50 of said free ROS agent. More particularly, the concentration of said free ROS agent in the compositions of the invention may be at least equal to the ROS capture IC50 of said free ROS agent. More particularly, the concentration of said free ROS agent in the compositions of the invention may be at least equal to 10 times the ROS capture IC50 of said free ROS agent. More particularly, the concentration of said free ROS agent in the compositions of the invention may be at least equal to 100 times the ROS capture IC50 of said free ROS agent. More particularly, the concentration of said free ROS agent in the compositions of the invention may be at least equal to 1000 times the ROS capture IC50 of said free ROS agent. More particularly, the concentration of said free ROS agent in the compositions of the invention may be at least equal to 1500 times the ROS capture IC50 of said free ROS agent. More particularly, the concentration of said free ROS agent in the compositions of the invention may be at least equal to 1750 times the ROS capture IC50 of said free ROS agent. For example, the concentration of the free ROS agent in the compositions of the invention may be at least equal to 1000 times the ROS capture IC50 of said free ROS agent (e.g., where the ROS capture IC50 of a given free ROS agent is 1 μM the concentration of said free ROS agent in the composition of the invention may be at least 1 mM).

[0232] Where the free ROS agent is a combination (e.g., a combination of compounds), the respective concentrations of each element of the combination may beat least equal to a multiple of the ROS capture IC50 (e.g., a multiple described above) of each of said respective elements. Alternatively, or in addition, the concentration of the combination of compounds taken as a whole is at least equal to a multiple of the ROS capture IC50 of said combination.

[0233] In some embodiments, the compositions of the invention comprise the free ROS agent, wherein the total amount of the free ROS agent in the composition is from about 0.001% to about 20%, particularly from about 0.01% to about 10%, particularly from about 0.1% to about 5%, particularly from about 0.2% to about 4%, particularly from about 0.3% to about 3%, particularly from about 0.5 % to about 2.5% particularly from about 1% to about 2%, (by weight) of the composition. For example, the total amount of the free ROS agent in the compositions of the invention might be from about 1% to about 2% (by weight) of the composition.

[0234] In particular embodiments, the free ROS agent may comprise two or more free ROS agents described above. In any embodiment where there are two or more free ROS agents, all weight percentages of the free ROS agents expressed above relate to the sum total of the weight percentages of each of the free ROS agents.

[0235] In particular embodiments a further advantageous characteristic of the free ROS agent may be that the free ROS agent is substantially non-absorbed. Accordingly, the free ROS agent may of be a suitable molecular weight to reduce the likelihood that the free ROS agent will permeate the skin into systemic circulation. For example, in certain embodiments, the free ROS agent has a molecular weight of at least 100 Da; particularly, at least 200 Da; particularly, at least 300 Da; particularly, at least 400 Da; particularly, at least 500 Da; particularly, at least 600 Da; particularly, at least 700 Da; particularly, at least 800 Da; particularly, at least 900 Da; particularly, at least 1000 Da; particularly, at least 1100 Da; particularly, at least 1200 Da; particularly, at least 1300 Da; particularly, at least 1400 Da; particularly, at least 1500 Da; particularly, at least 1600 Da; particularly, at least 1700 Da; particularly, at least 1800 Da; particularly, at least 1900 Da; particularly, at least 2000 Da. For example, the free ROS agent may be any suitable free ROS agent defined herein having a molecular weight of at least 500 Da.

[0236] Alternatively, or in addition, in certain embodiments the free ROS agent may be encapsulated. Other Components of the Compositions of the Invention

[0237] The compositions of this invention can further comprise one or more additional components. For example, the compositions of the invention may further comprise one or more conventional cosmetic additives and / or adjuvants. In some embodiments, compositions of the invention further comprise water, oils, fats, organic solvents, carriers, thickeners (e.g., ionic or non-ionic thickeners), softeners, opacifiers, stabilizers, film-formers, emulsifiers, emollients, silicones, hydroxy acids, anti-foaming agents, moisturizers, fragrances, preservatives, surfactants, fillers, sequestering agents, polymers, propellants, basifying or acidifying agents, buffering agents, chelating agents, colorants, dyes, self-tanning agents, performance enhancers, sensory enhancers, powders, skin brightening agents, anti-acne agents, anti-aging agents, barrier repair agents, resurfacing agents, oil control agents, exfoliating agents, anti-inflammatory agents, natural extracts, humectants, or any other ingredient usually used in the cosmetics and / or dermatological field, or any combinations thereof.

[0238] An exemplary composition of the invention may comprise additional components in the following amounts: Solvents and / or Carriers 20 – 80 wt%

[0239] Suitable emollients which may be incorporated into compositions of the invention include hydrocarbon-based oils (e.g., liquid triglycerides of fatty acids optionally containing from 4 to 10 carbon atoms, such as heptanoic or octanoic acid triglycerides; or sunflower oil, corn oil, soybean oil, marrow oil, grapeseed oil, sesame seed oil, hazelnut oil, apricot oil, macadamia oil, arara oil, coriander oil, castor oil, or avocado oil), caprylic / capric acid triglycerides (e.g., jojoba oil, shea butter oil and caprylyl glycol), esters and ethers of fatty acids (e.g., PurCellinTMoil, 2-octyldodecyl stearate, 2-octyldodecyl erucate, isostearyl isostearate), hydroxylated esters (e.g., isostearyl lactate, octyl hydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate, or triisocetyl citrate), fatty alcohol heptanoates, fatty alcohol octanoates, fatty alcohol decanoates, polyol esters (e.g., propylene glycol dioctanoate, neopentyl glycol diheptanoate, or diethylene glycol diisononanoat), pentaerythritol esters (e.g., pentaerythrityl tetraisostearate, or isopropyl lauroyl sarcosinate), linear or branched hydrocarbons (e.g., volatile or non-volatile liquid paraffins, petroleum jelly, polydecenes, isohexadecane, isododecane, hydrogenated polyisobutene such as ParleamTMoil), fluoro oils that are partially hydrocarbon-based and / or silicone-based, silicone oils (e.g., polydimethylsiloxanes (PDMS), cyclopolydimethylsiloxanes (cyclomethicones) such as cyclohexadimethylsiloxane and cyclopentadimethylsiloxane, or polydimethylsiloxanes comprising alkyl, alkoxy or phenyl groups), phenyl silicones (e.g., phenyl trimethicones, phenyl dimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyl dimethicones, diphenylmethyldiphenyltrisiloxanes or 2-phenylethyl trimethylsiloxy silicates), and polymethylphenylsiloxanes, and combinations thereof.

[0240] In particular embodiments, the compositions of the invention comprise an emollient. Advantageously, compositions of the invention comprising emollients may be formulated as anhydrous formulations having improved stability. More particularly, in certain embodiments the emollient may comprise isododecane, isohexadecane, C12- C15 alkyl benzoate, coco caprylate caprate, caprylic / capryl triglyceride, isopropyl myristate, octyldodecyl, neopentonate, ethylhexyl palmitate, dicaprylyl carbonate, hexyl laurate, dibutyl adipate, isopropyl palmitate, and / or phenethyl benzoate. More particularly, in certain embodiments the emollient may comprise isododecane, isohexadecane, C12-C15 alkyl benzoate, coco caprylate caprate, caprylic / capryltriglyceride, isopropyl myristate, octyldodecyl, neopentonate, ethylhexyl palmitate, dicaprylyl carbonate, hexyl laurate, dibutyl adipate, and / or isopropyl palmitate. For example, the emollient may comprise hexyl laurate, dicaprylyl carbonate, isopropyl lauroyl sarcosinate, and / or isohexadecane; optionally, the emollient may comprise hexyl laurate, dicaprylyl carbonate, isopropyl lauroyl sarcosinate, and isohexadecane.

[0241] In particular embodiments, the emollient may be present in a composition of the invention at a concentration of from 2% to 30% by weight of the composition; more particularly, from 5% to 30% by weight of the composition; more particularly, from 10% to 30% by weight of the composition; more particularly, from 15% to 30% by weight of the composition; more particularly, from 15% to 28% by weight of the composition; more particularly, from 18% to 27% by weight of the composition.

[0242] In particular embodiments, the compositions of the invention comprise a thickener. For instance, the thickener may comprise hectorite clay, glyceryl behenate, silica dimethyl silylate, and / or dimethicone / bis-isobutyl PPG-20 cross-polymer with isododecane.

[0243] In particular embodiments, the thickener may be present in a composition of the invention at a concentration of from 1% to 40% by weight of the composition; more particularly from 2% to 35%; more particularly, from 5% to 32%.

[0244] In particular embodiments, the compositions of the invention may comprise a feel enhancer such as aluminum starch octenylsuccinate. In certain embodiments, the feel enhancer may be present in a composition of the invention at a concentration of from 0.5% to 3% by weight of the composition.

[0245] Suitable humectants which may be incorporated into compositions of the invention include glycerin, propylene glycol, hyaluronic acid, sorbitol, butylene glycol, pyroglutamic acid, propanediol, urea, honey, panthenol, beta-glucan, saccharide isomerate, pentylene glycol, xylitol, methyl gluceth-20, diglycerin, trimethylglycine, glycereth-26, sodium hyaluronate, xylitylglucoside, anhydroxylitol, and combinations thereof.

[0246] Suitable preservatives which may be incorporated into compositions of the invention include parabens (e.g., methylparaben, ethylparaben, propylparaben, butylparaben), phenoxyethanol, formaldehyde and formaldehyde releasing agents (e.g.,quaternium-15, DMDM hydantoin, imidazolidinyl urea, diazolidinyl urea), isothiazolinones (e.g., methylisothiazolinone), benzoic acid and salts thereof (e.g., sodium benzoate), sorbic acid and sorbates (e.g., potassium sorbate), chlorphenesin, ethylhexylglycerin, benzyl alcohol, caprylyl glycol, sodium hydroxymethylglycinate, phenethyl alcohol, glyceryl caprylate, glyceryl undecylenate, glycols (e.g., propylene glycol, hexylene glycol, decylene glycol), lactic acid, citric acid, silver citrate, copper peptides, chelating agents (e.g., disodium EDTA, tetrasodium EDTA), naturally derived preservatives (e.g., leuconostoc / radish root ferment filtrate), and combinations thereof.

[0247] Suitable emulsifiers which may be incorporated into compositions of the invention include cetearyl alcohol, ceteareth-20, glyceryl stearate, PEG-100 stearate, sorbitan stearate, sorbityl laurate, polysorbates (e.g., polysorbate 20, polysorbate 40, polysorbate 60,or polysorbate 80), ceteareth-12, cetyl palmitate, laureth-7, sodium stearoyl lactylate, steareth-2, steareth-21, glyceryl undecylenate, caprylic / capric acid triglycerides (e.g., jojoba oil, shea butter oil and caprylyl glycol), hydrogenated lecithin, PEG-8 Beeswax, sodium lauryl sulfate, sorbitan olivate, sorbitan sesquioleate, xanthan gum, lecithin, polyglyceryl-3 diisostearate, polyglyceryl-4 diisostearat, caprylyl methicone, caprylyl dimethicone, PEG / PPG-14 / 4 dimethicone , bis-PEG / PPG-20 / 20 dimethicone, PEG-8 dimethicone, cetyl PEG / PPG-10 / 1 dimethicone, bis-PEG / PPG- 14 / 14 dimethicone, lauryl PEG / PPG-18 / 18 methicone, PEG-10 dimethicone, PEG-12 dimethicone crosspolymer, PEG-12 dimethicone, PEG / PPG-18 / 18 dimethicone, PEG / PPG-20 / 20 phenylisopropyl caprylyl dimethicone, dimethicone / PEG-10 / 15 crosspolymer , PEG-15 / lauryl polydimethylsiloxyethyl dimethicone crosspolymer , PEG / PPG-19 / 19 dimethicone, lauryl PEG-9 polydimethylsiloxvethyl dimethicone, bis- isobutyl PEG / PPG-10 / 7 / dimethicone copolymer, bis-PEG / PPG-20 / 5 PEG / PPG-20 / 5 dimethicone, methoxy PEG / PPG-25 / 4 dimethicone, cetyl diglyceryl tris(trimethylsiloxy)silylethyl dimethicone, PEG-11 methyl ether dimethicone, lauryl PEG- 10 tris(trimethylsiloxy)silylethyl dimethicone, PEG / PPG-25 / 25 dimethicone, polysilicone- 11, dimethiconol stearate, polyglyceryl-3 polydimethylsiloxyethyl dimethicone , lauryl polyglyceryl-3 polydimethylsiloxyethyl dimethicone , polyhydroxystearate, polyglyceryl-3 oleate, polyglyceryl-4 olivate, polyricinoleate , polyglyceryl-3 methylglucose distearate, lauryl PEG-9 polydimethylsiloxyethyl dimethicone , polyglyceryl-2 sesquioleate, diisostearoyl polyglyceryl-3 dimer dilinoleate, polyglyceryl-10 stearate, polyglyceryl-6stearate, polyglyceryl-6 behenate polyglyceryl-6 esters, polyglyceryl-6 pentaoleate, PEG-30 dipolyhydroxystearate, polyglyceryl-2 dipolyhydroxystearate, polyglyceryl 4 diisostearate polyhydroxystearate / sebacate, acrylates / c10-30 alkyl acrylate crosspolymer, acrylates / acrylamide copolymers, sodium acrylate / sodium acryloyldimethyl taurate copolymer, carbomer, and combinations thereof.

[0248] Suitable fragrances which may be incorporated into compositions of the invention include geraniol, citronellol, phenylethyl alcohol, linalool, linalyl acetate, vanillin, limonene, citral, benzyl acetate, indole, santalol, patchoulol, bergapten, benzyl salicylate, beta-ionone, beta-damascenone, coconut aldehyde, muscone, musk ketone, ambroxide, hydroxycitronellal, irones, phenylacetaldehyde, hexenyl acetate, ethyl hexanoate, ethyl butanoate, gamma-decalactone, raspberry ketone, methyl anthranilate, hexenyl acetate, menthol, eucalyptol, zingiberene, terpinyl acetate, cedrol, and combinations thereof.

[0249] Suitable propellants include propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide, and combinations thereof.

[0250] Suitable self-tanning agents include dihydroxy-acetone.

[0251] Suitable skin brightening agents include ellagic acid, vitamin C, vitamin E, hydroxycinnamic acid, gallic acids, azelaic acid, linolic acid, tranexamic acid, ectoin, resveratrol, alpha hydroxy acids, beta hydroxy acids, poly hydroxy acids, glycolic acid, lactic acid, salicylic acid, niacinamide, ferulic acid, arbutin, alpha arbutin, retinoids, retinols, bakuchiol, bisabolol, glutathione, tetrahydropyranyloxy phenol, diacetyl boldine, hexylresorcinol, 4-butylresorcinol, phenylethyl resorcinol, dimethylmethoxy chromanyl palmitate, oxothiazolidinecarboxylic acid, dimethylmethoxy chromanol, flavones, flavanols, flavonoids, natural extracts and oils (e.g., rosehip oil, grapeseed oil, evening primrose oil, Euterpe Oleracea Fruit Oil, Oryza Sativa (Rice) Bran Oil, Ribes Nigrum (Black Currant) Seed Oil, Lavandula Hybrida Oil, Laurus Nobilis Leaf Oil, Glycyrrhiza Glabra (Licorice) Root Extract, mulberry extract, Cucumis Sativus (Cucumber) Seed Extract, Morus Alba Bark Extract, Hibiscus Sabdariffa Flower Extract, Chlorella Vulgaris / Lupinus Albus Protein Ferment, Nasturtium Officinale Flower / Leaf Extract, Citrus Limon (Lemon) Fruit Extract, Bellis Perennis (Daisy) Flower Extract, Rose Extract), and combinations and / or derivatives thereof.

[0252] In particular embodiments, compositions of the invention comprise styrene / acrylate copolymer. In certain embodiments, a composition of the invention may comprise styrene / acrylate copolymer at a concentration of from 1% to 8% by weight of the composition; more particularly, from 2% to 7%; more particularly, from 3% to 6%.

[0253] Other ingredients which may be incorporated into compositions of the invention include caffeine and aloe vera. Certain General Compositions

[0254] Certain general compositions of the invention are described below. In particular embodiments, more specific aspects of these compositions are as defined elsewhere herein. For instance, in some embodiments the free ROS agent might be quercetin, naringenin, mangiferin, luteolin, hesperidin, apigenin, or derivatives and / or combinations thereof.

[0255] In certain embodiments, the invention relates to a topical composition having a %UVA-T of no more than 10% and / or a UVA-PF of at least 30 as measured by hybrid diffuse reflectance spectroscopy, an in vivo SPF of less than 15, and comprising an antioxidant system; wherein: the antioxidant system comprises ROS agents and the ROS agents comprise a free ROS agent and a polymeric ROS agent; the free ROS agent is a polyphenol or carotenoid; the polymeric ROS is a polymer of Formula 1: X ;wherein the terminal groups, XA and XB, are each independently absent, or independently selected from X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; X wherein the repeat unit, wherein each X is independently absent hydrocarbyl, substituted hydrocarbyl, orheterocyclyl; and L is the optional linker, which may be a linker moiety or a covalent bond; and X1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties; and wherein the repeat unit of Formula 1 corresponds to any one of Formulae 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 1I, 1J, 1K, 1L, 1M, 1N or a combination thereof:wherein: L is a covalent bond or a linker covalently attaching X1 to the remainder of the structure, X1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties, each of X2 – X7 is hydrocarbyl or optionally substituted hydrocarbyl, andeach of X8, X9 or X10 is X1, hydrogen, hydrocarbyl or substituted hydrocarbyl.

[0256] In certain embodiments the invention relates to, a topical composition having a %UVA-T of no more than 5%, and comprising an antioxidant system, wherein the antioxidant system comprises ROS agents; wherein the ROS agents comprise a free ROS agent and a polymeric ROS agent; wherein the polymeric ROS agent is a polymer of Formula 1: X (Formula 1);XA and XB, are each independently absent, or independently selected from X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; X wherein the repeat unit, wherein each X is independently absenthydrocarbyl, substituted hydrocarbyl, or heterocyclyl; and L is the optional linker, which may be a linker moiety or a covalent bond; and X1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties;wherein the repeat unit of Formula 1 corresponds to any one of Formulae 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 1I, 1J, 1K, 1L, 1M, 1N or a combination thereof:wherein: L is a covalent bond or a linker covalently attaching X1 to the remainder of the structure, X1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties,each of X2 – X7 is hydrocarbyl or optionally substituted hydrocarbyl, and each of X8, X9 or X10 is X1, hydrogen, hydrocarbyl or substituted hydrocarbyl. wherein at least one of XA, XB, and X is X1; wherein the free ROS agent is a polyphenol or carotenoid.

[0257] In certain embodiments the invention relates to, a topical composition having an in vivo SPF of less than 15, and comprising an antioxidant system, wherein the antioxidant system comprises ROS agents; wherein the ROS agents comprise a free ROS agent and a polymeric ROS agent; wherein the polymeric ROS agent is a polymer of Formula 1: X (Formula 1);XA and XB, are each independently absent, or independently selected from X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; X wherein the repeat unit, wherein each X is independently absenthydrocarbyl, substituted hydrocarbyl, or heterocyclyl; and L is the optional linker, which may be a linker moiety or a covalent bond; and X1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide,acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties; wherein the repeat unit of Formula 1 corresponds to any one of Formulae 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 1I, 1J, 1K, 1L, 1M, 1N or a combination thereof:wherein: L is a covalent bond or a linker covalently attaching X1 to the remainder of the structure,X1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties, each of X2 – X7 is hydrocarbyl or optionally substituted hydrocarbyl, and each of X8, X9 or X10 is X1, hydrogen, hydrocarbyl or substituted hydrocarbyl, at least one of XA, XB, and X is X1; and the free ROS agent is a polyphenol or carotenoid.

