Polyacetamidosaccharides and methods of making and use thereof

Abstract

The present invention relates to a polysaccharide comprising pendant amides, methods of making thereof, and copolymers, nanoparticles, compositions, thermoplastics, and membranes comprising the polysaccharide.

Description

[0001] TITLE OF THE INVENTION POLYACETAMIDOSACCHARIDES AND METHODS OF MAKING AND USE THEREOF

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to U.S. Provisional App. No. 63 / 652,371, filed on May 28, 2024, incorporated herein by reference in its entirety.

[0004] BACKGROUND OF THE INVENTION

[0005] There is presently a growing concern of plastic waste, plastic degradation into microplastics, and waste accumulation and depletion of non-renewable resources in plastic production. Natural polysaccharides play a crucial role in various applications due to their exceptional ability to manage water interactions, making them essential components in hydrogels, lubricants, and coatings (Berradi et al., 2023, Polymers, 15; Dattilo et al., 2023, J. Funct. Biomater., 14; Banalaya et al., 2024, Int. J. Mol. Sci., 25; Harugade et al., 2023, Reactive and Functional Polymers, 191, 105634). However, their broader utility is often hindered by significant challenges, including susceptibility to enzymatic and chemical degradation, primarily due to the instability of ether linkages (Sikorski et al., 2021, Mar. Drugs, 19; Stone et al., 2008, Glycoscience: Chemistry and Chemical Biology, 2325), as well as batch variability and heterogeneity (Xu et al., 2025, J. Am. Chem. Soc., 147, 945). Addressing these limitations requires new strategies to enhance their stability and consistency.

[0006] In addition to these challenges, the polymerization of polysaccharides presents significant difficulties. Enzymatic polymerization, while capable of producing well-defined structures, is highly specific, costly, and often difficult to scale. Traditional chemical polymerization methods, on the other hand, typically proceed in a stepwise manner, resulting in uncontrolled molecular weights, high dispersities, and irregular functionalization (Zia et al., 2016, Int. J. Biol. Macromol., 82, 1028; Galbis et al., 2016, Chem. Rev., 116, 1600; Fenouillot et al., 2010, Polymer Science, 35, 578; Xie et al., 2024, Polymer Chemistry, 15, 412). These limitations make it challenging to achieve consistent and reproducible polysaccharide-based materials, further restricting their broader applicability in advanced material systems. While this issue of controlled polysaccharides is not new, there have been recent breakthroughs in the field that have exciting consequences for glycomaterials (Wu et al., 2023, Nature Chemistry, 15, 1276; Shen et al., 2023, J. Am. Chem. Soc., 145, 15405; Pinilla et al., 2003, Carbohydrate Research, 338, 549; Romero Zalis et al., 2006, Carbohydrate Research, 341, 2973; Koda et al., 2019, ACS Macro Letters, 8, 1456).

[0007] Cellulose acetate is a well-known biodegradable plastic and plastic alternative isolated from plants and can be spun into fibers, molded, and used as thin layer coatings. Cellulose is extracted from renewable resources such as plant processing waste like wood pulp, cotton byproducts, and bamboo. Cellulose acetates are biodegradable, made from renewable resources, maintain properties akin to non-biodegradable plastics, offer functionality without compromise, and are widely utilized in both textile and coatings industries due to their weaving capability and moldability. Being derived from plants and treated with acetic acid, cellulose acetate possesses the unique ability to degrade back into naturally occurring monosaccharides while offering various properties in its polymeric form, in part because of P-1,4 linkages between glucose repeat units.

[0008] Despite these advantages, cellulose acetate’s isolation from plants as a fully formed glycan means that there is limited control over the polymer chain length, dispersity, and no control over the stereochemistry. Due to it being isolated from plants as a fully formed polysaccharide rather than built from monomer building blocks, there are limitations in controlling its macromolecular features that could alter its properties and applications, such as polymer chain length, dispersity, and no control over stereochemistry or three-dimensional (3D) structure. The inability to control its properties with precision due to the isolation process impedes optimization for specific applications, hindering its competitiveness against alternative materials offering tailored performance characteristics.

[0009] Thus, there is a need in the art for saccharide-derived degradable materials and methods to synthesize degradable materials which can serve as plastic alternatives. The inventions provided herein address this need.