[0258] In certain embodiments, the invention relates to a topical composition comprising an antioxidant system; wherein the antioxidant system comprises ROS agents and the ROS agents comprise a free ROS agent and a polymeric ROS agent; the free ROS agent is quercetin, naringenin, mangiferin, luteolin, hesperidin, apigenin, or derivatives and / or combinations thereof; the polymeric ROS agent is a polymer of: (a) Formula Ya: (OH)δwherein α is C1-C10 alkyl; and each δ is independently an integer from 1 to 4; or (b) Formula Za:CH3CH3CH3O RζSi O Si O Si wherein ε is an integer

[0259] In certain embodiments, the invention relates to a topical composition comprising an antioxidant system; wherein: the antioxidant system comprises ROS agents and the ROS agents comprise a free ROS agent; the free ROS agent is quercetin, naringenin, mangiferin, luteolin, hesperidin, apigenin, or derivatives and / or combinations thereof; and the topical composition comprises no more than two different organic UV filters selected from 1-(4-Methoxyphenyl)-3-(4-tert-butylphenyl)-1,3- propanedione, tris-biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl-N,N- dimethylammonium)-2-hydroxypropane-1-sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3- phenylprop-2-enoate, 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate, hexyl 2-[4- (diethylamino)-2-hydroxybenzoyl]benzoate, 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino)benzoate, 2-phenyl-3H-benzimidazole-5-sulfonic acid, 2-ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4-methoxyphenyl)(2- hydroxyphenyl)methanone, (2-hydroxy-4-methoxyphenyl)(phenyl)methanone, 3,3,5- trimethylcyclohexyl 2-hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2-ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2- hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2-hydroxy- N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4-[(Z)-[7,7- Dimethyl-2-oxo-1-(sulfomethyl)-3-bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3-benzotriazol- 2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4-methoxyphenyl)-1,3,5-triazine-2,4- diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3- benzimidazole-4-sulfonate), 2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3- tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2- ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine-2,4- diyl)bis(azanediyl)]dibenzoate, 3-(3,4,5-trimethoxybenzylidene)-2,4-pentanedione, diethylhexylsyringylidene malonate, diethylhexyl-2,6-naphthalate, butyloctyl salicylate, tridecyl salicylate, benzotriazolyl dodecyl p-cresol, bis(cyano butylacetate) anthracenediylidene, phenoxyethyl caprylate, tris(PPG-3 benzyl ether) citrate and / or 3- Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, or a salt of any of the aforementioned. Such compositions may be of particular interest where a composition is desired without requiring a polymeric ROS agent. Consumer Formulations

[0260] Compositions of the invention may be prepared by any suitable method which is known in the art. For instance, compositions of the invention might be prepared by routine admixture and / or emulsification procedures which are known in the art.

[0261] The compositions of the invention are particularly formulated as topical formulations. Suitable topical formulations may be liquids or solids. Suitable topical formulations include, for example, oil-in-water (o / w) emulsions, water-in-oil (w / o) emulsions, multiple emulsions (e.g., water-in-oil-in-water emulsions or oil-in-water-in-oil emulsions), microemulsions, high internal phase emulsions (HIPE), water-in-silicone emulsions, PET emulsions, Pickering emulsions, anhydrous lotions or creams, hydrogels, alcoholic gels, lipogels, mono-phase or multi-phase solutions, foams, ointments, plasters, suspensions, powders, creams, cleansers, soaps and other usual compositions.

[0262] In various embodiments, compositions of the invention are topical compositions which are suitable for use as an anti-aging skincare product.

[0263] In certain embodiments, the compositions of the invention are formulated as anhydrous formulations. Advantageously, when formulated as anhydrous formulations, compositions of the invention may provide a rich and luxurious texture; quick absorption; and non-greasy, smooth, and silky skin feel. Consumer Product

[0264] The compositions of the invention may be packaged in any suitable container. Suitable containers include bottles, jars, tubes, pump dispensers, dropper bottles, pots, squeeze tubes, stick containers, roll-on bottles, airless pump bottles, aerosol cans, spray bottles, tins, pump jars, wand applicators, sachets, and foamer bottles. Methods

[0265] The present invention is also directed to methods for protecting an animal tissue (e.g., human skin) from ultraviolet radiation (e.g., UVA) and to methods of absorbing ultraviolet light. Such methods encompass applying a composition of the invention to an animal tissue (e.g., human skin).

[0266] The compositions of the invention are suitable for topical application (e.g., on human skin). Accordingly, in one aspect the invention relates to a method of using any of the compositions described herein, the method comprising applying the composition topically (e.g., to human skin). In some embodiments, the composition is applied topically at least daily. In particular embodiments, the composition is applied topically at least twice a day, particularly, the composition is applied at least three times a day, particularly the composition is applied at least three times a day, particularly the composition is applied at least four times a day, particularly the composition is applied at least five times a day. In some embodiments, the compositions of the invention are applied during daylight hours or at night. In some embodiment, the compositions of the invention are applied before or after exposure (e.g., of the skin) to the sun.

[0267] In certain embodiments, the compositions of the invention are applied as a photo-aging inhibition composition and not as a sunscreen composition. Synthesis of the Polymeric ROS Agent

[0268] The polymeric ROS agents described herein can be synthesized using polymer-chemistry techniques and reactions well-known to those with ordinary skill in the field. Polymer backbones that can be conjugated to X1 groups defined herein include, but are not limited to, polyesters, polyethers, polyurethanes, polycarbonates, polysiloxanes, polyacrylates, polyalcohols, polyolefins, polyvinylpyrrolidones, polyoxazolines, polystyrenes, polysacharrides, polymaleic acids, polylactones, polyamides, naturally occurring polymers (e.g., chitosan), and copolymers thereof.

[0269] Specific polymeric ROS agents and their accompanying syntheses are exemplified in the "Examples” section below.

[0270] The X1 groups described herein can be introduced into the polymeric ROS agents by incorporating monomers conjugated to X1 groups during the polymerization process or by conjugating X1 groups to pre-formed polymers. In the former approach, X1 moieties are conjugated to a polymerizable group and incorporated into polymers during polymerization (see, for example, “Principles of Polymerisation” by George Odian, 2004). In the latter approach, a polymer is formed first and then X1 moieties are appended to backbone or endgroups of the polymer by standard conjugation techniques (Eva Blasco, Michael B. Sims, Anja S. Goldmann, Brent S. Sumerlin, and Christopher Barner-Kowollik; Macromolecules; 2017; 50 (14); 5215-5252). In either approach, the number and positioning of X1 moieties across the polymer backbone can be controlled. Similarly, polymers can be of many different architectures including linear, branched, brush, crosslinked, matrix, and dendrimer. Additionally, the molecular weight of the polymer can be tailored to impact its performance and safety.

[0271] A reference document describing common techniques for copolymerization of acrylate monomers is D'Acunzo, F. & Masci, G., 2021, Playing construction with the monomer toy box for the synthesis of multi‐stimuli responsive copolymers by reversible deactivation radical polymerization protocols, Journal of Polymer Science, 59(24), pp.3059-3083.

[0272] A reference document is Kim, J. G., & Shin, H. G., 2022, Functional Acrylate Polymer Synthesis: Postpolymerization Modification Approach. Macromolecular Research, 30(11), pp.757-765 which describes common techniques for post polymerization functionalization of polyacrylates.

[0273] Reference documents are Chruściel, J. J., 2020, Hydrosilyl-Functional Polysiloxanes: Synthesis, Reactions and Applications, Reactive and Functional Polymers Volume One: Biopolymers, Polyesters, Polyurethanes, Resins and Silicones, pp.329-414, Chicago and Ren, Z., & Yan, S., 2016, Polysiloxanes for optoelectronic applications, Progress in Materials Science, 83, pp.383-416, which describe common techniques for copolymerization of siloxane monomers.

[0274] A reference document is Boutevin, B., Guida-Pietrasanta, F., & Ratsimihety, A., 2000, Side group modified polysiloxanes. Silicon-Containing Polymers: The Science and Technology of Their Synthesis and Applications, pp.79-112 which describes common techniques for post polymerization functionalization of polysiloxanes.

[0275] Williams, C.K., 2007, Synthesis of functionalized biodegradable polyesters, Chemical Society Reviews, 36(10), pp.1573-1580 and Tian, H., Tang, Z., Zhuang, X., Chen, X. and Jing, X., 2012, Biodegradable synthetic polymers: Preparation, functionalization and biomedical application, Progress in Polymer Science, 37(2), pp.237-280 teach common techniques for copolymerization of polyester-forming monomers.

[0276] Kavand, A., Anton, N., Vandamme, T., Serra, C.A. and Chan-Seng, D., 2020, Synthesis and functionalization of hyperbranched polymers for targeted drug delivery, Journal of Controlled Release, 321, pp.285-311 teaches common techniques for post-polymerization functionalization of polyesters.

[0277] Jayakannan, M. and Ramakrishnan, S., 2001, Recent developments in polyether synthesis, Macromolecular Rapid Communications, 22(18), pp.1463-1473 and Brocas, A.L., Mantzaridis, C., Tunc, D. and Carlotti, S., 2013, Polyether synthesis: From activated or metal-free anionic ring-opening polymerization of epoxides to functionalization, Progress in Polymer Science, 38(6), pp.845-873 teach common techniques for copolymerization of polyether-forming monomers.

[0278] Thomas, A., Müller, S.S. and Frey, H., 2014, Beyond poly (ethylene glycol): linear polyglycerol as a multifunctional polyether for biomedical and pharmaceutical applications, Biomacromolecules, 15(6), pp.1935-1954 teaches common techniques for post polymerization functionalization of polyethers. EXAMPLES

[0279] Compositions and methods of the invention are illustrated by the following non-limiting examples. Example 1 – Photostability of UVA Absorbing Compounds

[0280] %UVA-T may be determined in vitro by measuring the absorbance of UV radiation through polymethyl methacrylate (PMMA) plates (5 cm x 5 cm, roughed by sandblasting, e.g. Helioscreen SB6). A blank PMMA plate is prepared by coating the plate with a thin layer of glycerin, and the blank absorbance spectrum is recorded. Next, multiple PMMA plates are coated with sample formulation, about 1.2 – 1.3 mg / cm2. The application of the test composition is performed first using circular motions followed by vertical and horizontal strokes, over the course of about 1 minute total. The plates are then allowed to dry at about 30°C. The blank-corrected UV absorbance spectrum of each plate is recorded using a suitable spectrometer (e.g. Labsphere UV-2000S) and an initial (pre-irradiation) in vitro %UVA-T value (average transmission between 320 – 400 nm) for each sample plate is calculated, as is the in vitro UVA-PF using the calculation described in ISO 24443. The sample plates are subsequently exposed to solar simulator radiation (Ametek Atlas CPS+ with xenon lamp and daylight filter set, 750 W / m2300-800nm) to evaluate photostability, and the %UVA-T is re-measured to yield the final %UVA-T result (post-irradiation). The final %UVA-T result is the average transmission of the UV-irradiated sample plates over the wavelengths 320 – 400 nm. The absorbance spectra before and after irradiation) may also be used to calculate the UVA protection factor (UVA-PF) as described in ISO 24443. Example 2 – Synthesis of Exemplary Polymeric ROS Agents

[0281] Various polymeric ROS agents are described below.Example 2.1 - Preparation of AB43301 DMS-H03 OH H Si O Si O Si HProcedure for the Preparation of Compound 2

[0282] To a solution of compound 1a (19.0 g, 69.79 mmol, 1.0 eq) in toluene (200 mL) were added compound 1C (7.97 g, 69.79 mmol, 1.0 eq) and TBAB (9.0 g, 27.92 mmol, 0.4 eq). The reaction mixture was stirred at 106oC for 16 hours under N2. LC-MS indicated a new peak and the starting material was gone. The mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM / MeOH = 6%) to afford compound 2 (8.0 g, 30%) as colorless oil. TLC: DCM / MeOH = 10 / 1 Rf (Compound 1a) = 0.2 Rf (Compound 2) = 0.3 LC-MS: 387 [M+1]+Procedure for the Preparation of AB43301

[0283] To a solution of compound 2 (3.0 g, 7.76 mmol, 2.0 eq) in toluene (30 mL) were added DMS-H03 (1.96 g, 3.88 mmol, 1.0 eq) and H2PtCl6.6H2O (100.47 mg, 0.19 mmol, 0.05 eq). The reaction mixture was stirred at 90oC for 16 hours under N2. The mixture was filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM / MeOH = 7%) to afford AB43301 (4.0 g, 40%) as yellow solid.1H NMR (400 MHz, Chloroform-d) δ 12.00 (d, J = 4.0 Hz, 2H), 7.36-7.28 (m, 4H), 6.92 – 6.84 (m, 4H), 6.15 – 6.00 (m, 4H), 5.43 – 5.22 (m, 2H), 4.23-3.95 (m, 6H), 3.65 – 3.39 (m, 8H), 3.09 (dd, J = 17.6, 13.2 Hz, 2H), 2.79 (dd, J = 17.2, 3.3 Hz, 2H), 1.61 (dd, J = 14.4, 7.4 Hz, 4H), 0.94 (dt, J = 19.6, 7.6 Hz, 2H), 0.57 – 0.46 (m, 1H), 0.19 – -0.03 (m, 30H). Example 2.2 – Preparation of AB43302 1a HO O O O HO AcO EDCI,DM O O HO AP AcCl, TEAProcedure for the Preparation of Compound 2

[0284] To a solution of compound 1 (40.0 g, 222 mmol, 1.0 eq) in THF (400 mL) were added compound 1a (57.4 g, 666 mmol, 3.0 eq), EDCI (51.1 g, 264 mmol, 1.2 eq) and DMAP (2.71 g, 22.2 mmol, 0.1 eq) at rt. The reaction mixture was stirred for 16 hunder N2 at 60oC. The reaction was detected by LCMS. The resulting mixture was quenched with HCl (1 N, 100 mL) and extracted with EA (300 mL x 3). The combined organic layers were washed with brine (400 mL), dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 4 / 1 ~ 3 / 1) to afford compound 2 (15.0 g, 27%) as white solid. TLC: DCM / MeOH = 10 / 1 Rf (Compound 1) = 0.6 Rf (Compound 2) = 0.5 LC-MS: 249 [M+1]+1H NMR (400 MHz, Chloroform-d) δ 7.59 (d, J = 16.0 Hz, 1H), 7.12 (s，1H), 7.00 (dd, J = 8.0, 2.0 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.37 (s, 1H), 6.27 (d, J = 16 Hz, 1H), 6.10 (s, 1H), 5.89 – 5.76 (m, 1H), 5.11 – 4.96 (m, 2H), 4.22 (m, 2H), 2.17 (q, J = 7.2 Hz, 2H), 1.81 (p, J = 7.2 Hz, 2H) Procedure for the Preparation of Compound 3

[0285] To a solution of compound 2 (7.35 g, 29.6 mmol, 1.0 eq) in THF (50 mL) were added TEA (14.77 g, 146 mmol, 5.0 eq) and AcCl (5.27 g, 67.16 mmol, 2.3 eq) at 0oC. The reaction mixture was stirred for 12 h under N2 at RT. The reaction solution was quenched with water (50 mL) and filtered directly. The filtrate was extracted with EA (150 mL x 3). The combined organic layers were washed with brine (50 mL), dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 83 / 17) to afford compound 3 (6.1 g, 62%) as yellow oil. TLC: PE / EA = 3 / 1 Rf (Compound 2) = 0.1 Rf(Compound 3) = 0.4 LC-MS: 333 [M+1]+1H NMR (400 MHz, Chloroform-d) δ 7.59 (d, J = 16.0 Hz, 1H), 7.42 – 7.32 (m, 2H), 7.20 (d, J = 8.4 Hz, 1H), 6.36 (d, J = 16.0 Hz, 1H), 5.87 – 5.74 (m, 1H), 5.10 – 4.94 (m, 2H), 4.19 (m, 2H), 2.28 (s, 6H), 2.21 – 2.11 (m, 2H), 1.84 – 1.73 (m, 2H).Procedure for the Preparation of Compound 4 To a solution of compound 3 (6.1 g, 18.36 mmol, 2.0 eq) in toluene (60 mL) were added DMS-H05 (5.99 g, 9.18 mmol, 1.0 eq) and H2PtCl6·6H2O (237 mg, 0.46 mmol, 0.05 eq) at RT. The reaction mixture was stirred for 16 h under N2 at 90oC. The reaction was detected by HPLC. The reaction solution was filtered with diatomite directly. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 4 / 1) to afford compound 4 (7.0 g, 58%) as yellow oil.1H NMR (400 MHz, Chloroform-d) δ 7.60 (d, J = 16.0 Hz, 2H), 7.43 – 7.32 (m, 4H), 7.21 (d, J = 8.4 Hz, 2H), 6.37 (d, J = 16.0, 2H), 4.22 – 4.15 (m, 4H), 2.29 (s, 12H), 1.38 (dd, m, 7H), 0.55 (m, 3H), 0.05 (d, J = 9.6 Hz, 56H). Procedure for the Preparation of AB43302

[0286] To a solution of compound 4 (7.0 g, 5.3 mmol, 1.0 eq) in MeOH (70 mL) were added NaHCO3 (18.57 g, 53 mmol, 10.0 eq) at rt. The reaction mixture was stirred for 16 h under N2 at rt. The reaction solution was filtered with celite. The filtrate was concentrated to afford AB43302 (4.63 g, 75%) as brown solid.1H NMR (400 MHz, Methanol-d4) δ 7.51 (d, J = 16.0 Hz, 2H), 6.99 (s, 2H), 6.87 (dd, J = 8.0, 2.0 Hz, 2H), 6.69 (d, J = 8.0 Hz, 2H), 6.17 (d, J = 16.0 Hz, 2H), 4.14 (m, 4H), 1.69 (s, 4H), 1.47 – 1.40 (m, 8H), 0.59 (m, 5H), 0.08 (m, 90H). Example 2.3 - Preparation of AB43303 OOO O DMS-H03 OH OH1aOH OProcedure for the Preparation of Compound 2 To a solution of 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoic acid (1, 10.0 g, 31.91 mmol, 1.0 eq) in DCM (150 mL) were added pent-4-en-1-ol (1a, 3.02 g, 35.10 mmol, 1.1 eq) and N,N-dimethylpyridin-4-amine (389.9 mg, 3.19 mmol, 0.1 eq ) at RT. Then to the solution was added N,N'-dicyclohexylmethanediimine (7.90 g, 38.30 mmol, 1.2 eq) slowly while stirring at RT. The reaction mixture was stirred for 16 h under N2at RT. The reaction solution was quenched with water (150 mL) and filtered directly. The filter cake was continuously rinsed with DCM until the filter cake turned white. The filtrate was extracted with DCM (150 mL x 3). The combined organic layers were washed with brine (150 mL), dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 20 / 1) to afford compound 2 (10.82 g, 89%) as yellow oil. TLC: PE / EA = 10 / 1 Rf (Compound 1) = 0.1 Rf (Compound 2) = 0.4 LC-MS: 382.2 [M+1]+1H NMR (400 MHz, Chloroform-d) δ 8.07 (m, 1H), 7.61 (m, 1H), 7.53 (m, 1H), 7.37 (m, 1H), 6.90 (d, J = 9.2, 1H), 6.17 (d, J = 2.4 Hz, 1H), 6.11 – 6.04 (m, 1H), 5.71 (m, 1H), 5.00 – 4.88 (m, 2H), 4.14 (td, J = 6.5, 1.2 Hz, 2H), 3.38 (q, J = 7.2 Hz, 4H), 2.03 – 1.92 (m, 2H), 1.66 – 1.57 (m, 2H), 1.18 (m, 6H). Procedure for the Preparation of AB43303

[0287] To a solution of pent-4-en-1-yl 2-[4-(diethylamino)-2- hydroxybenzoyl]benzoate (2, 7.0 g, 18.35 mmol, 1.3 eq) in toluene (70 mL) were added DMS-H03 (7.13 g, 14.12 mmol, 1.0 eq) and H2PtCl6·6H2O (365.5 mg, 0.7 mmol, 0.05 eq) at RT. The reaction mixture was stirred for 16 h under N2 at 90oC. The reaction was detected by HPLC. The reaction solution was filtered with celite directly. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 1 / 1) to afford AB43303 (5.55 g, 31%) as yellow oil.1H NMR (400 MHz, Chloroform-d) δ 12.59 (s, 2H), 8.06 (d, J = 7.6 Hz, 2H), 7.52-7.59 (m, 4H), 7.36 (d, J = 7.6 Hz, 2H), 6.89 (d, J = 9.2 Hz, 2H), 6.17 (s, 2H), 6.08 (d, J = 8.4Hz, 2H), 4.12 (t, J = 6.8 Hz, 4H), 3.37 (q, J = 7.2 Hz, 8H), 1.60-1.51 (m, 4H), 1.30-1.23 (m, 8H), 1.18 (t, J = 7.2 Hz, 12H), 0.49 (s, 4H), 0.06 (d, J = 3.6 Hz, 40H). Example 2.4 - Preparation of AB43304 DMS-H21 O O OH O H Si O Si O Si H(1, 10.0 g, 31.91 mmol, 1.0 eq) in DCM (150 mL) were added pent-4-en-1-ol (1a, 3.02 g, 35.10 mmol, 1.1 eq) and N,N-dimethylpyridin-4-amine (389.9 mg, 3.19 mmol, 0.1 eq ) at RT. Then to the solution was added N,N'-dicyclohexylmethanediimine (7.90 g, 38.30 mmol, 1.2 eq) slowly while stirring at RT. The reaction mixture was stirred for 16 h under N2 at RT. The reaction solution was quenched with water (150 mL) and filtered directly. The filter cake was continuously rinsed with DCM until the filter cake turned white. The filtrate was extracted with DCM (150 mL x 3). The combined organic layers werewashed with brine (150 mL), dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 20 / 1) to afford compound 2 (10.82 g, 89%) as yellow oil. TLC: PE / EA = 10 / 1 Rf (Compound 1) = 0.1 Rf (Compound 2) = 0.4 LC-MS: 382.2 [M+1]+1H NMR (400 MHz, Chloroform-d) δ 8.07 (d, J = 7.8, 1H), 7.61 (d, J = 7.4, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.37 (d, J = 7.6, 1H), 7.26 (s, 1H), 6.90 (d, J = 9.2, 1H), 6.17 (s, 1H), 6.11 – 6.04 (m, 1H), 5.67-5.74 (m, 1H), 5.00 – 4.88 (m, 2H), 4.14 (td, J = 6.4, 1.2 Hz, 2H), 3.38 (q, J = 7.2 Hz, 4H), 2.03 – 1.92 (m, 2H), 1.66 – 1.57 (m, 2H), 1.18 (td, J = 7.2, 1.1 Hz, 6H). Procedure for the Preparation of AB43304

[0289] To a solution of pent-4-en-1-yl 2-[4-(diethylamino)-2- hydroxybenzoyl]benzoate (2, 7.0 g, 18.35 mmol, 1.3 eq) in toluene (70 mL) were added DMS-H21 (26.0 g, 14.12 mmol, 1.0 eq) and H2PtCl6·6H2O (365.5 mg, 0.7 mmol, 0.05 eq) at RT. The reaction mixture was stirred for 16 h under N2 at 90oC. The reaction was detected by HPLC. The reaction solution was filtered with celite directly. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 1 / 1) to afford AB43304 (15.0 g, 41%) as yellow oil.1H NMR (400 MHz, Chloroform-d) δ 12.60 (s, 2H), 8.07 (d, J = 8.0 Hz, 2H), 7.59 (dd, J = 7.6, 1.6 Hz, 2H), 7.55 – 7.49 (m, 2H), 7.37 (d, J = 7.6 Hz, 2H), 6.89 (d, J = 9.2 Hz, 2H), 6.15 (s, 2H), 6.05 (d, J = 8.0, 2.4 Hz, 2H), 4.13 (t, J = 6.8 Hz, 4H), 3.38 (q, J = 7.2 Hz, 8H), 1.57 – 1.50 (m, 3H), 1.35 – 1.15 (m, 23H), 0.49 (t, J = 7.8 Hz, 4H), 0.08 (s, 937H).Example 2.5 - Preparation of AB43305 Et2N

[0290] To a solution of compound 2 (10.0 g, 26.21 mmol, 4.5 eq) in toluene (100 mL) were added HMS-501 (5.83 g, 5.83 mmol, 1.0 eq) and H2PtCl6.6H2O (150.20 mg, 0.29 mmol, 0.05 eq). The reaction mixture was stirred at 90oC for 16 hours under N2. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography, eluted with (PE / EA = 60%) to afford AB43305 (5.7 g, 20%) as colourless oil.1H NMR (400 MHz, Chloroform-d) δ 12.58 (s, 1 H), 8.03 (s, 1H), 7.63 – 7.41 (m, 2H), 7.34 (d, J = 8.0 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.12 (s, 1H), 6.02 (d, J = 8.0 Hz, 1H), 4.18 – 4.03 (m, 2H), 3.35 (s, 4H), 2.04 (s, 1H),1.56 (s, 2 H), 1.26 (s, 4H), 1.16 (s, 6H), 0.45 (s, 2H), 0.05 (s, 16H). Example 2.6 - Preparation of AB43310O O 1a HO EDCl O NMe

[0291] To a solution of 4-(Dimethylamino)cinnamic acid (1, 30.0 g, 156.88 mmol, 1.0 eq) in Pyridine (300 mL) were added pent-4-en-1-ol (1a, 33.78 g, 0.39 mol, 2.5 eq) and EDCl (48.12 mg, 0.25 mol, 0.1 eq) was stirred for 16 h under N2 at 45oC. The mixture was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 10 / 1) to afford compound 2 (19.0 g, 47%) as yellow soild. TLC: PE / EA = 5 / 1 Rf (Compound 1) = 0 Rf (Compound 2) = 0.6 LC-MS: 260.3 [M+H]+1H NMR (400 MHz, Chloroform-d) δ 7.62 (d, J = 16.0 Hz, 1H), 7.46 – 7.39 (m, 2H), 6.71 – 6.63 (m, 2H), 6.23 (d, J = 16.0 Hz, 1H),5.81-5.88 (m, 1H), 4.17 (t, J = 6.8 Hz, 2H), 3.02 (s, 6H), 2.15-2.2 (m, 2H), 1.77-1.84 (m, 2 H). Procedure for the Preparation of AB43310

[0292] To a solution of compound 2 (2.5 g, 9.64 mmol, 2.0 eq) in toluene (70 mL) were added DMS-H05 (3.1 g, 4.75 mmol, 1.0 eq) and H2PtCl6·6H2O (124.9 mg, 0.24 mmol, 0.05 eq). The reaction mixture was stirred for 16 h under N2at 95oC. The reaction was detected by HPLC. The reaction solution was filtered with celite directly.The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 10 / 1) to afford AB43310 (4.28 g, 76%) as yellow oil.1H NMR (400 MHz, Chloroform-d) δ 7.61 (d, J = 16.0 Hz, 2H), 7.45 – 7.38 (m, 4H), 6.69 – 6.62 (m, 2H), 6.22 (d, J = 16.0 Hz, 2H), 4.16 (t, J = 6.8 Hz, 4H), 3.01 (s, 12H), 1.71- 1.63 (m, 4H), 1.43-1.37 (m, 8H), 0.58-0.54 (m, 4H), 0.09-0.05 (m, 58H). Example 2.7 - Preparation of AB43311 O O

[0293] To a solution of (E)-3-(4-hydroxy-3,5-dimethoxyphenyl)acrylic acid (1, 10.0 g, 44.60 mmol, 1.0 eq) in THF (150 mL) were added pent-4-en-1-ol (1a, 15.37 g, 178.40 mmol, 4.0 eq) and DIAD (11.72 g, 57.98 mmol, 1.3 eq ) at RT. Then to the solution was added PPh3 (15.21 g, 57.98 mmol, 1.3 eq) slowly while stirring at 0oC. The reaction mixture was stirred for 16 h under N2 at RT. The reaction solution was quenched with water (150 mL) and filtered directly. The filtrate was extracted with DCM (150 mL * 3). The combined organic layers were washed with brine (150 mL), dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 5 / 1) and followed by reversed phase column (H2O / MeCN = 35 / 65) to afford compound 2 (8.24 g, 63%) as yellow oil. TLC: PE / EA = 5 / 1Rf (Compound 2) = 0.2 LC-MS: 293.2 [M+1]+1H NMR (400 MHz, Chloroform-d) δ 7.57 (d, J = 16.0 Hz, 1H), 6.75 (s, 2H), 6.29 (d, J = 16.0 Hz, 1H), 5.80 (d, J = 12.4 Hz, 2H), 5.11 – 4.94 (m, 2H), 4.20 (t, J = 6.0 Hz, 2H), 3.90 (s, 6H), 2.19-2.14 (m, 2H), 1.83-1.76 (m, 2H). Procedure for the Preparation of AB43311

[0294] To a solution of pent-4-en-1-yl (E)-3-(4-hydroxy-3,5- dimethoxyphenyl)acrylate (2, 5.38 g, 18.34 mmol, 2.0 eq) in toluene (55 mL) were added DMS-H05 (5.98 g, 9.17 mmol, 1.0 eq) and H2PtCl6·6H2O (237.47 mg, 0.46 mmol, 0.05 eq) at RT. The reaction mixture was stirred for 15 h under N2at 80oC. The reaction solution was filtered with celite directly. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 1 / 1) to afford AB43311 (7.24 g, 64%) as yellow oil.1H NMR (400 MHz, Chloroform-d) δ 7.58 (d, J = 16.0 Hz, 2H), 6.76 (s, 4H), 6.29 (d, J = 16.0 Hz, 2H), 5.77 (s, 2H), 4.18 (t, J = 6.8 Hz, 4H), 3.90 (s, 12H), 1.75 – 1.58 (m, 6H), 1.36 (d, J = 7.2 Hz, 10H), 0.55 (dd, J = 100, 5.9 Hz, 5H), 0.06 (s, 70H). Example 2.8 - Preparation of AB43317 O OH OH O 2

[0295] To a solution of 2-(4-(diethylamino)-2-hydroxybenzoyl)benzoic acid (2, 10.0 g, 31.9 mmol, 1.0 eq) in DMF (20 mL) were added compound 1 (8.6.g, 14.3 mmol, 0.45 eq), HOBt (9.0 g, 64 mmol, 2.0 eq), EDCI (12.0 g, 64 mmol, 2.0 eq) and TEA (16.0 g, 160 mmol, 5.0 eq), the mixture was stirred at 40 ℃ for 12 hours under N2 atmosphere. The reaction mixture was poured into water (200 mL), and then extracted with DCM (300 mL x 3). The organic phase was washed with brine (300 mL), dried overanhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography (PE / EA = 30 / 1 to DCM / MeOH = 20 / 1) to give AB43317 (10.2 g, 27%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 7.6, 2H), 7.60-7.48 (m, 4H), 7.34 (d, J = 7.6, 2H), 6.88 (d, J = 9.2 Hz, 2H), 6.12 (d, J = 2.4 Hz, 2H), 6.02 (d, J = 9.2, 2H), 4.27 (t, J = 5.2 Hz, 4H), 3.64 – 3.51 (m, 48H), 3.36 (q, J = 7.2 Hz, 8H), 1.16 (t, J = 7.2 Hz, 12H). Example 2.9 - Preparation of AB43318 NEt

[0296] To a solution of (E)-3-(3,4-dihydroxyphenyl) acrylic acid (1, 0.70 g, 3.88 mmol, 1.0 eq) in DMF (10 mL) were added compound 2 (4.27 g, 4.27 mmol, 1.1 eq), EDCI (1.5 g, 7.82 mmol, 2.0 eq), HOBt (1.05 g, 7.78 mmol, 2.0 eq) and TEA (1.2 g, 11.85 mmol, 3.0 eq), the reaction mixture was stirred at 45 ℃ for 12 hours under N2 atmosphere. The reaction mixture was added to water (50 mL), and then extracted with DCM (100 mL x 3), the organic phase was washed with brine (300 mL), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by RP-flash column chromatography (0.1% FA) to give compound 3 (0.8 g, 18%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.82 - 7.79 (m, 2H), 7.72 - 7.66 (m, 2H), 3.61 (s, 88H). Procedure for the Preparation of AB43318

[0297] To a solution of compound 3 (0.75 g, 0.65 mmol, 1.0 eq) and 2-(4- (diethylamino)-2-hydroxybenzoyl)benzoic acid (4, 150.0 g, 0.48 mol, 1.4 eq) in DMF (10 mL) were added HOBt (353 mg, 2.61 mmol, 4.0 eq), EDCI (238 mg, 1.24 mmol, 2.0 eq) and TEA (330 mg, 3.26 mmol, 5.0 eq), the reaction mixture was stirred at 45 ℃ for 12hours under N2 atmosphere. The1H NMR spectrum of crude showed the starting material was gone and the desired compound was generated. The residue was purified by RP-flash column chromatography (0.1% FA) to give AB43318 (0.45 g, 48%) as yellow oil.1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.0, 1H), 7.82 (d, J = 6.0, 2H), 7.69 (d, J = 5.6, 2H), 7.56 - 7.52 (m, 3H), 7.33 (d, J = 8.0, 1H), 6.87 (d, J = 9.2 Hz, 1H), 6.11 (s, 1H), 6.04 - 6.00 (m, 1H), 4.26 (t, J = 5.2 Hz, 2H), 3.87 (s, 2H), 3.65 - 3.53 (m, 83H), 3.35 (d, J = 7.2 Hz, 4H), 1.16 (t, J=8.0 Hz, 6H). Example 2.10 - Preparation of AB43320 O O

[0298] To a solution of compound 1 (20.0 g, 0.11 mol, 1.0 eq) in THF (200 mL) were added compound 1a (28.0 g, 0.33 mol, 3.0 eq), EDCI (25.5 g, 0.13 mol, 1.2 eq) and DMAP (1.35 g, 11.1 mmol, 0.1 eq) at RT. The reaction was stirred for 16 h under N2 at RT. The reaction solution was quenched with water (200 mL) and filtered directly. The filter cake was continuously rinsed with DCM until the filter cake turned white. The filtrate was extracted with DCM (200 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na2SO4and filtered. The filtrate wasconcentrated under reduced pressure and purified by flash column chromatography (PE / EA = 6 / 1) to afford compound 2 (12.5 g, 46%) as white solid. TLC: DCM / MeOH = 20 / 1 Rf (Compound 1) = 0.2 Rf(Compound 2) = 0.4 LC-MS: 247 [M+1]+1H NMR (400 MHz, Chloroform-d) δ 7.58 (d, J = 16.0 Hz, 1H), 7.10 (s, 1H), 7.00 (d, J = 8.4, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.26 (d, J = 16.0 Hz, 1H), 6.12 (s, 1H), 5.96 (s, 1H), 4.31 (t, J = 6.4 Hz, 2H), 2.34 (td, J = 7.2, 2.4 Hz, 2H), 1.98 (t, J = 2.4 Hz, 1H), 1.93 (p, J = 6.8 Hz, 2H). Procedure for the Preparation of AB43320

[0299] To a solution of compoud 2 (12.5 g, 50.7 mmol, 1.0 eq) in toluene (120 mL) were added DMS-H05 (33.2 g, 50.7 mmol, 1.0 eq), Pt catalyst (3.9 g, 10.1 mmol, 0.2 eq) and BHT (1.1 g, 5.07 mmol, 0.1 eq) at RT. The reaction was stirred for 16 h under N2 at 90oC. The reaction was detected by HPLC. The reaction solution was filtered with celite directly. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 4 / 1) to afford AB43320 (5.02 g, 8.6%) as white solid.1H NMR (400 MHz, Chloroform-d) δ 7.57 (d, J = 16.0 Hz, 2H), 7.09 (s, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 6.27-6.20 (m, 2H), 6.14-6.07 (m, 2H), 5.71 – 5.44 (m, 2H), 4.20 (t, J = 6.0 Hz, 4H), 2.27-2.18 (m, 4H), 1.85 (d, J = 8.0 Hz, 4H), 0.28 – 0.00 (m, 51H). Example 2.11 - Preparation of AB43321To a solution of DHB (10.0 g, 31.92 mmol, 1.0 eq) in DMF (100 mL) were added compound 1 (10.41 g, 14.36 mmol, 0.45 eq), EDCl (12.24 g, 63.82 mmol, 2.0 eq), HOBT (8.62 g, 63.82 mmol, 2.0 eq) and TEA (16.15 g, 159.57 mmol, 5.0 eq) was stirred for 16 h under N2 at 45oC. The reaction mixture was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 3 / 1) to afford AB43321 (7.1 g, 24%) as yellow oil. TLC: PE / EA = 3 / 1 Rf (Compound 1) = 0.1 Rf (AB43321) = 0.751H NMR (399 MHz, Chloroform-d) δ 12.59 (s, 2H), 8.07-8.02 (m, 2H), 7.58 (d, J = 1.6 Hz, 2H), 7.51 (d, J = 1.6 Hz, 2H), 7.37-7.32 (m, 2H), 6.88 (d, J = 9.2 Hz, 2H), 6.12 (d, J = 2.4 Hz, 2H), 6.02 (dd, J = 9.2, 2.4 Hz, 2H), 4.07 (d, J = 7.2 Hz, 4H), 3.34 (t, J = 7.2 Hz, 9H), 1.59-1.45 (m, 4H), 1.17 (t, J = 7.2 Hz, 13H), 0.49-0.37 (m, 4H), 0.12-0.05 (m, 56H). Example 2.12 - Preparation of AB43322O OH OH O NEt

[0300] To a solution of DHB (15.0 g, 47.9 mmol, 1.0 eq) in DMF (100 mL) were added compound 1 (20.9 g, 24.4 mmol, 0.5 eq), EDCl (18.4 g, 96 mmol, 2.0 eq), HOBT (12.9 g, 96 mmol, 2.0 eq) and TEA (24.2 g, 0.24 mol, 5.0 eq) was stirred for 16 h under N2 at 45oC. The reaction mixture was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 3 / 1) to afford AB43322 (9.1 g, 27%) as yellow oil. TLC: PE / EA = 5 / 1 Rf(Compound 1) = 0.7 Rf(AB43322) = 0.21H NMR (399 MHz, Chloroform-d) δ 12.63 (s, 1H), 7.80-7.73 (m, 2H), 7.48 (s, 4H), 7.30 (s, 2H), 6.91 (d, J = 9.2 Hz, 2H), 6.41 (s, 1H), 6.11-6.00 (m, 4H), 3.36 (q, J = 7.2 Hz, 8H), 3.24 (q, J = 7.2 Hz, 4H), 1.46-1.36 (m, 4H), 1.17 (t, J = 7.2 Hz, 12H), 0.88 (s, 1H), 0.49-0.41 (m, 3H), 0.10-0.03 (m, 51H). Example 2.13 - Preparation of AB43333 Procedure for the Preparation of Compound 2N N To a solution g, 0.97 mol,1.0 eq) in were g, , DCC (242.0 g, 1.17 mmol, 1.2 eq) and DMAP (12.0 g, 97 mmol, 0.1 eq), the reaction mixture was stirred at 25 ℃ for 16 hours under N2 atmosphere. The reaction mixture was added into water (1.5 L), and then extracted with DCM (1.2 L x 3), the organic phase was washed with brine (1 L), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography (PE / EA = 30 / 1 to 20 / 1) to give compound 2 (380.0 g, 89%) as yellow oil. TLC: PE / EA = 10 / 1 Rf (Compound 1) = 0.1 Rf (Compound 2) = 0.5 LC-MS: 438.7 [M+1]+1H NMR (400 MHz, CDCl3) δ 12.58 (s, 1H), 8.06 (dd, J = 7.6, 1.6 Hz, 1H), 7.59 (td, J = 7.6, 1.6 Hz, 1H), 7.52 (td, J = 7.6, 1.6 Hz, 1H), 7.35 (dd, J = 7.6, 1.6 Hz, 1H), 6.89 (d, J = 9.2 Hz, 1H), 6.16 (d, J = 2.4 Hz, 1H), 6.09 (d, J = 9.2 Hz, 1H), 5.76 – 5.63 (m, 1H), 4.98 – 4.87 (m, 2H), 4.13 (t, J = 6.4 Hz, 2H), 3.33 – 3.23 (m, 4H), 2.01-1.93 (m, 2H), 1.58 (dt, J = 16.4, 7.6 Hz, 6H), 1.32 (q, J = 7.6 Hz, 4H), 0.93 (t, J = 7.6 Hz, 6H). Procedure for the Preparation of AB43333 N N N DMS-H05 To a(2, 500.0 g, 1.14 mol, 1.3 eq) in toluene (4 L) were added DMS-H05 (570.0 g, 0.87 mol, 1.0 eq) and H2PtCl6.6H2O (22.8 g, 53.42 mmol, 0.05 eq), the reaction mixture was stirred at 90 ℃ for 16 hours under N2 atmosphere. The mixture was concentrated under reducedpressure to give a residue. The residue was purified by silica gel column chromatography (PE / EA = 30 / 1 to DCM) to give AB43333 (644.0 g, 49%) as yellow oil.1H NMR (400 MHz, CDCl3) δ 12.60 (s, 2H), 8.05 (dd, J = 8.0, 1.6 Hz, 2H), 7.60-7.55 (m, 2H), 7.50 (dt, J = 7.6, 1.6 Hz, 2H), 7.35 (d, J = 7.6 Hz, 2H), 6.87 (dd, J = 9.2, 3.2 Hz, 2H), 6.10 (d, J = 2.4 Hz, 2H), 6.01 (dt, J = 9.2, 2.4 Hz, 2H), 4.11 (t, J = 6.4 Hz, 4H), 3.27 (t, J = 8.0 Hz, 8H), 1.55 (q, J = 7.6 Hz, 12H), 1.37-1.15 (m, 16H), 0.93 (t, J = 7.2 Hz, 12H), 0.81 (s, 1H), 0.49 (s, 3H), 0.13-0.03 (m, 70H). Example 2.14 - Preparation of AB43334

[0301] To a solution of 4-(Dimethylamino)cinnamic acid (1, 30.0 g, 156.88 mmol, 1.0 eq) in Pyridine (300 mL) were added pent-4-en-1-ol (1a, 33.78 g, 0.39 mol, 2.5 eq) and EDCl (48.12 mg, 0.25 mol, 0.1 eq). The reaction mixture was stirred for 16 h under N2 at 45oC. After completion, the mixture was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 10 / 1) to afford AB43334 (19.0 g, 47%) as yellow soild. TLC: PE / EA = 5 / 1 Rf (Compound 1) = 0 Rf (Compound 2) = 0.6 LC-MS: 260.3 [M+H]+1H NMR (400 MHz, Chloroform-d) δ 7.62 (d, J = 16.0 Hz, 1H), 7.46-7.39 (m, 2H), 6.71- 6.63 (m, 2H), 6.23 (d, J = 16.0 Hz, 1H), 5.90-5.75 (m, 1H), 5.20-4.90 (m, 2H), 4.17 (t, J = 6.8 Hz, 2H), 3.02 (s, 6H), 2.25-2.10 (m, 2H), 1.90-1.75 (m, 2H). Example 2.15 - Preparation of AB43336Proc