[0010] SUMMARY OF THE INVENTION

[0011] Described herein is a polymer comprising a structure represented by General Formula (I):

[0012]

[0013] General Formula (I) wherein:

[0014] X represents 0 or S; ring A represents a C4-C7 cycloalkyl or a C3-C6 heterocycloalkyl;

[0015] R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, or C3-C6 heterocycloalkyl, which can optionally be further substituted; each occurrence of RAindependently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cvaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein any two adjacent RAcan join to form a ring; n represents an integer from 10-500; and m represents an integer from 1 to 10.

[0016] In some examples, R represents a C1-C30 alkyl which is optionally further substituted. In some examples, n is 10. In some examples, the polymer comprises General Formula (lb):

[0017] General Formula (lb), wherein: each R1, R2, R3, R4, R5, R6, R7, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted.

[0018] In some examples, at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises a C1-C30 alkyl ester. In some examples, ring A is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, metabolites thereof, and any combination thereof.

[0019] In some examples, ring A is selected from the group consisting of galactose, glucose, mannose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, furanose, and any stereochemical isomer thereof. In some examples, the polymer is a copolymer comprising a repeat unit of at least two monomers, wherein at least one monomer comprises a monosaccharide. In some examples, the polymer further comprises General Formula (Ic):

[0020] General Formula (Ic), wherein:

[0021] X represents 0 or S;

[0022] R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and each R1, R2, R3, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, Cs-Cyaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted.

[0023] In some examples, at least one of R1, R2, and R3is benzyl. In some examples, the polymer comprises at least one of the following structures:

[0024] Also described herein is a nanoparticle or composition comprising the polymer and a membrane or coating comprising the polymer. Also described herein is a method of synthesizing a polymer comprising the steps of: providing a solution comprising a monomer; adding an initiator to the solution; and polymerizing the monomer to provide a polymer; wherein the monomer is represented by General Formula (II):

[0025] General Formula (II), wherein:

[0026] X represents 0 or S; ring A represents a C4-C7 cycloalkyl or a C3-C6 heterocycloalkyl;

[0027] R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; each occurrence of RAindependently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cvaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein any two adjacent RAcan join to form a ring; and m represents an integer from 1 to 10.

[0028] In some examples, the initiator is represented by General Formula (III):

[0029] General Formula (III) wherein:

[0030] X represents 0 or S;

[0031] R and RNeach independently represent a C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Czaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and

[0032] Y represents a counterion selected from the group consisting of tosylate, triflate, halide, borate, and phosphate.

[0033] In some examples, the initiator is methyl tosylate. In some examples, the solution comprises an organic solvent. In some examples, ring A is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, metabolites thereof, and any combination thereof. In some examples, the monomer represented by General Formula (II) is further represented by General Formula (Ila):

[0034] General Formula (Ila), wherein:

[0035] X represents 0 or S;

[0036] R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and each R1, R2, R3, R4, R5, R6, R7, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises a Cs-Cvaryl.

[0037] In some examples, the monomer represented by General Formula (II) is represented by one of the following structures, or a combination thereof:

[0038] BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The following detailed description of embodiments of the invention will be better understood when read in conjunction with the appended drawings. It should be understood that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings.

[0040] Fig. 1, comprising Fig. 1 A and Fig. IB, depicts representative synthetic schemes for the synthesis of exemplary polymers and monomers. Fig. 1A depicts a proposed mechanistic pathway illustrating SNI and SN2 pathways. Fig. IB depicts representative synthetic schemes for OAc-GlcOx and OBn-GlcOx monomers.

[0041] Fig. 2, comprising Fig. 2A and Fig. 2B, depicts example size exclusion chromatography (SEC) traces of exemplary synthesized polymers. Fig. 2A depicts an SEC trace of different catalysts with the OAc-GlcOx monomer. Fig. 2B depicts an SEC trace of different catalysts with the OBn-GlcOx monomer.

[0042] Fig. 3 depicts exemplary SEC traces monitoring conversion from monomer to polymer in di chloroethane (DCE), acetonitrile (MeCN), and dimethylformamide (DMF).

[0043] Fig. 4, comprising Fig. 4A through Fig. 4D, depicts exemplary kinetics data for a polymerization. Fig. 4A depicts a plot of monomer conversion compared to dispersity. Fig. 4B depicts a plot of monomer conversion kinetics, demonstrating that the representative polymerization follows first-order kinetics. Fig. 4C depicts a reaction scheme of the representative polymerization. Fig. 4D depicts SEC traces of the polymer at various time points of the polymerization.

[0044] Fig. 5 depicts exemplary termination schemes of the polymerization. The left panel shows an exemplary termination mechanism of a weak nucleophile (water) at the 2-position, and the right panel shows potential structures formed from either potential termination by isopropyl alcohol (IP A) at the 5-position or IPA termination at the 2-position.

[0045] Fig. 6 depicts representative data showing the conversion of the second block after addition of MeOx to form poly([OBn-GlcOx]io-block-[MeOx]5o.

[0046] Fig. 7 depicts representative degradation data of homo-poly(OBn-GlcOx), which showed no significant degradation under intense acidic conditions.

[0047] Fig. 8 depicts a representative synthetic scheme for the synthesis of stable oxazoline monomers.

[0048] Fig. 9 depicts a representative polymerization scheme for the polymerization of poly(acetamidosaccharides).

[0049] Fig. 10 depicts screening conditions for the formation of galactose oxazoline monomer. Fig. 11 depicts screening conditions for catalyst and solvent optimization for polymerization.

[0050] Fig. 12 depicts screening results in probing monomer concentration effect on polymerization.

[0051] Fig. 13 depicts other aminosugar derivatives of interest.

[0052] DETAILED DESCRIPTION

[0053] Described herein are compositions of and methods for the synthesis of a polyacetamidosaccharide, uniquely suited for applications in textile and coating industries, biotechnical applications, and food stabilizers or alternative or complementary food gums for the formulation of stable and textured food products.

[0054] Definitions

[0055] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0056] As used herein, each of the following terms has the meaning associated with it in this section.

[0057] The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0058] “About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

[0059] As used herein, the term “organic” includes polymeric materials as well as small molecule organic materials. “Small molecule” refers to any organic material that is not a polymer, and “small molecules” may actually be quite large. Small molecules may include repeat units in some circumstances. For example, using a long chain alkyl group as a substituent does not remove a molecule from the “small molecule” class. Small molecules may also be incorporated into polymers, for example as a pendent group on a polymer backbone or as a part of the backbone. Small molecules may also serve as the core moiety of a dendrimer, which consists of a series of chemical shells built on the core moiety.

[0060] As used herein, the term “alkyl,” by itself or as part of another substituent means, unless otherwise stated, a straight or branched chain hydrocarbon having the number of carbon atoms designated (i.e. Ci-6 means one to six carbon atoms) and including straight, branched chain, or cyclic substituent groups. Examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl, hexyl, and cyclopropylmethyl.

[0061] As used herein, the term “substituted alkyl” means alkyl as defined above, substituted by one, two or three substituents selected from the group consisting of halogen, -OH, alkoxy, -NH2, amino, azido, -N(CH3)2, -C(=O)OH, trifluoromethyl, -C=N, -C(=O)O(Ci-C4)alkyl, -C(=0)NH2, -SO2NH2, -C(=NH)NH2, and -NO2. Examples of substituted alkyls include, but are not limited to, 2,2-difluoropropyl, 2-carboxy cyclopentyl and 3 -chloropropyl.

[0062] As used herein, the term “olefin” encompasses compounds having a C=C bond.

[0063] The term "olefin-based polymer," as used herein, refers to a polymer that contains at least a majority weight percent, based on the weight of the polymer, polymerized olefin (for example, ethylene or propylene), and, optionally, one or more additional comonomers.

[0064] As used herein, the term “heteroalkyl” by itself or in combination with another term means, unless otherwise stated, a stable straight or branched chain alkyl group consisting of the stated number of carbon atoms and one or two heteroatoms selected from the group consisting of 0, N, and S, and wherein the nitrogen and sulfur atoms may be optionally oxidized and the nitrogen heteroatom may be optionally quatemized. The heteroatom(s) may be placed at any position of the heteroalkyl group, including between the rest of the heteroalkyl group and the fragment to which it is attached, as well as attached to the most distal carbon atom in the heteroalkyl group. Examples include -O-CH2-CH2-CH3, -CH2-CH2-CH2-OH, -CH2-CH2-NH-CH3, -CH2-S-CH2-CH3, and -CH2CH2-S(=O)-CH3. Up to two heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3, or -CH2-CH2-S-S-CH3.