[0302] To a solution of 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4- one (1, 25.0 g, 82.72 mmol, 1.0 eq) in DMF (250 mL) were added 1-iodohexane (2a, 70.17 g, 0.33 mol, 4.0 eq) and K2CO3 (45.73 g, 0.33 mol, 4.0 eq) at room temperature. The reaction mixture was stirred for 16 h under N2 at 80 °C. The reaction solution was quenched with water (600 mL) and filtered directly. The filtrate was extracted with EA (250 mL * 3). The combined organic layers were washed with brine (1 L), dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure to give a residue and the residue was purified by flash column chromatography (PE / EA = 50 / 1) to afford AB43336 (22.0 g, 48%) as yellow solid. TLC: PE / EA = 20 / 1 Rf (Compound 1) = 0 Rf (AB43336) = 0.7 LC-MS: 555.4 [M+1]+1H NMR (400 MHz, Chloroform-d) δ 12.69 (s, 1H), 7.71 (s, 2H), 6.95 (d, J = 8.4 Hz, 1H), 6.45 (d, J = 2.4 Hz, 1H), 6.35 (d, J = 2.4 Hz, 1H), 4.16 (t, J = 6.4 Hz, 2H), 4.03 (dt, J = 9.6, 6.4 Hz, 4H), 1.92-1.72 (m, 6H), 1.48-1.26 (m, 18H), 0.96-0.86 (m, 10H). Example 2.16 - Preparation of AB43337Procedure

[0303] To a solution of compound 1 (30.0 g, 99.3 mmol, 1.0 eq) in DMF (300 mL) were added compound 2a (105.3 g, 0.50 mol, 5.0 eq) and K2CO3 (68.6 g, 0.50 mol, 5.0 eq) at room temperature. The reaction mixture was stirred for 16 h under N2at 80 °C. The reaction solution was quenched with water (300 mL) and filtered directly. The filtrate was extracted with EA (400 mL * 3). The combined organic layers were washed with brine (300 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under reduced pressure to give a residue and the residue was purified by flash column chromatography (PE / EA = 100 / 1) to afford AB43337 (28.8 g, 45%) as yellow solid. TLC: PE / EA = 20 / 1 Rf(Compound 1) = 0 Rf (AB43337) = 0.91H NMR (400 MHz, Chloroform-d) δ 12.72 (s, 1H), 7.74-7.67 (m, 2H), 6.98 (d, J = 8.4 Hz, 1H), 6.44 (d, J = 2.4 Hz, 1H), 6.35 (d, J = 2.4 Hz, 1H), 4.05 (dq, J = 31.6, 6.8 Hz, 8H), 1.92-1.69 (m, 8H), 1.57-1.45 (m, 6H), 1.42-1.24 (m, 18H), 0.98-0.86 (m, 12H). Example 2.17 - Preparation of AB43338Procedure for the Preparation of AB43338

[0304] To a solution of (E)-3-(4-hydroxy-3,5-dimethoxyphenyl)acrylic acid (1, 10.0 g, 44.60 mmol, 1.0 eq) in THF (150 mL) were added pent-4-en-1-ol (1a, 15.37 g, 178.40 mmol, 4.0 eq) and DIAD (11.72 g, 57.98 mmol, 1.3 eq) at RT. Then to the solution was added PPh3 (15.21 g, 57.98 mmol, 1.3 eq) slowly while stirring at 0oC. The reaction mixture was stirred for 16 h under N2 at RT. The reaction solution was quenched with water (150 mL) and filtered directly. The filtrate was extracted with DCM (150 mL * 3). The combined organic layers were washed with brine (150 mL), dried over Na2SO4and filtered. The filtrate was concentrated under reduced pressure and purified by flash column chromatography (PE / EA = 5 / 1) and followed by reversed phase column (H2O / MeCN = 35 / 65) to afford AB43338 (8.24 g, 63%) as yellow oil. TLC: PE / EA = 5 / 1 Rf (AB43338) = 0.2 LC-MS: 293.2 [M+1]+1H NMR (399 MHz, Chloroform-d) δ 7.57 (d, J = 16.0 Hz, 1H), 6.75 (s, 2H), 6.29 (d, J = 16.0 Hz, 1H), 5.75-5.85 (m, 2H), 5.11-4.94 (m, 2H), 4.20 (t, J = 6.4 Hz, 2H), 3.90 (s, 6H), 2.17 (q, J = 6.8 Hz, 2H), 1.79 (p, J = 6.8 Hz, 2H). Example 2.18 - Preparation of AB43339

[0305] To a solution of compound 1 (20.0 g, 66.2 mmol, 1.0 eq) in Ac2O (50 mL, 2.5 V) was added Mg (79.5 mg, 3.31mmoL, 0.05 eq) at room temperature. The reaction mixture was stirred for 3 h under N2 at 50 °C. The reaction solution was quenched with water (300 mL) and filtered directly. The filtrate was extracted with EA (400 mL * 3). The combined organic layers were washed with brine (300 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under reduced pressure to give aresidue and the residue was purified by flash column chromatography (PE / EA = 10 / 1) to afford AB43339 (25.0 g, 80%) as yellow solid. TLC: PE / EA = 20 / 1 Rf (Compound 1) = 0 Rf(AB43339) = 0.7 1H NMR (400 MHz, Chloroform-d) δ 12.08 (d, J = 1.2 Hz, 1H), 7.75-7.70 (m, 2H), 7.38- 7.33 (m, 1H), 6.83 (dd, J = 2.0, 1.2 Hz, 1H), 6.58 (dd, J = 2.0, 1.2 Hz, 1H), 2.35 (d, J = 1.2 Hz, 3H), 2.32 (q, J = 1.2 Hz, 9H). Example 2.19 - Preparation of AB43340

[0306] To a solution of compound 2 (15.0 g, 31.89 mmol, 1.0 eq) in THF (150 mL) were added compound 2a (13.7 g, 159.4 mmol, 5.0 eq) and PPh3 (10.0 g, 38.13 mmol, 1.2 eq) at room temperature, then DIAD (7.73 g, 38.23 mmol, 1.2 eq) was added at 0oC. The reaction mixture was stirred for 16 h under N2 at RT. The reaction solution was quenched with water (300 mL) and filtered directly. The filtrate was extracted with EA (400 mL * 3). The combined organic layers were washed with brine (300 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under reduced pressure to give a residue and the residue was purified by flash column chromatography (PE / EA = 2 / 1) to afford AB43340 (8.0 g, 47%) as brown solid. TLC: PE / EA = 1 / 1 Rf (Compound 1) = 0.9 Rf (AB43340) = 0.5 LC-MS: 539 [M+1]+1H 1H NMR (400 MHz, Chloroform-d) δ 7.74 (d, J = 2.0 Hz, 1H), 7.73-7.68 (m, 4H), 7.66 (d, J = 2.0 Hz, 1H), 7.33 (d, J = 8.4 Hz, 3H), 6.90 (d, J = 2.0 Hz, 2H), 6.80 (d, J = 2.4 Hz, 1H), 6.62 (d, J = 2.4 Hz, 1H), 6.55 (d, J = 2.0 Hz, 2H), 5.84 (s, 3H), 5.10-4.97 (m, 6H), 4.15-4.02 (m, 9H), 2.35 (s, 6H), 2.34-2.28 (m, 36H), 2.02 (s, 6H). Example 2.20 - Preparation of AB43341

[0307] To a solution of 2-(4-(dibutylamino)-2-hydroxybenzoyl)benzoic acid (1, 360.0 g, 0.97 mol, 1.0 eq) in DCM (3 L) were added compound 1a (92.5 g, 1.07 mol, 1.1 eq), DCC (242.0 g, 1.17 mmol, 1.2 eq) and DMAP (12.0 g, 0.097 mol, 0.1 eq), the reaction mixture was stirred at 25 ℃ for 12 hours under N2 atmosphere. The reaction mixture was added into water (1.5 L), and then extracted with DCM (1.2 L x 3), the organic phase was washed with brine (1 L), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography (PE / EA = 30 / 1 to 20 / 1) to give AB43341 (380.0 g, 89%) as yellow oil. TLC: PE / EA = 10 / 1 Rf (Compound 1) = 0.1 Rf (AB43341) = 0.5 LC-MS: 438.7 [M+1]+1H NMR (400 MHz, CDCl3) δ 12.58 (s, 1H), 8.06 (dd, J = 7.6, 1.6 Hz, 1H), 7.59 (dt, J = 7.6, 1.6 Hz, 1H), 7.52 (dt, J = 7.6, 1.6 Hz, 1H), 7.35 (dd, J = 7.6, 1.6 Hz, 1H), 6.89 (d, J = 9.2 Hz, 1H), 6.16 (d, J = 2.4 Hz, 1H), 6.09 (d, J = 9.2 Hz, 1H), 5.76-5.63 (m, 1H),4.98-4.87 (m, 2H), 4.13 (t, J = 6.4 Hz, 2H), 3.33-3.23 (m, 4H), 2.01-1.93 (m, 2H), 1.58 (dt, J = 16.4, 7.6 Hz, 6H), 1.32 (q, J = 7.6 Hz, 4H), 0.93 (t, J = 7.2 Hz, 6H). Example 2.21 - Preparation of AB38403 3 OOHHO O O OH OOH O5OProcedure for the Preparation of Compound 4

[0308] To a suspension of compound 2 (350.0 g, 1.11 mol, 1.0 eq), compound 3 (105.8 g, 1.23 mol, 1.1 eq) and DMAP (13.6 g, 0.11 mmol, 0.1 eq) in DCM (5 L) under N2 atmosphere was added DCC (253.5 g, 1.23 mol, 1.2 eq), the resulting suspension was stirred at room temperature for 3 h. HPLC analysis indicated the amount of compound 2 is＜2%. The reaction was quenched with water (700 mL), filtered. The filter cake was washed with DCM (1 L). The filtrate was collected and separated, and the aqueous layer was extracted with dichloromethane (300 mL). The combined organic phases were concentrated in vacuo to afford a crude, which was purified by flash column chromatography (PE: EtOAc, 40:1) to afford compound 4 (345.1 g, 80%) as yellow oil. TLC: PE / EtOAc = 15 / 1 Rf (Compound 2) = 0.1 Rf (Compound 4) = 0.4Procedure for the Preparation of AB38403

[0309] To a suspension of DMS-H05 (400.0 g, 0.61 mol,1.0 eq) and compound 4 (310.6, 0.81 mol, 1.3 eq) in toluene (4 L) under N2 atmosphere was added H2PtCl6.6H2O (15.8 g, 30.5 mmol, 0.05 eq). The resulting mixture was heated at 90 ^C for 3 h. TLC (PE / EtOAc = 10 / 1) and1H NMR analysis indicated compound 4 was completely consumed. The mixture was filtered through a pad of Celite and purified by flash column chromatography (DCM, 100%) to afford compound #16 (AB38403, 530.0 g, 61%) as yellow oil. TLC: PE / EtOAc = 10 / 1 Rf (Compound 5) = 0.6 Rf (AB38403) = 0 1H NMR (400 MHz, CDCl3) δ 12.61 (d, J = 8.0 Hz, 2H), 8.05 (d, J = 8.0 Hz, 2H), 7.60 – 7.56 (m, 2H), 7.53 – 7.56 (m, 2H), 7.35 (d, J = 8.0 Hz, 2H), 6.90 – 6.87 (m, 2H), 6.14 (d, J = 4.0 Hz, 2H), 6.04 (dd, J = 8.0, 4.0 Hz, 2H), 4.12 (t, J = 8.0 Hz, 4H), 3.38 (q, 8H), 1.57 – 1.46 (m, 5H), 1.29 – 1.24 (m, 6H), 1.18 (t, J = 8.0 Hz, 13H), 0.82 (t, J = 8.0 Hz, 2H), 0.51 – 0.47 (m, 3H), 0.13 – 0.03 (m, 67H). Example 2.22 - Preparation of AB38314O O O Br O 10% NaOH aq. Br + h CHCl ,rt, overnight BrProcedure for the Preparation of Compound 3 O OMW:176.26 MW:308.3812 3

[0310] To a stirred solution of compound 1 (500.0 g, 2.83 mol, 1.0 eq) in ethanol (10 L) at room temperature was added 4-formylbenzoic acid (2, 426.0 g, 2.83 mol, 1.0 eq) and 10% NaOH aqueous (250 g NaOH dissolved in 2.5 L H2O). The resulting mixture was stirred at room temperature for 8 h. TLC (DCM / MeOH=20 / 1) and HPLC showed the reaction was completed. The solid formed was collected by filtration, and tothe solid was added dropwise 1 M hydrochloric acid to adjust pH=2~3. After filtration, the solid was re-crystallized with ethanol (15 L, 30 V) and washed with ice-water (500 mL) to give compound 3 (369.0 g, 42%) as a yellow solid. TLC: DCM / MeOH = 20 / 1 Rf (Compound 1) = 0.7 Rf(Compound 3) = 0.5 LC-MS: 309.4 [M+1]+1H NMR (400 MHz, DMSO-d6) δ 13.10 (s, 1H), 8.11 – 8.04 (m, 2H), 7.97 (d, J = 5.1 Hz, 5H), 7.58 – 7.53 (m, 2H), 1.29 (d, J = 1.6 Hz, 10H). Procedure for the Preparation of Compound 4 O O Br Br2To a L) aot 0 C was added dropwise Br2 (330.0 g, 2.06 mol, 1.7 eq) in CHCl3 (2.5 L). After addition, the mixture was stirred at room temperature overnight. To the mixture was added water (4 L) and extracted with DCM (3 L×3), dried and concentrated to afford compound 4 (516 g crude, 90%) as yellow solid. LC-MS: 469 [M+1]+, 467[M-1] -1H NMR (400 MHz, DMSO-d6) δ 8.23 – 8.16 (m, 2H), 7.95 (dd, J = 7.4, 5.7 Hz, 4H), 7.62 (dd, J = 8.6, 1.8 Hz, 2H), 6.66 (d, J = 11.3 Hz, 1H), 5.81 (d, J = 11.3 Hz, 1H), 1.30 (d, J = 1.5 Hz, 9H). Procedure for the Preparation of Compound 5 O Br O OH 1) NaOMe, MeOH, reflux, 2 h To aadded dropwise a solution of NaOMe (145.0 g, 2.67 mol, 5.0 eq) in methanol (1.2 L). Afteraddition, the mixture was heated to reflux and stirred for 1 h. Concentrated hydrochloric acid (300 mL) was added dropwise and the solution was allowed to reflux for an additional 1 h, then water (100 mL) was added and the solution was allowed to cool to room temperature. Filtration of the resulting precipitate to afford compound 5 (140.0 g, 80%) as white crystal. LC-MS: 325 [M+1]+1H NMR (400 MHz, DMSO-d6) δ 8.27 – 8.19 (m, 2H), 8.08 (dd, J = 14.5, 8.3, 1.6 Hz, 4H), 7.57 (dd, J = 8.7, 2.1 Hz, 2H), 7.35 (d, J = 1.9 Hz, 1H), 1.30 (d, J = 1.9 Hz, 9H). Procedure for the Preparation of Compound 7 6 O O O OH OH Owas added DCC (91.0 g, 0.44mol, 1.1eq) and DMAP (4.9 g, 40.1 mmol, 0.1 eq). The resulting mixture was cooled to 0oC, and then added dropwise a solution of pent-4-en- 1-ol (6, 41.4 g, 0.48 mol, 1.2 eq) in DCM (200 mL) under N2 atmosphere. After addition, the reaction mixture was stirred at room temperature for 2 h. The reaction was quenched with water, filtered and the filter cake was washed with DCM (600 mL×3), dried in vacuum to afford crude, which was purified by silica gel chromatography (PE: EtOAc=50:1) to afford compound 7 (125.0 g, 79%) as light red solid. LCMS: 393 [M+1]+1H NMR (400 MHz, Chloroform-d) δ 8.16–8.10 (m, 2H), 8.0 –8.00 (m, 2H), 7.96–7.90 (m, 2H), 7.56–7.48 (m, 2H), 6.86 (s, 1H), 5.85 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.12– 4.99 (m, 2H), 4.37 (t, J = 6.6 Hz, 2H), 2.23 (tdd, J = 7.9, 6.1, 1.4 Hz, 2H), 1.90 (dq, J = 8.4, 6.6 Hz, 2H), 1.35 (s, 9H), 0.07 (s, 1H). Procedure for the Preparation of AB38314O O O O HMS-H271g, was added H2PtCl6.6H2O (440 mg, 0.85 mmol, 0.05 eq). The resulting mixture was heated at 90 ^C for 4 h. TLC and HNMR analysis indicated compound 7 completely consumed. The mixture was filtered through celite and purified by flash column chromatography (DCM, 100%) to afford AB38314 (57.0 g) as black solid. TLC: PE / EA = 15 / 1 Rf (Compound 7) = 0.5 Rf(AB38314) = 0.4 1H NMR (399 MHz, Chloroform-d) δ 8.12–7.72 (m, 24H), 7.48 (s, 8H), 6.85 (d, J = 5.5 Hz, 4H), 4.29 (d, J = 14.1 Hz, 8H), 3.48–3.44 (m, 5H), 1.76 (s, 8H), 1.44 (s, 15H), 1.26 (d, J = 13.7 Hz, 36H), 0.55 (s, 8H), 0.07 (d, J = 9.7 Hz, 128H). Example 2.23 - Preparation of AB38315 Procedure for the Preparation of Compound 2 MgBr NH

[0313] To a2.25 mol, 1.0 eq) in THF (3 L) at 0oC was added phenylmagnesium bromide (2.25 L, 2.25 mol, 1.0 eq). The reaction was stirred at 55~60 ^C for 15 h. LC-MS indicated compound 1 completely consumed. The reaction was quenched with water (3L), filtered through Celite. The filterwas collected and extracted with EtOAc (100 mLx3), dried over anhydrous Na2SO4 and concentrated to afford compound 2 (467.0 g, 98%) as yellow oil. TLC: PE / EA = 10 / 1 Rf (Compound 1) = 0.8 Rf (Compound 2) = 0.2 LC-MS: 213.10 [M+1]+Procedure for the Preparation of Compound 3 Oand ethyl 2- cyanoacetate (493.0 g, 4.36 mol, 2.0 eq) in toluene (2.3 L) was heated at 105 ^C for 1 h and the mixture turned to a yellow transparent solution. LCMS indicated about 20% of compound 2 remained. The mixture was heated at 105 ^C for additional 3 h. After cooled to room temperature, water (2.3 L) was added, and the aqueous layer was extracted with EtOAc (1 L x 3). The combined organic phase was dried over sodium sulfate and concentrated in vacuo to afford compound 3 (900.0 g, crude) as brownish red oil. TLC: PE / EA = 10 / 1 Rf (Compound 2) = 0.2 Rf (compound 3) = 0.6 LC-MS: 308.10 [M+1]+Procedure for the Preparation of Compound 4

[0315] To a suspension of compound 3 (900.0 g, 2.92 mol, 1.0 eq) in methanol (2 L) and water (2 L) was added sodium hydroxide (234.0 g, 5.86 mol, 2.0 eq) at 0 ^C. The resulting mixture was heated at 40 ^C for 2 h. LCMS analysis indicated compound 3 completely consumed. After removal of methanol in vacuo, the aqueous phase was washed with MTBE, acidified with 1N HCl to adjust pH<3 and extracted with EtOAc (2 L x 3). The combined organic phase was washed with brine and water, dried over sodium sulfate and concentrated in vacuo to afford compound 4 (378.0 g, 46%) as yellow solid. TLC: PE / EA = 2 / 1 Rf (Compound 3) = 0.9 Rf (Compound 4) = 0.1 LC-MS: 280.05 [M+1]+Procedure for the Preparation of Compound 5 OH NC O (CH2)3NC O

[0316] bromoundec- 1-ene (362.7 g, 2.43 mol, 2.0 eq) and potassium carbonate (501.7 g, 3.63 mol,3.0 eq) in MeCN (3.4 L) was heated at 80 ^C for 15 h. HPLC analysis indicated compound 4 <2%. After filtration, the filtrate was concentrated and the residue was diluted with EtOAc (3.4 L) and H2O (1 L). After separation, the organic layer was dried over sodium sulfate and concentrated in vacuo to afford crude, which was purified by flash column chromatography (ethyl acetate in hexane, 0-100%) to afford compound 5 (276.0 g, 63%) as yellow oil. TLC: PE / EA = 5 / 1 Rf (Compound 4) = 0.1 Rf (Compound 5) = 0.6 LC-MS: 348.10 [M+1]+Procedure for the Preparation of AB38315NC O (CH ) O O g, 80.5mg, 0.89 mmol, 0.05 eq). The resulting mixture was heated at 90 ^C for 3 h. TLC and HNMR analysis indicated compound 5 completely consumed. The mixture was filtered through celite and purified by flash column chromatography (DCM, 100%) to afford AB38315 (62.7 g) as dark green oil. TLC: PE / EA = 10 / 1 Rf (Compound 5) = 0.6 Rf (Product AB38315) = 0 1H NMR (400 MHz, Chloroform-d) δ 7.49 – 7.38 (s, 20H), 7.15 – 7.08 (m, 8H), 6.92 – 6.85 (m, 8H), 4.12 (s, 4H), 4.04 (s, 4H), 3.85 – 3.83 (d, J = 6.8 Hz, 12H), 3.52 – 3.49 (d, J = 16.2 Hz, 8H), 1.58 – 1.47 (m, 10H), 1.29 – 1.26 (m, 20H), 0.49 (s, 8H), 0.13 – 0.07 (m, 132H). Example 2.24 - Preparation of AB38316