[0065] As used herein, the term “alkoxy” employed alone or in combination with other terms means, unless otherwise stated, an alkyl group having the designated number of carbon atoms, as defined above, connected to the rest of the molecule via an oxygen atom, such as, for example, methoxy, ethoxy, 1 -propoxy, 2-propoxy (isopropoxy) and the higher homologs and isomers. As used herein, the term “halo” or “halogen” alone or as part of another substituent means, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom.

[0066] As used herein, the term “cycloalkyl” refers to a mono cyclic or polycyclic non-aromatic radical, wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom. In some examples, the cycloalkyl group is saturated or partially unsaturated. In another embodiment, the cycloalkyl group is fused with an aromatic ring. Cycloalkyl groups include groups having from 3 to 10 ring atoms. Illustrative examples of cycloalkyl groups include, but are not limited to, the following moi eties:

[0067] Monocyclic cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Dicyclic cycloalkyls include, but are not limited to, tetrahydronaphthyl, indanyl, and tetrahydropentalene. Polycyclic cycloalkyls include adamantine and norbornane. The term cycloalkyl includes “unsaturated nonaromatic carbocyclyl” or “nonaromatic unsaturated carbocyclyl” groups, both of which refer to a nonaromatic carbocycle as defined herein, which contains at least one carbon double bond or one carbon triple bond.

[0068] As used herein, the term “heterocycloalkyl” or “heterocyclyl” or “heterocyclic” refers to a cyclic group containing one to four ring heteroatoms each selected from 0, S, and N. In some examples, each heterocycloalkyl group has from 4 to 10 atoms in its ring system, with the proviso that the ring of said group does not contain two adjacent 0 atoms. In another embodiment, the heterocycloalkyl group is fused with an aromatic ring. In some examples, the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen atom may be optionally quatemized. The heterocyclic system may be attached, unless otherwise stated, at any heteroatom or carbon atom that affords a stable structure. A heterocycle may be aromatic or non-aromatic in nature. In some examples, the heterocycle is a heteroaryl. An example of a 3-membered heterocycloalkyl group includes, and is not limited to, aziridine. Examples of 4-membered heterocycloalkyl groups include, and are not limited to, azetidine and a beta lactam. Examples of 5-membered heterocycloalkyl groups include, and are not limited to, pyrrolidine, oxazolidine and thiazolidinedione. Examples of 6-membered heterocycloalkyl groups include, and are not limited to, piperidine, morpholine and piperazine.

[0069] Examples of non-aromatic heterocycles include monocyclic groups such as aziridine, oxirane, thiirane, azetidine, oxetane, thietane, pyrrolidine, pyrroline, pyrazolidine, imidazoline, dioxolane, sulfolane, 2, 3 -dihydrofuran, 2, 5 -dihydrofuran, tetrahydrofuran, thiophane, piperidine, 1,2,3,6-tetrahydropyridine, 1,4-dihydropyridine, piperazine, morpholine, thiomorpholine, pyran,

[0070] 2.3 -dihydropyran, tetrahydropyran, 1,4-dioxane, 1,3-dioxane, homopiperazine, homopiperidine,

[0071] 1.3-dioxepane, 4,7-dihydro-l,3-dioxepin, and hexamethyleneoxide.

[0072] As used herein, the term “aromatic” refers to a carbocycle or heterocycle with one or more polyunsaturated rings and having aromatic character, i.e. having (4n + 2) delocalized 7i (pi) electrons, where n is an integer.

[0073] As used herein, the term “aryl,” employed alone or in combination with other terms, means, unless otherwise stated, a carbocyclic aromatic system containing one or more rings (typically one, two or three rings), wherein such rings may be attached together in a pendent manner, such as a biphenyl, or may be fused, such as naphthalene. Examples of aryl groups include phenyl, anthracyl, and naphthyl.