[0317] See Compound 7 procedure from AB38314 procedure. Procedure for the Preparation of compound 5A:

[0318] See Compound 5 procedure from AB38315 procedure. Procedure for the Preparation of AB38316

[0319] To a suspension of compound 7 (13.16 g, 33.56 mmol, 2.5 eq), 5A (11.65 g, 33.56 mmol, 2.5 eq), HMS-H271 (30 g, 13.42 mmol, 1.0 eq) in toluene (1.2 L) under N2 atmosphere was added H2PtCl6.6H2O (347.6 mg, 0.67 mmol, 0.05 eq), the resulting suspension was stirred at 85 °C for 5 h. TLC (PE:EtOAc=10:1) indicated the reaction was complete. After filtration, the filtrate was concentrated in vacuo to afford a yellow oil, which was evaporated to dryness and swapped with methanol to remove residual toluene, and then swapped with DCM to remove residual toluene and methanol. The residue was concentrated in vacuo several times to afford AB38316 (54 g) as dark green solid. TLC: PE / EA = 10 / 1 Rf (Compound 7) = 0.7 Rf (Compound 5A) = 0.5 Rf (AB38316) = 0.11H NMR (400 MHz, Chloroform-d) δ 8.12 – 7.92 (m, 14H), 7.52 – 7.37 (m, 15H), 7.13 – 7.07 (m, 5H), 7.07 – 6.86 (m, 7H), 4.32 (s, 5H), 4.10 – 4.03 (d, J = 28.0 Hz, 6H), 3.83 (d, J = 8.0 Hz, 8H), 3.47 (d, J =8.0 Hz, 13H), 1.77 (s, 5H), 1.46 (s, 10H), 1.35 – 1.25 (m, 30H), 0.54 – 0.48 (m, 10H), 0.08 – 0.06 (m, 124H). Example 2.25 - Preparation of AB38317O O O Br O 10% NaOH aq. Br + t-BuCOOHEtOH, r.t., 8 h CHCl ,rt, overnight t-BuCOOH90% t-Bu Br COOH

[0320] See Compounds 3-7 procedures from AB38314 procedure. Procedure for the Preparation of AB38317 HO O O Si O Si O Si O To57.37 mmol, 1.0 eq) in toluene (450 mL) under N2 atmosphere was added H2PtCl6.6H2O (1.2 g, 2.86 mmol, 0.05 eq), the resulting suspension was stirred at 90 °C for 6 h. After filtration, the filtrate was concentrated in vacuo to afford a yellow oil, which was triturated with methanol (300 mL) at -10oC for 1 h. After filtration, the solid was dried under reduced pressure to obtain AB38317 (55.0 g, 87%) as white waxy solid. TLC: PE / EA = 15 / 1 Rf (Compound 7) = 0.5 Rf (AB38317) = 0.41H NMR (400 MHz, Chloroform-d) δ 8.12 (d, J = 1.5 Hz, 4H), 8.02 (d, J = 8.1 Hz, 4H), 7.93 (d, J = 8.4 Hz, 4H), 7.51 (d, J = 8.4 Hz, 4H), 6.86 (s, 2H), 4.36 – 4.32 (m, 4H), 3.48 (s, 1H), 1.81 – 1.77 (m, 4H), 1.51 – 1.39 (m, 8H), 1.36 (d, J = 0.7 Hz, 18H), 0.60 – 0.56 (m, 4H), 0.10 – 0.04 (m, 62H). Example 2.26 - Preparation of AB38318 O OH MgBr NH O NC NC O NC O CN O NaOH O SiProcedure for the Preparation of Compounds 2-5:

[0321] See Compound 2-5 procedures from AB38315 procedure. Procedure for the Preparation of AB38318 O Si 7

[0322] and DMS- H05 (50 g, 76.52 mmol, 1.0 eq) in toluene (500 mL) was added H2PtCl6.6H2O (1.63 g, 3.8mmol, 0.05 eq). The resulting mixture was heated to 90 ^C for 3 h. TLC and HNMR analysis indicated compound 5 completely consumed. The mixture was filtered through Celite and concentrated in vacuo to afford crude AB38318. The crude was dissolved in methanol and stirring for 20 min, then cooled down to -50°C to precipitate and remove,the product was concentrated in vacuo to afford crude product, which was purified by flash column chromatography (DCM, 100%) to afford AB38318 (67.5 g, 65%) as yellow oil. TLC: PE / EA = 10 / 1 Rf(Compound 5) = 0.6 Rf(Product AB38318) = 0 1H NMR (399 MHz, Chloroform-d) δ 7.51 – 7.32 (m, 10H), 7.16 – 7.07 (m, 4H), 6.94 – 6.83 (m, 4H), 4.08 (dtd, J = 31.3, 6.7, 3.0 Hz, 4H), 3.87 – 3.80 (m, 6H), 1.52 – 1.38 (m, 4H), 1.35 – 1.17 (m, 10H), 0.48 (s, 4H), 0.12 – 0.01 (m, 67H). Example 2.27 - Preparation of AB38120 Cl O OHOClO NC NC NC HO (CHMW:249.27

[0323] To a solution of ethyl 2-cyano-3,3-diphenylacrylate (1, 100.0 g, 0.36 mol, 1.0 eq) in ethanol (1 L) was added NaOH (31.7 g, 0.79 mol, 2.2 eq) in H2O (150 mL). The reaction was stirred at room temperature for 18 h. The reaction solution was concentrated in vacuo to afford a yellow solid. To the solid was added water, washed with MTBT and acidified with 1 N hydrochloric acid to adjust pH=2~3. After being stirredfor 30 minutes, the solid was collected by filtration, and dried to afford compound 2 (72.0 g, 80%) as white solid. TLC: PE / EA = 5 / 1 Rf (Compound 1) = 0.6 Rf (Compound 2) = 0.31H NMR (400 MHz, DMSO-d6) δ 13.69 (s, 0H), 7.51–7.40 (m, 4H), 7.40–7.31 (m, 5H), 7.18–7.06 (m, 2H). Procedure for the Preparation of Compound 3 Cl OHOClNC O NC

[0324] To a solution of compound 2 (30.0 g, 0.12 mol, 1.0 eq) and DMF (three drops) in DCM (300 mL) at 0 °C was added oxalyl dichloride (51 mL, 0.6 mol, 5.0 eq) dropwise. After addition, the mixture was stirred at room temperature for 30 minutes, and concentrated in vacuo to afford compound 3 (33.0 g, crude) as yellow solid. TLC: PE / EA = 5 / 1 Rf (Compound 1) = 0.6 Rf (Compound 2 ) = 0.3 Procedure for the Preparation of Compound 4 Cl NC HO (CH2)9NC O (CH2)9

[0325] To a solution of undec-10-en-1-ol (18.4 g, 0.108 mol, 0.9 eq), TEA (12.1 g, 0.12 mol, 1.0 eq) in toluene (230 mL) under N2 atmosphere at 0oC was added dropwise a solution of compound 3 (33.0 g, 0.12 mol, 1.0 eq) in DCM (230 mL). After addition, the mixture was stirred at room temperature for 1 h. After reaction completed, water was added, extracted with DCM three times and concentrated to obtain crude product, whichwas purified by flash column chromatography (PE / EA=15:1) to afford compound 4 (32.0 g, 66%) as yellow oil. TLC: PE / EA = 10 / 1 Rf (Compound 3) = 0.2 Rf (Compound 4 ) = 0.71H NMR (400 MHz, DMSO-d6) δ 7.57–7.30 (m, 8H), 7.16–7.08 (m, 2H), 5.01–4.85 (m, 2H), 3.96 (t, J = 6.4 Hz, 2H), 2.00–1.91 (m, 2H), 1.35–0.94 (m, 15H). Procedure for the Preparation of AB38120 Si S)11GP-6781O i O Si(CH2H2)1 (COeq), GP-678 (61.9 g, 31.13 mmol, 1.0 eq) and H2PtCl6.6H2O (806 mg, 1.56 mmol, 0.05 eq) in toluene (125 mL). Replacing the air in the kettle with N2 atmosphere and maintaining the pressure at 0.1MPa, the resulting suspension was stirred at 90 °C for 16 h. After filtration, the filtrate was concentrated in vacuo to afford a black oil, which was triturated with methanol (50 mL x 3) for 1 h. After pouring out methanol, the crude residue (~70 g) was absorbed onto silica gel (200 g) and purified by flash column chromatography (DCM, 100%) to afford AB38120 (67.0 g, 77%) as colorless oil. TLC: PE / EA = 15 / 1 Rf(Compound 4) = 0.5 Rf (AB38120) = 0.41H NMR (400 MHz, CDCl3) δ 7.51–7.33 (m, 16H), 4.07 (t, J = 6.7 Hz, 4H), 1.48 (p, J = 6.9 Hz, 10H), 1.26 (d, J = 23.3 Hz, 36H), 0.52 (t, J = 7.4 Hz, 5H), 0.06 (s, 179H). Example 2.28 - Preparation of AB38121in THF (1 L) at 0oC was added phenylmagnesium bromide (750 mL, 0.75 mol, 1.0 eq). The reaction was stirred at 55~60 ^C for 15 h. LC-MS indicated compound 1 completely consumed. The reaction was quenched with water, filtered through a pad of Celite. The filtrate was collected and extracted with EA, dried over anhydrous Na2SO4 and concentrated to afford compound 2 (140.0 g, 88%) as yellow oil. TLC: PE / EA = 10 / 1 Rf (Compound 1) = 0.8 Rf (Compound 2) = 0.2 LC-MS: 212.05 [M+1]+Procedure for the Preparation of Compound 3

[0328] A suspension of (4-methoxyphenyl)(phenyl)methanimine (2, 140.0 g, 0.66 mol, 1.0 eq) and ethyl 2-cyanoacetate (373.0 g, 3.3 mol, 5.0 eq) in toluene (1.4 L) was heated at 105 ^C for 1 h and the mixture turned to a yellow solution. LCMS indicated about 20% of compound 2 remained. The mixture was heated at 105 ^C for additional 3 h. After being cooled to room temperature, water (1.4 L) was added; and the aqueous layer was extracted with EA (400 mL x 3). The combined organic phase was dried over sodium sulfate and concentrated in vacuo to afford compound 3 (494.0 g, crude) as brownish red oil. TLC: PE / EA = 10 / 1 Rf (Compound 2) = 0.2 Rf (compound 3) = 0.6 LC-MS: 308.10 [M+1]+Procedure for the Preparation of Compound 4-3- phenylacrylate (3, 490.0 g, 1.59 mmol, 1.0 eq) in methanol (1 L) and water (80 mL) was added sodium hydroxide (127.5 g, 3.18 mol, 2.0 eq) at 0 ^C. The resulting mixture was heated to 40 ^C for 2 h. LCMS analysis indicated compound 4 completely consumed. After removal of methanol in vacuo, the aqueous phase was washed with MTBE, acidified with 1N HCl to pH <3 and extracted with EA (1 L x 3). The combined organic phase was washed with brine and water, dried over sodium sulfate and concentrated in vacuo to afford a crude, which was triturated with PE / EA (10 / 1, v / v) and dried to afford compound 4 (146 g, 32%) as yellow solid. TLC: PE / EA = 2 / 1 Rf (Compound 3) = 0.9 Rf (Compound 4) = 0.1 LC-MS: 280.05 [M+1]+Procedure for the Preparation of Compound 5 OH NC NC O (CH2) O9Br (CH2)9

[0330] acid (4,70.0 g, 0.25 , ene g, eq) and cesium carbonate (245 g, 0.75 mol,3.0 eq) in acetonitrile (700 mL) was heated at 80 ^C for 15 h. LCMS analysis indicated compound 4 completely consumed. The mixture was diluted with water (100 mL), extracted with ethyl acetate (2x 500 mL), dried over sodium sulfate and concentrated in vacuo to afford a crude product, which was purified by flash column chromatography (ethyl acetate in hexane, 0-100%) to afford compound 5 (43.0 g, 40%) as yellow oil. TLC: PE / EA = 5 / 1 Rf (Compound 4) = 0.1 Rf (Compound 5) = 0.6 LC-MS: 454.20 [M+23]+Procedure for the Preparation of AB38121 2)11O Oeq), GP-678 (51.5 g, 25.478 mmol, 1.0 eq) and H2PtCl6.6H2O (660 mg, 1.274mmol, 0.05 eq) in toluene (200 mL). Replacing the air in the reactor with N2 atmosphere and maintaining the pressure at 0.1MPa, the resulting suspension was stirred at 90 °C for 16 h. After filtrating through a pad of Celite, the filtrate was concentrated in vacuo toafford a black oil, which was triturated with methanol (50 mL x 2). After pouring out methanol, the crude residue (~46 g) was obtained. Several batches of crude product (~104.5 g) were combined and purified by flash column chromatography (DCM, 100%) to afford AB38121 (103.0 g, 59%) as colorless oil. TLC: PE / EA = 10 / 1 Rf(Compound 5) = 0.5 Rf (Product AB38121) = 0.41H NMR (400 MHz, CDCl3) δ 7.41–7.36 (m, 10H), 7.15–7.08 (m, 4H), 6.92–6.85 (m, 4H), 4.14–4.11 (m, 2H), 4.06–4.03 (m, 2H), 3.84 (s, 3H), 3.83 (s, 3H), 1.56–1.45 (m, 4H), 1.29- 1.24 (m, 34H), 0.52 (t, J = 8.0 Hz, 5H), 0.09-0.03 (m, 200H). Example 2.29 - Preparation of AB38122 O O O Br +ONaOH Br H CHCl ,rt, overnight BrProcedure for the Preparation of Compound 3 O O

[0332] To a stirred solution of compound 1 (126.9 g, 0.72 mol, 1.0 eq) in ethanol (2 L) at room temperature was added 4-formylbenzoic acid (2, 108.1 g, 0.72 mol, 1.0 eq) and NaOH / H2O (1 / 10, v / v) (540 mL). The resulting mixture was stirred at room temperature for 8 h. TLC (DCM / MeOH=20 / 1) and HPLC showed the reaction was completed. To the solution was added dropwise 1 M hydrochloric acid to pH 2~3. After filtration, the solid was dried and recrystallized from ethanol and dried to give compound 3 (97.0 g, 44%) as a yellow solid. TLC: DCM / MeOH = 20 / 1 Rf (Compound 1) = 0.7 Rf (Compound 3) = 0.5 LC-MS: 309.4 [M+1]+1H NMR (400 MHz, DMSO-d6) δ 13.10 (s, 1H), 8.11 – 8.04 (m, 2H), 7.97 (d, J = 5.1 Hz, 5H), 7.58 – 7.53 (m, 2H), 1.29 (d, J = 1.6 Hz, 10H). Procedure for the Preparation of Compound 4 O O Br Br2

[0333] in chloroform (3 L) at 0oC was added dropwise bromine (85.0 g, 0.54 mol, 1.7 eq) in chloroform (1 L). After the addition, the mixture was stirred at room temperature overnight. Water (1 L) was added, extracted three times with DCM (2 x 1L). The combined organic layers were washed with water and brine, dried over sodium sulfate and concentrated to afford compound 4 (crude 144.0 g, 96 %) as yellow solid. LC-MS: 469 [M+1]+ / 467[M-1]+1H NMR (400 MHz, DMSO-d6) δ 8.23 – 8.16 (m, 2H), 7.95 (dd, J = 7.4, 5.7 Hz, 4H), 7.62 (dd, J = 8.6, 1.8 Hz, 2H), 6.66 (d, J = 11.3 Hz, 1H), 5.81 (d, J = 11.3 Hz, 1H), 1.30 (d, J = 1.5 Hz, 9H). Procedure for the Preparation of AB38210O Br O OH 1) NaOMe, MeOH, reflux, 2 h Br 2) HCl, reflux, 1 hadded dropwise a solution of sodium methoxide (78.3 g, 1.45 mol, 5.0 eq) in methanol (400 mL). After the addition, the mixture was heated to reflux and stirred for 2 h and cooled to room temperature. Concentrated hydrochloric acid (150 mL) was added dropwise and the solution was allowed to reflux for an additional 1 h. Water (500 mL) was added and the solution was allowed to cool to room temperature. Filtration of the resulting precipitate and drying in vacuo afforded AB38210 (72.3 g, 76%) as white crystal. LC-MS: 325 [M+1]+1H NMR (400 MHz, DMSO-d6) δ 8.27 – 8.19 (m, 2H), 8.08 (dd, J = 14.5, 8.3, 1.6 Hz, 4H), 7.57 (dd, J = 8.7, 2.1 Hz, 2H), 7.35 (d, J = 1.9 Hz, 1H), 1.30 (d, J = 1.9 Hz, 9H). Procedure for the Preparation of Compound 7 6 O O O OH HO (CH2)9O

[0335] in DCM (400 mL) was added DCC (15.36 g, 74.0 mmol 1.0eq) and DMAP (0.9 g, 7.4 mmol, 0.1 eq). The resulting mixture was cooled to 0oC, and then a solution of undec-10-en-1-ol (6, 25.2 g, 0.144 mol 2.0 eq) in DCM (100 mL) was added dropwise under N2 atmosphere. After the addition, the reaction mixture was stirred at room temperature for 2 h. The reaction was filtered and the filter cake was washed with DCM. The filtrate was dried in vacuo to afford a crude, which was purified by silica gel chromatography (PE: EtOAc=50:1) to afford compound 7 (23.1 g 65%) as light red solid. LCMS: 477 [M+1]+1H NMR (400 MHz, DMSO-d6) δ 8.23 (d, J = 8.1 Hz, 1H), 8.06 (dd, J = 12.3, 8.1 Hz, 2H), 7.55 (d, J = 8.2 Hz, 1H), 4.98 – 4.84 (m, 1H), 4.26 (t, J = 6.6 Hz, 1H), 1.95 (q, J = 7.2 Hz, 1H), 1.68 (p, J = 6.7 Hz, 1H), 1.34 (d, J = 7.4 Hz, 1H), 1.25 (d, J = 27.1 Hz, 10H).Procedure for the Preparation of g,, mg, mL) in an autoclave under N2 atmosphere maintaining the pressure at 0.1 MPa was stirred at 90 °C for 16 h. After filtration through a pad of Celite, the filtrate was concentrated in vacuo to afford an oil, which was triturated with methanol. The crude residue (~55 g) was absorbed onto silica gel (50 g) and purified with flash column chromatography (DCM, 100%) to afford AB38122 (40.0 g, 65%) as red solid. TLC: PE / EA = 15 / 1 Rf (Compound 7) = 0.5 Rf (AB38122 ) = 0.41H NMR (400 MHz, CDCl3) δ 16.82 (s, 2H), 8.15–8.13 (m, 4H), 8.03–8.01 (m, 4H), 7.95– 7.93 (m, 4H), 7.52–7.50 (m, 4H), 6.87 (s, 2H), 4.36–4.33 (m, 4H), 3.47 (s, 1H), 1.80–1.77 (m, 4H), 1.45–1.27 (m, 42H), 0.54–0.51 (m, 4H), 0.10–0.06 (m, 154H).Example 3 – Evaluation of Polymeric ROS Agents

[0337] Polymeric ROS agents prepared in accordance with the schemes described above, were evaluated for their ROS inhibition and ROS capture capacities, as well as their E11 and maximum absorbance, in accordance with the assay methods described elsewhere herein.Results are given in Table 3.1 below: PolymerROS inhibition Measured(RNO) ROS capturexampe – n a u y on mpac o apurers on oosa y

[0338] Formulations containing AB38317 at 12 wt% and 20 wt%, each containing 1 wt% quercetin were prepared as follows.

[0339] KB004-19: In a glass beaker, an oil phase was prepared using 16.7% caprylic / capric triglyceride, 5.2% C12-C15 alkyl benzoate, 2.3% phenylethyl benzoate and heated to 65oC while mixing. To the oil phase, following ingredients were added while heating: 12% AB38317, 1% quercetin, 1% poly C10-30 alkyl acrylate, 1.6% glyceryl stearate, 1.3% PEG-100 stearate, 0.5% cetearyl alcohol, 0.7% sodium stearoyl glutamate and 5.5 % SunSphere powder (containing 90% styrene / acrylate copolymer). In another glass beaker, water phase was prepared containing water (q.s.), 3% glycerin, 0.05% disodium ethylenediaminetetraacetic acid, 0.07% acrylates / C10-30 alkyl acrylate crosspolymer and 0.2% xanthan gum and heated to 65oC. Once the oil and water phase reached the set temperatures, oil phase was added to water phase while mixing and homogenized at 12,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer. The emulsion was allowed to cool below 50oC and then 0.3% phenoxyethanol, 0.3% caprylyl glycol and 1% sodium acrylate / acryloyldimethyltaurate / dimethylacrylamide crosspolymer were added. Finally mass balance was performed to replace evaporated water, and allowed to further mix for a minimum of 15 minutes at room temperature. The final water content of the formulation was 47.3%.

[0340] KB004-33: In a glass beaker, an oil phase was prepared using 8.7% caprylic / capric triglyceride, 5.2% C12-C15 alkyl benzoate, 2.3% phenylethyl benzoate and heated to 65oC while mixing. To the oil phase, following ingredients were added while heating: 20% AB38317, 1% quercetin, 1% poly C10-30 alkyl acrylate, 1.6% glyceryl stearate, 1.3% PEG-100 stearate, 0.5% cetearyl alcohol, 0.7% sodium stearoyl glutamate and 5.5 % SunSphere powder (containing 90% styrene / acrylate copolymer). In another glass beaker, water phase was prepared containing water (q.s.), 3% glycerin, 0.05% disodium ethylenediaminetetraacetic acid, 0.07% acrylates / C10-30 alkyl acrylate crosspolymer and 0.2% xanthan gum and heated to 65oC. Once the oil and water phase reached the set temperatures, oil phase was added to water phase while mixing and homogenized at 12,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer. The emulsion was allowed to cool below 50oC and then 0.3% phenoxyethanol, 0.3% caprylyl glycol and 1% sodium acrylate / acryloyldimethyltaurate / dimethylacrylamide crosspolymer were added. Finally mass balance was performed to replace evaporatedwater, and allowed to further mix for a minimum of 15 minutes at room temperature. The final water content of the formulation was 47.3%.

[0341] The formulations were evaluated by in vitro absorbance testing in accordance with Example 1. The absorbance characteristics are shown in Table 4.1. The change in absorbance during photostability testing of KB004-19 at 0, 15, 30, 45, and 60 minutes of solar simulator irradiation is shown in Table 4.1 and that of KB004-33 at 0, 30, and 60 minutes is shown in Table 4.2.

[0342] The increased concentration of AB38317 in these formulations resulted in a lower initial %UVA-T (higher initial absorbance) Table 4.1 – KB004-19 Absorbance Photostability Characteristics Sample UV Irradiation Timepoint In vitro %UVA-T In vitro UVA-PF KB004-19 0 39 62Table 4.2 – KB004-33 Absorbance Photostability Characteristics Sample UV Irradiation Timepoint In vitro %UVA-T In vitro UVA-PFExample 5 – Further Study of Impact of ROS Capturers

[0343] Formulations containing AB38403 at 20-24 wt% were prepared containing no, or various types and amounts of, flavonoids. As shown in Table 3.1. Such formulations were tested by the hybrid diffuse reflectance spectroscopy (HDRS) method, as described elsewhere herein, with a subject panel size of 6-7. For clarity, the %UVA-T determined and reported via the HDRS method is after UV irradiation (1.2 J / cm2capped at UVA-Pfinit of 30 (i.e. no more than 36 J / cm2 UVA)) and adjustment forphotostability (as described in ISO / DIS23698). The geometric mean (averaged across all participating panelists) %UVA-T determined via HDRS is shown in Table 5.1 below. Generally, an increase in (UVA absorbing) flavonoid leads to lower UVA transmission. Reduction of %UVA-T from about 3-4% to 1-3% by addition of small amounts (2-4 wt%) of certain flavonoids is surprising considering the extinction coefficient of the flavonoids and their low solubility. Table 5.1: HDRS Measurement of %UVA-T for Select Formulations Formulation Composition (weight %) Type HDRS HDRS UVA-PF HDRS AB38403LuteolinQuercetin %UVA-T (pre-irradiation) UVA-PF )O / W = oil-in-water formulation Example 6 - Further Study of Impact of ROS Capturers

[0344] Formulations containing various amounts of AB38403 and 3-4 wt% of UVA absorbing flavonoids were evaluated by the HDRS method using a panel size of 6- 7 subjects. The final %UVA-T determined by HDRS is shown, along with the spectral ratio of photodegradation minimum (SRPDmin), a measure of photostability. The viscosity of each formulation was measured using a TA Instruments Discovery HR30 rheometer with 40mm parallel plate geometry and 600 micron gap on a peltiercontrolled stage at 25°C by conducting a flow sweep of shear rate from 10-3to 103 / sec. The viscosity at 1 / sec is reported in x1000 cPs (kcPs). Increasing the concentration of PDMS-DHB results in an expected decrease of %UVA-T. However, surprisingly, varying the base ingredients and the corresponding formulation viscosity also had a significant impact on the %UVA-T. Table 6.1: Characteristics of Examples Composition (weight%) HDRS HDRS Viscosity HDRS UVA-PF UVA-PF )

[0345] KB006-87 and BK006-83 differed only by the amount of thickener and thus demonstrate the impact of viscosity alone. Example 7 – Antioxidant Staining Tests

[0346] Purple and blue light have wavelengths slightly greater than that of UVA radiation. Purple visible light is generally considered to have wavelengths of 380 to 450 nm and blue light 450-495 nm. Absorbance of purple and blue light result in the appearance of a yellow color. Chemical species with absorbance maxima in the UVA range (320 – 400 nm) typically have some residual absorbance (peak tail) into the visible (purple-blue) portion of the electromagnetic spectrum. As a result of absorbance of wavelengths longer than about 380 nm, even UVA absorbers can impart a yellow color. Many ingredients used in cosmetic and skincare formulations, both natural and synthetic, are insoluble in water, surfactant solutions, and also many organic solvents. In addition to their instability, these ingredients may also have a tendency to adhere to both natural and synthetic fibers used in textiles. These properties causeformulations containing such ingredients to adversely stain textiles such as clothing, towels, bed sheets, etc. In addition to the absorbance properties, and hence color, of ingredients, the chemical reactivity of such ingredients can also affect their absorbance properties and color. For example, ingredients such as flavonoids with ionizable groups may be protonated or deprotonated at low or high pH respectively, as the pH ranges found for simultaneously used cosmetic products, acid-containing cleaning solutions, alkaline soap solutions or alkaline bleach solutions. Similar color changes can occur as a result of metal chelation. A well-known property of many flavonoids is a strong yellow color at high pH (above 9).

[0347] To evaluate the staining of fabric, about 20 mg of formulation was applied by rubbing with finger into to a white cotton t-shirt. A digital photograph was recorded under white light conditions. The fabric was then washed under hot-wash laundry conditions with laundry detergent. A second digital photograph under white light conditions was recorded. The degree of staining is visually assessed and quantified using ImageJ plot profile function. Plot profile of a rectangular section about 300 pixels wide was used to calculate the gray value across the stain spot images taken before and after washing. The profile was baseline corrected based on the average value of unstained white fabric of the first and last 10 pixels and 10-period moving averages are plotted. The average gray value of the stain spots after baseline correction are shown in the table.

[0348] The commercially available reference product, UVMune400, was purchased and contained following combination of ingredients according to the product label: water, alcohol denat, triethyl citrate, diisopropyl sebacate, silica, ethylhexyl salicylate, bis-ethylhexyloxyphenol methoxyphenyl triazine, ethylhexyl triazone, butyl methoxydibenzoylmethane, glycerin, propanediol, C12-22 alkyl acrylate / hydroxyethylacrylate copolymer, methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate, perlite, tocopherol, caprylic / capric triglyceride, acrylates / C10- 30 alkyl acrylate crosspolymer, caprylyl glycol, diethylamino hydroxybenzoyl hexyl benzoate, drometrizole trisiloxane, hydroxyethylcellulose, terephthalylidene dicamphor sulfonic acid, triethanolamine, trisodium ethylenediamine disuccinate, fragrance.Test Formulation Number 1 2 3 4 UVMune400 Flavonoid content 0.1% luteolin 0.5% luteolin 4% luteolin, 4% luteolin NoneExample 8 - Preparation of Exemplary Composition of the Invention

[0349] Further exemplary compositions where prepared as follows.

[0350] KB004-42: In a glass beaker, an oil phase was prepared using 7.7% caprylic / capric triglyceride, 5.2% C12-C15 alkyl benzoate, 2.3% phenylethyl benzoate and heated to 75oC while mixing. To the oil phase, following ingredients were added while heating: 20% AB38403, 2% luteolin, 1% poly C10-30 alkyl acrylate, 1.6% glyceryl stearate, 1.3% PEG-100 stearate, 0.5% cetearyl alcohol, 0.7% sodium stearoyl glutamate and 5.5 % SunSphere powder (containing 90% styrene / acrylate copolymer). In another glass beaker, water phase was prepared containing water (q.s.), 3% glycerin, 0.05% disodium ethylenediaminetetraacetic acid, 0.07% acrylates / C10-30 alkyl acrylate crosspolymer and 0.2% xanthan gum and heated to 765oC. Once the oil and water phase reached the set temperatures, oil phase was added to water phase while mixing and homogenized at 12,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer. The emulsion was allowed to cool below 50oC and then 0.3% phenoxyethanol, 0.3% caprylyl glycol and 1% sodium acrylate / acryloyldimethyltaurate / dimethylacrylamide crosspolymer were added. Finally mass balance was performed to replace evaporated water and allowed to further mix for a minimum of 15 minutes at room temperature. The final water content of the formulation was 47.3%.

[0351] KB005-65: In a glass beaker, an oil phase was prepared using 2.0% Isodecyl Neopentanoate, 2.0% Isostearyl Neopentanoate, 1.3% Ethylhexyl Palmitate, 2% Cetyl PEG / PPG-10 / 1 Dimethicone, 1.4% Stearyl Dimethicone, 2% Caprylyl methicone, 24% AB38403, 0.26% tocopherol, 1.0% poly C10-30 alkyl acrylate, 0.8% PEG-100 Stearate, 1.2% glyceryl stearate, 0.34% cetearyl alcohol, 0.2% sodiumstearoyl glutamate, 1.0% vinyl dimethicone / methicone silsesquioxane crosspolymer and polymethylsilsesquioxane. The oil phase contents were heated to 80oC while mixing and once the set temperature was reached, heating was turned off and mixture was allowed to cool down at room temperature while mixing. Once the temperature was below 50oC, 3.7% cyclopentasiloxane, 0.7%, cyclopentasiloxane (and) dimethiconol, 0.7% dimethicone (and) dimethicone crosspolymer, 1% dimethicone (and) dimethicone / vinyl dimethicone crosspolymer, 0.7% dimethicone (and) dimethicone / vinyl dimethicone crosspolymer (and) dimethicone crosspolymer (and) beeswax (and) silica (and) silica Silylate, 1% Isododecane (and) dimethicone / bis-isobutyl PPG-20 crosspolymer, 1% caprylyl glycol (and) phenoxyethanol (and) hexylene glycol were added to the oil phase. In another glass beaker, water phase was prepared by adding water (q.s.), 0.05% disodium ethylenediaminetetraacetic acid, 29.4 % sunsphere PGL polymer, 3% aloe barbadensis 10x concentrated leaf juice, 0.1% luteolin, 0.5% calendula officinalis flower extract, and 2.25% Actiphyte green tea extract. Aqueous sodium hydroxide (10%) solution was used to adjust pH of the water phase to 6. Oil phase contents were added to water phase beaker while mixing to form emulsion and homogenized at 12,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer. Then, 0.7% hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer (and) polyisobutene (and) PEG-7 trimethylolpropane coconut ether and 0.1% fragrance were added to the emulsion. Finally mass balance was performed to replace evaporated water and allowed to further mix for a minimum of 15 minutes at room temperature. The final water content of the formulation was 41.1%.

[0352] KB006-47: In a glass beaker, an oil phase was prepared using 3.2% Isodecyl Neopentanoate, 1.4% Ethylhexyl Palmitate, 3.2% caprylic / capric triglyceride, 2.2% Cetyl PEG / PPG-10 / 1 Dimethicone, 2.7% Caprylyl methicone, 23.9% XG-3705, 1.0% poly C10-30 alkyl acrylate, 0.85% PEG-100 Stearate, 1.2% glyceryl stearate, 0.2% cetearyl alcohol, 0.2% sodium stearoyl glutamate, 0.7% vinyl dimethicone / methicone silsesquioxane crosspolymer and polymethylsilsesquioxane. The oil phase contents were heated to 75oC while mixing and once the set temperature was reached, heating was turned off and mixture was allowed to cool down at room temperature while mixing. Once the temperature was below 50 oC, 3% C9-C12 alkane, 3% triheptanoin (and) C13-16 isoalkane, 2.6% isododecane (and) dimethicone / bis-Isobutyl PPG-20 crosspolymer and 1% caprylyl glycol (and) phenoxyethanol (and) hexylene glycol were added to the oil phase. In another glass beaker, water phase was prepared by adding water (q.s.), 0.05% disodium ethylenediaminetetraacetic acid, 14.7 % sunsphere PGL polymer, 3% aloe barbadensis 10x concentrated leaf juice, 0.25% luteolin, 0.7% naringenin, 0.5% calendula officinalis flower extract, 0.76% pentylene glycol, and 2.25% Actiphyte green tea extract. Aqueous sodium hydroxide (10%) solution was used to adjust pH of the water phase to 6. Oil phase contents were added to water phase beaker while mixing to form emulsion and homogenized at 12,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer. Then, 0.2% of hyaluronic acid MW 800 - 1500 kDA, 0.2% hyaluronic acid MW 100 - 500 kDA and 0.2% hyaluronic acid MW 8 - 15 kDA were added and mixed to 15-30 minutes. Finally 0.5% hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer (and) polyisobutene (and) PEG-7 trimethylolpropane coconut ether and 0.1% was added to the emulsion, mass balance was performed to replace evaporated water and allowed to further mix for a minimum of 15 minutes at room temperature. The final water content of the formulation was 40.1%.

[0353] KB006-83: In a glass beaker, an oil phase was prepared using 3% Isostearyl neopentanoate, 1.4% ethylhexyl palmitate, 1.6% caprylic / capric triglyceride, 1.0% Cetyl PEG / PPG-10 / 1 Dimethicone, 2.3% caprylyl methicone, 23.9% XG-3705, 1.0% poly C10-30 alkyl acrylate, 0.8% PEG-100 Stearate, 1.8% glyceryl stearate, 0.5% cetearyl alcohol, 0.5% sodium stearoyl glutamate, 0.75% vinyl dimethicone / methicone silsesquioxane crosspolymer and polymethylsilsesquioxane. The oil phase contents were heated to 75oC while mixing and once the set temperature was reached, heating was turned off and mixture was allowed to cool down at room temperature while mixing. Once the temperature was below 50 oC, 3% C9-C12 alkane, 3% triheptanoin (and) C13-16 isoalkane, 2.6% isododecane (and) dimethicone / bis-Isobutyl PPG-20 crosspolymer and 1% caprylyl glycol (and) phenoxyethanol (and) hexylene glycol were added to the oil phase. In another glass beaker, water phase was prepared by adding water (q.s.), 0.05% disodium ethylenediaminetetraacetic acid, 14.7 % sunsphere PGL polymer, 4% luteolin, 0.74% pentylene glycol. Oil phase contents were added to water phase beaker while mixing to form emulsion and homogenized at 12,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer. Then, 0.2% of hyaluronic acid MW 800 - 1500 kDA, 0.2% hyaluronic acid MW 100 - 500 kDA and 0.2% hyaluronic acid MW 8 -15 kDA were added and mixed to 15-30 minutes. Finally, 0.5% hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer (and) polyisobutene (and) PEG-7 trimethylolpropane coconut ether was added to the emulsion, mass balance was performed to replace evaporated water and allowed to further mix for a minimum of 15 minutes at room temperature. Aqueous sodium hydroxide (10%) solution was used to adjust pH of the water phase to 6. The final water content of the formulation was 40.8%.

[0354] KB006-87: In a glass beaker, an oil phase was prepared using 3% Isostearyl neopentanoate, 1.5% ethylhexyl palmitate, 2.5% caprylic / capric triglyceride, 1.0% Cetyl PEG / PPG-10 / 1 Dimethicone, 2.3% caprylyl methicone, 24% XG-3705, 1.0% poly C10-30 alkyl acrylate, 1.2% PEG-100 Stearate, 1.8% glyceryl stearate, 0.5% cetearyl alcohol, and 0.5% sodium stearoyl glutamate. The oil phase contents were heated to 75oC while mixing and once the set temperature was reached, heating was turned off and mixture was allowed to cool down at room temperature while mixing. Once the temperature was below 50 oC, 3% C9-C12 alkane, 3% triheptanoin (and) C13-16 isoalkane, 2.6% isododecane (and) dimethicone / bis-Isobutyl PPG-20 crosspolymer and 1.1% caprylyl glycol (and) phenoxyethanol (and) hexylene glycol were added to the oil phase. In another glass beaker, water phase was prepared by adding water (q.s.), 0.05% disodium ethylenediaminetetraacetic acid, 14.7 % sunsphere PGL polymer, 4% luteolin, 0.77% pentylene glycol. Oil phase contents were added to water phase beaker while mixing to form emulsion and homogenized at 12,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer. Finally, 0.51% hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer (and) polyisobutene (and) PEG-7 trimethylolpropane coconut ether was added to the emulsion, mass balance was performed to replace evaporated water and allowed to further mix for a minimum of 15 minutes at room temperature. Aqueous citric acid (10%) solution was used to adjust pH of the water phase to 6. The final water content of the formulation was 40.7%.

[0355] KB007-03: In a glass beaker, an oil phase was prepared using 3.0% caprylic / capric triglyceride, 5.2% C12-C15 alkyl benzoate, 2.4% phenylethyl benzoate, 24% AB38403, 1% poly C10-30 alkyl acrylate, 1.6% glyceryl stearate, 1.3% PEG-100 stearate, 0.5% cetearyl alcohol, 0.7% sodium stearoyl glutamate and 4.2% SunSphere powder (containing 90% styrene / acrylate copolymer). The oil phase was heated to 75C while mixing. In another glass beaker, water phase was prepared containing water(q.s.), 3% glycerin, 0.05% disodium ethylenediaminetetraacetic acid, 0.07% acrylates / C10-30 alkyl acrylate crosspolymer and 0.2% xanthan gum and heated to 75oC. Once the oil and water phase reached the set temperatures, oil phase was added to water phase while mixing. Then 4% luteolin was added to the emulsion and homogenized at 12,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer. The emulsion was allowed to cool below 50oC and then 1% caprylyl glycol (and) phenoxyethanol (and) hexylene glycol and 1% of sodium acrylate / acryloyldimethyltaurate / dimethylacrylamide crosspolymer were added. Finally mass balance was performed to replace evaporated water, pH was adjusted to 6.0 using 10% citric acid solution, and further mixed for a minimum of 15 minutes at room temperature. The final water content of the formulation was 46.7%.

[0356] KB007-15: In a glass beaker, an oil phase was prepared using 4.0% caprylic / capric triglyceride, 5.2% C12-C15 alkyl benzoate, 2.4% phenylethyl benzoate, 24% AB38403-3, 1% poly C10-30 alkyl acrylate, 1.6% glyceryl stearate, 1.3% PEG-100 stearate, 0.5% cetearyl alcohol, 0.7% sodium stearoyl glutamate and 4.2% SunSphere powder (containing 90% styrene / acrylate copolymer). The oil phase was heated to 75C while mixing. In another glass beaker, water phase was prepared containing water (q.s.), 3% glycerin, 0.05% disodium ethylenediaminetetraacetic acid, 0.07% acrylates / C10-30 alkyl acrylate crosspolymer and 0.2% xanthan gum and heated to 75oC. Once the oil and water phase reached the set temperatures, oil phase was added to water phase while mixing. Then 2% luteolin and 1% quercetin were added to the emulsion and homogenized at 12,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer. The emulsion was allowed to cool below 50oC and then 0.5% caprylyl glycol, 0.5% phenoxyethanol and 1% sodium acrylate / acryloyldimethyltaurate / dimethylacrylamide crosspolymer were added. Finally mass balance was performed to replace evaporated water, pH was adjusted to 6.0 using 10% aqueous citric acid solution, and further mixed for a minimum of 15 minutes at room temperature. The final water content of the formulation was 46.8%.

[0357] KB008-17: In a glass beaker, add 15.8% isopropyl myristate, 20% AB38403-3, 3% lauryl PEG-10 tris(trimethylsiloxy)silylethyl dimethicone, 5% cetyl PEG / PPG-10 / 1 dimethicone, 4.2% SunSphere powder (containing 90% styrene / acrylate copolymer), 5% pentylene glycol, 4% luteolin, 1% quercetin, and 42.1% isododecane(and) dimethicone / bis-isobutyl PPG-20 crosspolymer while stirring. The mixture was homogenized at 15,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer.

[0358] KB008-25: In a glass beaker, add 15.8% isopropyl myristate, 12% AB38403-3, 3% lauryl PEG-10 tris(trimethylsiloxy)silylethyl dimethicone, 5% cetyl PEG / PPG-10 / 1 dimethicone, 4.2% SunSphere powder (containing 90% styrene / acrylate copolymer), 5% pentylene glycol, 4% luteolin, 1% quercetin, and 50.0% isododecane (and) dimethicone / bis-isobutyl PPG-20 crosspolymer while stirring. The mixture was homogenized at 15,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer.

[0359] KB008-27: In a glass beaker, add 15.8% isopropyl myristate, 16% AB38403-3, 3% lauryl PEG-10 tris(trimethylsiloxy)silylethyl dimethicone, 5% cetyl PEG / PPG-10 / 1 dimethicone, 4.2% SunSphere powder (containing 90% styrene / acrylate copolymer), 5% pentylene glycol, 4% luteolin, 1% quercetin, and 46.0% isododecane (and) dimethicone / bis-isobutyl PPG-20 crosspolymer while stirring. The mixture was homogenized at 15,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer.

[0360] KB010-01: In a glass beaker, added 5.1% isopropyl myristate, 7.5% hexyl laurate, 5.8% dicaprylyl carbonate, 5.8% isopropyl lauroyl sarcosinate, 24% AB38403-3, 3% lauryl PEG-10 tris(trimethylsiloxy)silylethyl dimethicone, 5% cetyl PEG / PPG-10 / 1 dimethicone, 5% pentylene glycol, 6% caprylic / capric triglyceride (and) stearalkonium hectorite (and) propylene carbonate, 2% stearic acid, and 1.5% glyceryl behenate. The contents were mixed and heated to 75C. While heating, 1% aluminum starch octenylsuccinate, 4.2% SunSphere powder (containing 90% styrene / acrylate copolymer), and 0.5% Silica dimethyl silylate were added to the beaker. Once the set temperature was reached, heat was turned off and mixture was allowed to cool at room temperature while mixing. Finally, 23.6% isododecane (and) dimethicone / bis-isobutyl PPG-20 crosspolymer was added below 50C and the mixture was homogenized at 15,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer.

[0361] KB010-11: In a glass beaker, added 6.6% hexyl laurate, 5.9% isopropyl lauroyl sarcosinate, 23.9% AB38403-3, 3% lauryl PEG-10 tris(trimethylsiloxy)silylethyl dimethicone, 5% cetyl PEG / PPG-10 / 1 dimethicone, 4.2% pentylene glycol, 6% caprylic / capric triglyceride (and) stearalkonium hectorite (and) propylene carbonate, 2% stearic acid, 2.0% glyceryl behenate, and 0.8% trihydroxystearin. The contents weremixed and heated to 80C. While heating, 1% aluminum starch octenylsuccinate, and 4.2% SunSphere powder (containing 90% styrene / acrylate copolymer) were added to the beaker. Once the set temperature was reached, heat was turned off and mixture was allowed to cool at room temperature while mixing. In the cooling phase, 0.11% narigenin, 0.5% luteolin, 0.05% apigenin, and 0.1% hesperidin were added to the mixture. Once the temperature was below 50C, 5.2% hexadecane, 4.9% dicaprylyl carbonate, and 23.4% isododecane (and) dimethicone / bis-isobutyl PPG-20 crosspolymer were added. Finally, 0.75% silica dimethyl silylate was added and the mixture was homogenized at 15,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer.

[0362] KB010-13: In a glass beaker, added 6.7% hexyl laurate, 5.8% isopropyl lauroyl sarcosinate, 24% AB38403-3, 3% lauryl PEG-10 tris(trimethylsiloxy)silylethyl dimethicone, 5% cetyl PEG / PPG-10 / 1 dimethicone, 4.2% pentylene glycol, 6% caprylic / capric triglyceride (and) stearalkonium hectorite (and) propylene carbonate, 2% stearic acid, 2.0% glyceryl behenate, and 0.8% trihydroxystearin. The contents were mixed and heated to 80C. While heating, 1% aluminum starch octenylsuccinate, and 4.2% SunSphere powder (containing 90% styrene / acrylate copolymer) were added to the beaker. Once the set temperature was reached, heat was turned off and mixture was allowed to cool at room temperature while mixing. In the cooling phase, 0.10% narigenin, 0.75% luteolin, 0.05% apigenin, and 0.1% hesperidin were added to the mixture. Once the temperature was below 50C, 5.5% hexadecane, 4.8% dicaprylyl carbonate, and 23.3% isododecane (and) dimethicone / bis-isobutyl PPG-20 crosspolymer were added. Finally, 0.75% silica dimethyl silylate was added and the mixture was homogenized at 15,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer.

[0363] KB010-15: In a glass beaker, added 6.6% hexyl laurate, 5.8% isopropyl lauroyl sarcosinate, 23.9% AB38403-3, 3% lauryl PEG-10 tris(trimethylsiloxy)silylethyl dimethicone, 5% cetyl PEG / PPG-10 / 1 dimethicone, 4.2% pentylene glycol, 6.1% caprylic / capric triglyceride (and) stearalkonium hectorite (and) propylene carbonate, 2.0% stearic acid, 2.0% glyceryl behenate, and 0.8% trihydroxystearin. The contents were mixed and heated to 80C. While heating, 1% aluminum starch octenylsuccinate, and 4.2% SunSphere powder (containing 90% styrene / acrylate copolymer) were addedto the beaker. Once the set temperature was reached, heat was turned off and mixture was allowed to cool at room temperature while mixing. In the cooling phase, 0.10% narigenin, 0.25% luteolin, 0.05% apigenin, and 0.1% hesperidin were added to the mixture. Once the temperature was below 50C, 6% hexadecane, 4.8% dicaprylyl carbonate, and 23.5% isododecane (and) dimethicone / bis-isobutyl PPG-20 crosspolymer were added. Finally, 0.75% silica dimethyl silylate was added and the mixture was homogenized at 15,000 rpm for 5 minutes using IKA T25 ultra turrax homogenizer.

[0364] To evaluate the staining of fabric, about 20 mg of formulation was applied by rubbing with finger into to a white cotton t-shirt, in triplicate. A digital photograph was recorded under white light conditions. The fabric was then washed under hot-wash laundry conditions with laundry detergent. A second digital photograph under white light conditions was recorded. The degree of staining is visually assessed and quantified using ImageJ plot profile function. Plot profile of a rectangular section across the stain location pixels wide was used to calculate the gray value of the background and stain, before and after washing. The profile was baseline corrected based on the average value of unstained white fabric of the first and last 10 pixels of each profile. The average and standard deviation of the gray value of the stain spots after baseline correction are shown in the table. Formulations containing flavonoids with absorbance max > 360 nm (quercetin and morin) showed the most intense staining prior to washing. However, following wash, all spots were comparable to baseline. This test represents a worst-case scenario as formulations are applied directly to white cotton in relatively large quantity.

[0365] The compositions of each of the sample formulations are summarized in the table below: Sample ID BEMT AB38403 AB38318 Naringeni Apigenin Luteolin Quercetin Rutin (%) Morin (%) Carote Type (%) (%) (%) n (%) (%) (%) (%) noid / xa nthone ol us us us us ous ous ous ous ous ol

[0367] Stain intensities are before and after washing, for each sample, are summarised in the table below and presented in Fig.1. stain, pre-wash stain, post-wash Sample Average Std Dev Sample Average St DevExample 9 – Emollient Compatibility Study

[0368] An emollient / solvent miscibility study was performed where AB38403 was mixed with various emollients / solvents used in skin care formulations at 1:1 ratio in 20 mL glass vials. The content of the vials was mixed for 5 seconds by vertexing. An initial observation of miscibility and appearance was recorded and then the vials were allowed to sit at room temperature for 72 hrs and observation of miscibility and appearance was recorded again.^Emollient / Solvent Initial observation Observation after 72 hours Phases miscible with clear Phases miscible with clearfor further formulation development.Example 10 – Usability of Skincare Compositions

[0370] One problem in the skincare industry is the challenge inherent in developing formulations that are both effective and pleasant to use. Consumers are more likely to use skincare products that offer a pleasant sensory experience. For many consumers, one important attribute of a desirable cosmetic feel for a skincare formulation is that it feels “lightweight” rather than “heavy.” Some other attributes of a desirable cosmetic feel for a skincare formulation are: pleasant and balanced visual appearance of the formulation itself; post-application appearance of skin that is neither too shiny nor too dry; easy spreadability, quick absorption, a pleasant skin feel upon application that is neither sticky nor greasy, a silky luxurious after-feel, and acceptable color or fragrance.

[0371] Anhydrous skincare formulations—formulations made without water as an ingredient—generally tend to feel more “lightweight” than oil-in-water or water-in-oil formulations. With an anhydrous formulation, it is also generally easier to achieve other aspects of a desirable cosmetic feel such as rich and luxurious texture, quick absorption, easy spreadability, and silky skin feel. Anhydrous formulations are formulated with significant levels of emollients and therefore, they also tend to leave the skin feeling well-hydrated and moisturized when applied. An additional benefit of anhydrous skincare formulations is that because they do not contain water, the formulations have a reduced risk of microbial growth and do not require addition of preservatives, making them particularly suitable for sensitive skin.

[0372] It is, however, difficult to make an anhydrous formulation that retains a desirable cosmetic feel while incorporating sufficient amounts of ingredients to make the formulation effective at, for example, protecting consumers from the harmful effects of ultraviolet radiation. In particular, incorporating a high amount of a single ingredient can lead to challenges such as phase separation, non-uniform distribution of active ingredients, poor suspension, and photoinstability as well as reduced efficacy. The inventors have surprisingly discovered compositions which successfully incorporate sufficient AB38403 in combination with naturally occurring flavonoids such as luteolin, apigenin, naringenin and hesperidin into an anhydrous formulation to achieve meaningful UVA absorption while preserving the attributes of a desirable cosmetic feel. Specifically, the inventors were able to incorporate 24wt% AB38403 along with theflavonoid combination into an anhydrous formulation while retaining the desirable cosmetic feel by carefully selecting a combination of emollients, feel enhancers, thickeners and oil gelling agents that are miscible / compatible with AB38403 and yield good spreadability, quick absorption, a pleasant after-feel that is neither tacky nor oily, and the appearance of a pleasant “glow” without appearing dry or shiny and without leaving a white cast even on darker skin. As a result of the invention, we are able to produce anhydrous formulations that not only possess all the critical daily wear cosmetics attributes such as pleasant appearance and texture, excellent spreadability, quick absorption, a non-greasy or sticky skin feel upon application, and a silky luxurious after-feel, but also have excellent suspension, photostability and UVA absorption efficacy.

[0373] An example of an anhydrous formulation that is widely considered to have a desirable cosmetic feel but fails to achieve its intended level of efficacy at protecting the wearer from ultraviolet radiation is Supergoop Unseen Sunscreen SPF 40. This formulation claims to provide an SPF of 40, but independent tests show that the formulation in fact only provides SPF of <24 and UVA-PF of <14.

[0374] An example of an oil-in-water formulation that provides effective protection against UVA ultraviolet radiation is KB006-83. When tested, this formulation achieved UVA-PF of 41, which is significantly better than most known sun-protective products. However, the cosmetic feel of this formulation is heavier than anhydrous formulations, and individuals of different skin types and colors also reported that it felt tacky and had a less desirable cosmetic feel than many consumers want.

[0375] An example of an anhydrous formulation that is likely to provide effective protection against UVA ultraviolet radiation but does not have a desirable cosmetic feel is KB008-89. In vitro data suggests that this formulation would likely achieve UVA-PF of 20-30 on HDRS testing, which would be significantly better than most known sun- protective products. However, the cosmetic feel of this formulation is poor.

[0376] An example of an anhydrous formulation that provides effective protection against UVA ultraviolet radiation and has a desirable cosmetic feel, is KB010-11. When tested, this formulation achieved UVA-PF of 40. Multiple individuals with varying skin colors and types agreed that this formulation feels good.ı66KB004-64 KB005-21 KB008-25 KB008-27 KB008-17 Antioxidant AB38403 (24.8%), 24% AB38403 AB38403 (12%), AB38403 (16%), AB38403 (20%), e ate s- 0 ne edAbsorption Quick absorption Quick absorption Quick absorption Quick absorption Quick absorption Cosmetic feel Overall good but can Overall good but can Overall good but can Overall good but Overall good but feel oily for certain feel oily for certain feel oily for certain can feel oily for can feel oily for e t ner d nAntiOx system AB38403 (24%) AB38403 (24%) AB38403 (24%) AB38403 (24%), AB38403 (24%), ), %) ), %) te, n, - with h e ut -2=Small oil layer on top upon storage n h -Example 11 – Evaluation of Polymeric ROS Agents

[0377] The performance of the polymeric ROS agents described herein as ROS inhibitors was evaluated in accordance with the following method.

[0378] Singlet oxygen formation (and potentially other radical species) were by loss of absorbance of p-nitrosodimethylaniline (RNO) in the presence of imidazole (IMD). IMD is used to convert singlet oxygen species into peroxide (IMD transannular peroxide intermediate), while RNO may also scavenge hydroxyl radicals directly (if present). Absorbance of 440 to 490 nm (which is characteristic of RNO) is reduced as nitrosodimethylaniline is converted to nitrodimethylaniline. Photogeneration of reactive oxygen species such as singlet oxygen may be accomplished with known photosensitizers, such as quinine, titanium dioxide particles (e.g. P25), or photoinitiators such as 4,4′-Bis(dimethylamino)benzophenone. Where only one photosensitizer is required, quinine (e.g., as quinine sulfate) can be selected. Exposure of the photosensitizer to UV radiation mimicking that of the solar spectrum (solar simulatorradiation) generates reactive oxygen species (ROS) such as singlet oxygen. Typical assay conditions include dissolution of Quinine, IMD, RNO at 200 µM, 10 mM, and 20 40 µM respectively in in 2033% DMSO and 8067% 10mM 25mM citrate or phosphate buffer at pH 7 or 7.4. Recommended stock solution preparation is as follows: RNO stock: 10 mM RNO in isopropanol; quinine sulfate stock: 1.6 mM quinine sulfate in water (equivalent to 3.2 mM quinine); 1M citrate in 20% DMSO pH 5: Dissolve citric acid in 20% DMSO / 80% water to about 1.25M. Adjust pH to 5 with sodium hydroxide, QS with 20% DMSO (aq) to a final concentration of 1M citrate. RNO 4x Stock: 40mM IMD, 160 µM RNO, 400 µM quinine sulfate (800 µM quinine), 100 mM citrate in 25% DMSO and 75% water, pH ~7 (for example, 54.5 mg IMD, 0.32 mL of 10mM RNO stock, 5 mL of 1.6mM quinine sulfate stock, 2 mL of 1M citrate in 20% DMSO pH 5, 4.6 mL DMSO, and 8.08 mL water for 20 mL total volume, final pH should be 7-8. If necessary adjust pH to 7-8); No-RNO 4x Stock: Same preparation as RNO 4x Stock in which the RNO stock volume is replaced with water. The compound(s) to be tested is( / are) added at a range of different concentrations (e.g., between 0.5 and 50200 µM). Specifically, antioxidant capturer (luteolin) is added in DMSO to final concentrations of 0, 0.6, 1.3, 2.5, 5, 10, 15, 20, 30, 40, and 50 µM. Separately, ROS inhibitor compounds are mixed to the same series of antioxidant capturer concentrations at either 2x or 4x concentration multiples (2:1 and 4:1 inhibitor to capturer). Finally, the ROS inhibitor compound is tested alone at concentrations of 0, 2.5, 5, 10, 20, 40, 60, 80, 120, 160, and 200 µM). Typically stock solutions of ROS capturer and inhibitor compounds are prepared at 10x concentration in DMSO. To prepare the assay plates, to each well of three standard 96 well plates (e.g. Costar UVStar cyclic olefin copolymer) 130 uL of 50% water / 50% DMSO solution is added. Then either 50 uL of RNO 4x stock or no- RNO 4x stock is added to all 96 wells of the plate (two plates with RNO 4x stock and one plate with no-RNO stock). The 10x concentrated ROS capturer and inhibitor mixtures are added, 20 µL per well in duplicate and the plates are mixed well. The sample One plate containing RNO stock and the plate containing no-RNO stock solutions (commonly in a multiwell plates (without lid or with UV-transparent lid) or sealed quartz cuvette, is are exposed to UV irradiation. The UV radiation source may be a solar simulator (e.g. Atlas CPS+), a UVA source, or a UVB source. Irradiation conditions should ensure that RNO absorbance of control experiments is almost or completely eliminated. Typical irradiation conditions using a solar simulator are about72.5 mW / cm2UV (250 W / m2300-800 nm) for 3020 minutes in a solar simulator (Atlas CPS+) with temperature controlled to about 30-40 °C. After UV exposure, about 30 volume % of alcohol (e.g. isopropanol) 100 µL of each sample well is mixed with 100 µL of DMSO is added to each sample volume, and the absorbance in the range of 440-490 nm (preferably 440 nm) is recorded (e.g. Varioskan Lux plate reader). The unirradiated RNO stock containing plate is similarly diluted with DMSO as an untreated control. The corresponding no-RNO sample well average absorbance is subtracted from both the unirradiated and irradiated RNO sample wells in order to correct for any absorbance or turbidity of the ROS inhibitor or capturer compounds. The ratio of corrected absorbance of the irradiated to unirradiated sample well averages are calculated. The amount of ROS inhibition owing to the test compound(s) are determined against controls containing only photosensitizer and RNO / IND. Hence, the concentration of test compound resulting in a 50% reduction in the loss of absorbance for a suitable wavelength in the range of 440-490 nm may be determined (i.e. the ROS inhibition IC50). IC50 values were determined by GraphPad Prism. Results of the experiments conducted are given in the table below.fold lower IC50 vs Solubility RNO Assay results Lut only challenging ID 2:1 4:1 * Cop, , uM. The concentration of ROS inhibitor (“inh”), that is, ID AB38403, etc., is 2 or 4x, (“inh:cap” = ROS inh : ROS cap) Example 12 – Exemplary Formulations

[0379] Exemplary formulations are described below. In the table below, “A” denotes avobenzone; “O” denotes octocrylene; “EHMC” denotes ethylhexylmethoxycrylene; “DHHB” denotes diethylamino hydroxybenzoyl hexyl benzoate; “BEMT” denotes bemotrizinol, and “SAC” denotes styrene acrylates copolymer.Boosters UV and / or Filters Pol meric ROS Luteoli Querceti SAC C C C C C C C+ 5% BEMT PK1-48 Anhydrou 10% 3.75% [0p p y p nce with the analytical methods described herein and are presented in Fig.2. Enumerated Embodiments 1. A composition comprising an antioxidant system, wherein the antioxidant system comprises ROS agents; wherein the composition has a %UVA-T of no more than 10%. 2. The composition of any preceding Embodiment, wherein the ROS agents comprise a polymeric ROS agent and, optionally, a free ROS agent. 3. The composition of any preceding Embodiment, wherein the ROS agents comprise a free ROS agent and, optionally, a polymeric ROS agent. 4. The composition of any preceding Embodiment, wherein the ROS agents comprise a free ROS agent and a polymeric ROS agent. 5. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 500 Da. 6. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 600 Da. 7. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 700 Da. 8. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 800 Da. 9. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 900 Da. 10. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 1000 Da.11. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 1500 Da. 12. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 2000 Da. 13. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 10000 Da. 14. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 20000 Da. 15. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 30000 Da. 16. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 40000 Da. 17. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 50000 Da. 18. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 9%. 19. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 8%. 20. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 7%. 21. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 6%. 22. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 5%. 23. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 4%. 24. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 3%.25. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 2%. 26. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 1%. 27. The composition of any preceding Embodiment, wherein the %UVA-T is measured by hybrid diffuse reflectance spectroscopy (HDRS), optionally measured as described elsewhere herein. 28. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 5%; and wherein the polymeric ROS agent has a molecular weight of at least 1000 Da. 29. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 15. 30. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 14. 31. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 13. 32. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 12. 33. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 11. 34. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 10. 35. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 9. 36. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 8. 37. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 7.38. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 6. 39. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 5. 40. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 4. 41. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 3. 42. The composition of any preceding Embodiment, wherein the composition has an SPF of less than 2. 43. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 5%; and wherein the polymeric ROS agent has a molecular weight of at least 1000 Da; and wherein the composition has an SPF of less than 15. 44. The composition of any preceding Embodiment, wherein the antioxidant system has an ROS inhibition IC50 of 100 mM or less, 45. The composition of any preceding Embodiment, wherein the antioxidant system has an ROS inhibition IC50 of 10mM or less. 46. The composition of any preceding Embodiment, wherein the antioxidant system has an ROS inhibition IC50 of 5mM or less. 47. The composition of any preceding Embodiment, wherein the antioxidant system has an ROS inhibition IC50 of 1mM or less. 48. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 5%; and wherein the polymeric ROS agent has a molecular weight of at least 1000 Da; and wherein the composition has an SPF of less than 15; and wherein the antioxidant system has an ROS inhibition IC50 of 10mM or less. 49. The composition of any preceding Embodiment, wherein the antioxidant system has an ROS capture IC50 of 10 mM or less.50. The composition of any preceding Embodiment, wherein the antioxidant system has an ROS capture IC50 of 5 mM or less. 51. The composition of any preceding Embodiment, wherein the antioxidant system has an ROS capture IC50 of 1 mM or less. 52. The composition of any preceding Embodiment, wherein the antioxidant system has an ROS inhibition IC50 of 10mM or less and an ROS capture IC50 of 5 mM or less. 53. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 5%; and wherein the polymeric ROS agent has a molecular weight of at least 1000 Da; and wherein the composition has an SPF of less than 15; and wherein the antioxidant system has an ROS inhibition IC50 of 10mM or less; and wherein the antioxidant system has an ROS capture IC50 of 5 mM or less. 54. A composition comprising an antioxidant system, wherein the antioxidant system comprises ROS agents; wherein the ROS agents comprise a polymeric ROS agent and a free ROS agent. 55. A composition comprising an antioxidant system and a skin brightening agent, wherein the antioxidant system comprises ROS agents; wherein the ROS agents comprise a polymeric ROS agent and a free ROS agent. 56. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 500 Da. 57. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 600 Da. 58. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 700 Da. 59. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 800 Da. 60. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 900 Da.61. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 1000 Da. 62. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 1500 Da. 63. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 2000 Da. 64. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 10000 Da. 65. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 20000 Da. 66. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 30000 Da. 67. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 40000 Da. 68. The composition of any preceding Embodiment, wherein the polymeric ROS agent has a molecular weight of at least 50000 Da. 69. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 9%. 70. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 8%. 71. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 7%. 72. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 6%. 73. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 5%. 74. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no more than 4%.75. The composition of any preceding Embodiment, wherein the composition has a %UVA-T of no mor...

Claims

CLAIMS:

1. A topical composition suitable for use as an anti-aging skincare product having: (i) an in vivo SPF of no more than 15; and (ii) a %UVA-T of no more than 10%, and / or a UVA-PF of at least 25, as measured by hybrid diffuse reflectance spectroscopy; and comprising an antioxidant system comprising an ROS capturer and / or an ROS inhibitor.

2. The topical composition of any preceding claim, wherein the antioxidant system comprises a dual-functional ROS agent which is both an ROS capturer and an ROS inhibitor.

3. The topical composition of any preceding claim, wherein the ROS capturer is a free ROS agent.

4. The topical composition of any preceding claim, wherein the free ROS agent is a naturally occurring antioxidant.

5. The topical composition of any preceding claim, wherein the free ROS agent is a polyphenol or carotenoid.

6. The topical composition of any preceding claim, wherein the free ROS agent is a flavonoid, a xanthene, a xanthone, or a stilbenoid, or derivatives and / or combinations thereof.

7. The topical composition of any preceding claim, wherein the free ROS agent is quercetin, naringenin, mangiferin, luteolin, hesperidin, apigenin, or derivatives and / or combinations thereof.

8. The topical composition of any preceding claim, wherein the free ROS agent is quercetin, naringenin, mangiferin, luteolin, or derivatives and / or combinations thereof.

9. The topical composition of any preceding claim, wherein the ROS inhibitor is a polymeric ROS agent.

10. The topical composition of any preceding claim, wherein the polymeric ROS agent is a polymer of Formula 1: X (Formula 1);XA and XB, are each independently absent, or independently selected from X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; X wherein is the repeat unit, wherein each X isfrom X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; and L is the optional linker, which may be a linker moiety or a covalent bond; and X1is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties.

11. The topical composition of any preceding claim, wherein the polymeric ROS agent is a polymer of Formula 1:X (Formula 1); XA and XB, are each independently absent, orindependently selected from X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; X wherein is the repeat unit, wherein each X isfrom X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; and L is the optional linker, which may be a linker moiety or a covalent bond; and X1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties.

12. The topical composition of any preceding claim, wherein at least one of XA and XB is X1; and no instance of X is X1.

13. The topical composition of any preceding claim, wherein one of XA or XB is X1; and no instance of X is X1.

14. The topical composition of any preceding claim, wherein both of XA and XB are X1; and no instance of X is X1.

15. The topical composition of any preceding claim, wherein the repeat unit of Formula 1 corresponds to any one of Formulae 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 1I, 1J, 1K, 1L, 1M, 1N or a combination thereof:wherein: L is a covalent bond or a linker covalently attaching X1 to the remainder of the structure, X1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties, each of X2 – X7 is hydrocarbyl or optionally substituted hydrocarbyl, and each of X8, X9 or X10 is X1, hydrogen, hydrocarbyl or substituted hydrocarbyl.

16. The topical composition of any preceding claim, wherein the repeat unit is selected from Formulae 1A, 1B, 1E, and 1F.

17. The composition of any preceding claim, wherein X1 corresponds to Formula 2G O msubstituted alkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, amino, aryl, arylalkyl, or heterocyclo; and n is 0-5; and each R117 is independently hydroxyl, acyl, acyloxy, alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkoxy, or amino and m is 0-3.

18. The composition of any preceding claim, wherein the polymeric ROS agent is a compound of the Formula Ya: (OH)δα an C1- C10 alkyl; and each δ is independently an integer from 1 to 4.

19. The composition of any preceding claim, wherein the polymeric ROS agent is a compound of the Formula Yb:CH3CH3CH3RγC1-20. The composition of any preceding claim, wherein the polymeric ROS agent is a compound of the Formula Yb: CH3CH3CH3C1-C6 alkyl.

21. The composition of any preceding claim, wherein the polymeric ROS agent is a compound of the Formula Yc: CH3CH3CH3wherein α is an integer from 1 to 5.

22. The composition of any preceding claim, wherein the polymeric ROS agent is a compound of the Formula Y: CH3CH3CH3Si O Si O Si CH323. any Formula 2H-1 wherein eachalkyl, optionally substituted alkenyl, acrylamide, acrylic, acyl, acyloxy, optionally substituted alkoxy, alkoxycarbonyl, amino, aryl, arylalkyl, or heterocyclo; and n is 0-5; and R1141 is alkyl, each R117 is independently hydroxyl, acyl, acyloxy, alkoxycarbonyl, optionally substituted alkyl, optionally substituted alkoxy, or amino and m is 0-3.

24. The composition of any preceding claim wherein the polymeric ROS agent is a compound of the Formula Za:CH3CH3CH3wherein ε is an25. The composition of any prceding claim wherein the polymeric ROS agent is a compound of the Formula Za: CH3CH3CH3wherein ε is an26. The composition of any preceding claim, wherein the polymeric ROS agent is a compound of the Formula Zb:CH3CH3CH327. The composition of any preceding claim, wherein the polymeric ROS agent is a compound of the Formula Z: CH3CH3CH328. The topical composition of any preceding claim, wherein any organic UV filters present in the topical composition are encapsulated.

29. The topical composition of any preceding claim, wherein any organic UV filters present in the topical composition have a molecular weight of at least 500 Da.

30. The topical composition of any preceding claim, wherein any organic UV filters present in the topical composition are substantially non-absorbed.

31. The topical composition of any preceding claim, having a %UVA-T of no more than 5%.

32. The topical composition of any preceding claim, having a %UVA-T of no more than 4%.

33. The topical composition of any preceding claim, having a %UVA-T of no more than 3%.

34. The topical composition of any preceding claim, having a %UVA-T of no more than 2%.

35. The topical composition of any preceding claim, having a %UVA-T of no more than 1%.

36. The topical composition of any preceding claim, having a UVA-PF of at least 35.

37. The topical composition of any preceding claim, having a UVA-PF of at least 40.

38. The topical composition of any preceding claim, having a UVA-PF of at least 45.

39. The topical composition of any preceding claim, having a UVA-PF of at least 50.

40. The topical composition of any preceding claim, wherein the ratio of the UVA-PF of the topical composition to the SPF of the topical composition is at least 2:

1.

41. The topical composition of any preceding claim, wherein the ratio of the UVA-PF of the topical composition to the SPF of the topical composition is at least 3:

1.

42. The topical composition of any preceding claim, wherein the ratio of the UVA-PF of the topical composition to the SPF of the topical composition is at least 4:

1.

43. The topical composition of any preceding claim, wherein the ratio of the UVA-PF of the topical composition to the SPF of the topical composition is at least 5:

1.

44. The topical composition of any preceding claim, wherein the topical composition further comprises no more than two different organic UV filters selected from 1-(4-Methoxyphenyl)-3-(4-tert-butylphenyl)-1,3-propanedione, tris- biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl-N,N-dimethylammonium)-2- hydroxypropane-1-sulphonate, drometrizole trisiloxane, phenylene bis- diphenyltriazine, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3-phenylprop-2- enoate, 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate, hexyl 2-[4- (diethylamino)-2-hydroxybenzoyl]benzoate, 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino)benzoate, 2-phenyl-3H-benzimidazole-5-sulfonic acid, 2- ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4- methoxyphenyl)(2-hydroxyphenyl)methanone, (2-hydroxy-4- methoxyphenyl)(phenyl)methanone, 3,3,5-trimethylcyclohexyl 2- hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2-ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2- hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2- hydroxy-N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4- [(Z)-[7,7-Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3- benzotriazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4- methoxyphenyl)-1,3,5-triazine-2,4-diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3-benzimidazole-4-sulfonate), 2-(2H- benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3-tetramethyl-1- [(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2-ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine- 2,4-diyl)bis(azanediyl)]dibenzoate, 3-(3,4,5-trimethoxybenzylidene)-2,4- pentanedione, diethylhexylsyringylidene malonate, diethylhexyl-2,6-naphthalate, butyloctyl salicylate, tridecyl salicylate, benzotriazolyl dodecyl p-cresol, bis(cyano butylacetate) anthracenediylidene, phenoxyethyl caprylate, tris(PPG-3 benzyl ether) citrate and / or 3-Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, or a salt of any of the aforementioned.

45. The topical composition of any preceding claim, wherein none of 1-(4- Methoxyphenyl)-3-(4-tert-butylphenyl)-1,3-propanedione, tris-biphenyl triazine, 3- (n-p-Methoxycinnamidopropyl-N,N-dimethylammonium)-2-hydroxypropane-1- sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl- 2-cyano-3-(4-methoxyphenyl)-3-phenylprop-2-enoate, 2-ethylhexyl 2-cyano-3,3- diphenylprop-2-enoate, hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate, 4- aminobenzoic acid, 2-ethylhexyl 4-(dimethylamino)benzoate, 2-phenyl-3H- benzimidazole-5-sulfonic acid, 2-ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2- enoate, (2-hydroxy-4-methoxyphenyl)(2-hydroxyphenyl)methanone, (2-hydroxy- 4-methoxyphenyl)(phenyl)methanone, 3,3,5-trimethylcyclohexyl 2- hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2-ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2- hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2- hydroxy-N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4- [(Z)-[7,7-Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3- benzotriazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4- methoxyphenyl)-1,3,5-triazine-2,4-diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3-benzimidazole-4-sulfonate), 2-(2H- benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3-tetramethyl-1- [(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2-ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine- 2,4-diyl)bis(azanediyl)]dibenzoate, 3-(3,4,5-trimethoxybenzylidene)-2,4- pentanedione, diethylhexylsyringylidene malonate, diethylhexyl-2,6-naphthalate, butyloctyl salicylate, tridecyl salicylate, benzotriazolyl dodecyl p-cresol, bis(cyano butylacetate) anthracenediylidene, phenoxyethyl caprylate, tris(PPG-3 benzyl ether) citrate and / or 3-Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, nor any salt of any of the aforementioned, is present at a concentration of 1% or more by weight of the topical composition.

46. The topical composition of any preceding claim, wherein the composition contains substantially no 1-(4-Methoxyphenyl)-3-(4-tert-butylphenyl)-1,3- propanedione, tris-biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl-N,N- dimethylammonium)-2-hydroxypropane-1-sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3- phenylprop-2-enoate, 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate, hexyl 2- [4-(diethylamino)-2-hydroxybenzoyl]benzoate, 4-aminobenzoic acid, 2-ethylhexyl 4-(dimethylamino)benzoate, 2-phenyl-3H-benzimidazole-5-sulfonic acid, 2- ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4- methoxyphenyl)(2-hydroxyphenyl)methanone, (2-hydroxy-4-methoxyphenyl)(phenyl)methanone, 3,3,5-trimethylcyclohexyl 2- hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2- ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2- hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2- hydroxy-N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4- [(Z)-[7,7-Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3- benzotriazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4- methoxyphenyl)-1,3,5-triazine-2,4-diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3-benzimidazole-4-sulfonate), 2-(2H- benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3-tetramethyl-1- [(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2-ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine- 2,4-diyl)bis(azanediyl)]dibenzoate, 3-(3,4,5-trimethoxybenzylidene)-2,4- pentanedione, diethylhexylsyringylidene malonate, diethylhexyl-2,6-naphthalate, butyloctyl salicylate, tridecyl salicylate, benzotriazolyl dodecyl p-cresol, bis(cyano butylacetate) anthracenediylidene, phenoxyethyl caprylate, tris(PPG-3 benzyl ether) citrate and / or 3-Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, or a salt of any of the aforementioned.

47. The topical composition of any preceding claim, wherein the total amount of the free ROS agent in the topical compositions of the invention is from about 0.05% to about 10% (by weight) of the topical composition.

48. The topical composition of any preceding claim, wherein the total amount of the free ROS agent in the topical compositions of the invention is from about 0.5% to about 4% (by weight) of the topical composition.

49. The topical composition of any preceding claim, wherein the total amount of the free ROS agent in the topical compositions of the invention is from about 0.5% to about 3% (by weight) of the topical composition.

50. The topical composition of any preceding claim, wherein the topical composition further comprises one or more additional components, optionally wherein the additional components are selected from water, oils, fats, organic solvents, carriers, thickeners (e.g., ionic or non-ionic thickeners), softeners, opacifiers, stabilizers, film-formers, emulsifiers, emollients, silicones, hydroxy acids, anti-foaming agents, moisturizers, fragrances, preservatives, surfactants, fillers, sequestering agents, polymers, propellants, basifying or acidifying agents, buffering agents, chelating agents, colorants, dyes, self-tanning agents, performance enhancers, sensory enhancers, powders, skin brightening agents, anti-acne agents, anti-aging agents, barrier repair agents, resurfacing agents, oil control agents, exfoliating agents, anti-inflammatory agents, natural extracts, humectants, or any other ingredient usually used in the cosmetics and / or dermatological field, or any combinations thereof.

51. The topical composition of any preceding claim, wherein the formulation is one of oil-in-water (o / w) emulsions, water-in-oil (w / o) emulsions, multiple emulsions (e.g., water-in-oil-in-water emulsions or oil-in-water-in-oil emulsions), microemulsions, high internal phase emulsions (HIPE), water-in-silicone emulsions, PET emulsions, Pickering emulsions, anhydrous lotions or creams, hydrogels, alcoholic gels, lipogels, mono-phase or multi-phase solutions, foams, ointments, plasters, suspensions, powders, creams, cleansers, sticks, soaps and other usual compositions.

52. The topical composition of any preceding claim, wherein the topical composition has a viscosity of from 500 cP to 80,000 cP.

53. The topical composition of any preceding claim, wherein the topical composition has a viscosity of at least 2,000 cP.

54. A method for protecting human skin from oxidative stress, the method comprising applying a composition of any preceding claim to human skin.

55. The method of any preceding claim, wherein the composition is applied as a photo-aging inhibition composition and not as a sunscreen composition.

56. A topical composition having a %UVA-T of no more than 10% and / or a UVA-PF of at least 30 as measured by hybrid diffuse reflectance spectroscopy, an in vivo SPF of less than 15, and comprising an antioxidant system; wherein the antioxidant system comprises ROS agents and the ROS agents comprise a free ROS agent and a polymeric ROS agent; the free ROS agent is a polyphenol or carotenoid; the polymeric ROS is a polymer of Formula 1: X (Formula 1);XA and XB, are each independently absent, or independently selected from X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; X wherein is the repeat unit, wherein each X isfrom X1, hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclyl; and L is the optional linker, which may be a linker moiety or a covalent bond; andX1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties; and wherein the repeat unit of Formula 1 corresponds to any one of Formulae 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 1I, 1J, 1K, 1L, 1M, 1N or a combination thereof:L is a covalent bond or a linker covalently attaching X1 to the remainder of the structure, X1 is selected from the group of carbocyclic and heterocyclic moieties substituted, in turn, by at least one moiety selected from the group consisting of acrylic, acrylamide, acyl, acyloxy, optionally substituted alkoxy, optionally substituted alkenoxy, optionally substituted alkyl, optionally substituted alkenyl, amido, amino, aryl, carbocyclic, cyano, heterocyclic, hydroxyl, and sulfo and sulfonate moieties, each of X2 – X7 is hydrocarbyl or optionally substituted hydrocarbyl, and each of X8, X9 or X10 is X1, hydrogen, hydrocarbyl or substituted hydrocarbyl.

57. A topical composition comprising an antioxidant system; wherein the antioxidant system comprises ROS agents and the ROS agents comprise a free ROS agent and a polymeric ROS agent; the free ROS agent is a polyphenol or carotenoid; the polymeric ROS agent is a polymer of: (a) Formula Ya: (OH)δwherein α is an integer from 1 to 5; Rβis C1-C10 alkyl; each Rγis independently C1-C10 alkyl; and each δ is independently an integer from 1 to 4; or (b) Formula Za:CH3CH3CH3O RζSi O Si O Si wherein ε is an58. A topical composition having a %UVA-T of no more than 5%, an in vivo SPF of less than 15, and comprising an antioxidant system; wherein: the antioxidant system comprises ROS agents and the ROS agents comprise a free ROS agent; the free ROS agent is a polyphenol or carotenoid; wherein the composition contains no more than two different organic UV filters selected from the group consisting of: 1-(4-Methoxyphenyl)-3-(4-tert-butylphenyl)-1,3- propanedione, tris-biphenyl triazine, 3-(n-p-Methoxycinnamidopropyl-N,N- dimethylammonium)-2-hydroxypropane-1-sulphonate, drometrizole trisiloxane, phenylene bis-diphenyltriazine, 2-ethylhexyl-2-cyano-3-(4-methoxyphenyl)-3- phenylprop-2-enoate, 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate, hexyl 2- [4-(diethylamino)-2-hydroxybenzoyl]benzoate, 4-aminobenzoic acid, 2-ethylhexyl 4-(dimethylamino)benzoate, 2-phenyl-3H-benzimidazole-5-sulfonic acid, 2- ethoxyethyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, (2-hydroxy-4- methoxyphenyl)(2-hydroxyphenyl)methanone, (2-hydroxy-4- methoxyphenyl)(phenyl)methanone, 3,3,5-trimethylcyclohexyl 2- hydroxybenzoate, (1R,3R,4S)-p-menthan-3-yl 2-aminobenzoate, (RS)-2- ethylhexyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, 2-ethylhexyl 2- hydroxybenzoate, 5-benzoyl-4-hydroxy-2-methoxybenzene-1-sulfonic acid, 2-hydroxy-N,N-bis(2-hydroxyethyl)ethan-1-aminium 2-hydroxybenzoate, [(3Z)-3-[[4- [(Z)-[7,7-Dimethyl-2-oxo-1-(sulfomethyl)-3- bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1- bicyclo[2.2.1]heptanyl]methanesulfonic acid, (3E)-1,7,7-trimethyl-3-[(4- methylphenyl)methylene]-2-norbornanone, 2,2′-methylenebis[6-(2H-1,2,3- benzotriazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol], 2,2′-[6-(4- methoxyphenyl)-1,3,5-triazine-2,4-diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, disodium 2,2′-(1,4-phenylene)bis(6-sulfo-1H-1,3-benzimidazole-4-sulfonate), 2-(2H- benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3-tetramethyl-1- [(trimethylsilyl)oxy]-1-disiloxanyl]propyl]phenol, 2,2'-dihydroxy-4,4'- dimethoxybenzophenone-5,5'-disulfonic acid, 4-[[4,6-bis[[4-(2-ethylhexoxy- oxomethyl)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzoic acid 2-ethylhexyl ester, bis(2-ethylhexyl) 4,4′-[(6-{[4-(tert-butylcarbamoyl)phenyl]amino}-1,3,5-triazine- 2,4-diyl)bis(azanediyl)]dibenzoate, 3-(3,4,5-trimethoxybenzylidene)-2,4- pentanedione, diethylhexylsyringylidene malonate, diethylhexyl-2,6-naphthalate, butyloctyl salicylate, tridecyl salicylate, benzotriazolyl dodecyl p-cresol, bis(cyano butylacetate) anthracenediylidene, phenoxyethyl caprylate, tris(PPG-3 benzyl ether) citrate and / or 3-Methylbutyl (2E)-3-(4-methoxyphenyl)prop-2-enoate, or a salt of any of the aforementioned.

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