[0074] As used herein, the term “aryl-(Ci-C3)alkyl” means a functional group wherein a one- to three-carbon alkylene chain is attached to an aryl group, e.g., -CH2CH2- phenyl, -CJh-phenyl (benzyl), aryl-CH - and aryl-CH(CH3)-. The term “substituted aryl-(Ci-C3)alkyl” means an aryl-(Ci-C3)alkyl functional group in which the aryl group is substituted. Similarly, the term “heteroaryl-(Ci-C3)alkyl” means a functional group wherein a one to three carbon alkylene chain is attached to a heteroaryl group, e.g., -CFECIh-pyridyl. The term “substituted heteroaryl-(Ci-C3)alkyl” means a heteroaryl-(Ci-C3)alkyl functional group in which the heteroaryl group is substituted.

[0075] As used herein, the term “heteroaryl” or “heteroaromatic” refers to aryl groups which contain at least one heteroatom selected from N, 0, Si, P, and S; wherein the nitrogen and sulfur atoms may be optionally oxidized, and the nitrogen atom(s) may be optionally quaternized. Heteroaryl groups may be substituted or unsubstituted. A heteroaryl group may be attached to the remainder of the molecule through a heteroatom. A polycyclic heteroaryl may include one or more rings that are partially saturated. Examples include tetrahydroquinoline,

[0076] 2.3-dihydrobenzofuryl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4- imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4- isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3- thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2- benzimidazolyl, 5-indolyl, 1 -isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3- quinolyl, and 6-quinolyl.

[0077] Examples of non-aromatic heterocycles include monocyclic groups such as aziridine, oxirane, thiirane, azetidine, oxetane, thietane, pyrrolidine, pyrroline, imidazoline, pyrazolidine, dioxolane, sulfolane, 2, 3 -dihydrofuran, 2, 5 -dihydrofuran, tetrahydrofuran, thiophane, piperidine, 1,2,3,6-tetrahydropyridine, 1,4-dihydropyridine, piperazine, morpholine, thiomorpholine, pyran,

[0078] 2.3 -dihydropyran, tetrahydropyran, 1,4-dioxane, 1,3-dioxane, homopiperazine, homopiperidine,

[0079] 1.3-dioxepane, 4,7-dihydro-l,3-dioxepin and hexamethyleneoxide.

[0080] Examples of heteroaryl groups also include pyridyl, pyrazinyl, pyrimidinyl (particularly 2- and 4-pyrimidinyl), pyridazinyl, thienyl, furyl, pyrrolyl (particularly 2-pyrrolyl), imidazolyl, thiazolyl, oxazolyl, pyrazolyl (particularly 3- and 5-pyrazolyl), isothiazolyl, 1,2,3-triazolyl,

[0081] 1.2.4-triazolyl, 1,3,4-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl,

[0082] 1.3.4-thiadiazolyl and 1,3,4-oxadiazolyl.

[0083] Examples of polycyclic heterocycles and heteroaryls include indolyl (particularly 3-, 4-, 5-, 6- and 7-indolyl), indolinyl, quinolyl, tetrahydroquinolyl, isoquinolyl (particularly 1- and 5-isoquinolyl), 1,2,3,4-tetrahydroisoquinolyl, cinnolinyl, quinoxalinyl (particularly 2- and 5-quinoxalinyl), quinazolinyl, phthalazinyl, 1,8-naphthyridinyl, 1,4-benzodioxanyl, coumarin, dihydrocoumarin, 1,5-naphthyridinyl, benzofuryl (particularly 3-, 4-, 5-, 6- and 7-benzofuryl),

[0084] 2.3-dihydrobenzofuryl, 1,2-benzisoxazolyl, benzothienyl (particularly 3-, 4-, 5-, 6-, and 7-benzothienyl), benzoxazolyl, benzothiazolyl (particularly 2-benzothiazolyl and 5-benzothiazolyl), purinyl, benzimidazolyl (particularly 2-benzimidazolyl), benzotriazolyl, thioxanthinyl, carbazolyl, carbolinyl, acridinyl, pyrrolizidinyl, and quinolizidinyl.

[0085] As used herein, the term “substituted” means that an atom or group of atoms has replaced hydrogen as the substituent attached to another group. The term “substituted” further refers to any level of substitution, namely mono-, di-, tri-, tetra-, or penta-substitution, where such substitution is permitted. The substituents are independently selected, and substitution may be at any chemically accessible position. In some examples, the substituents vary in number between one and four. In another embodiment, the substituents vary in number between one and three. In yet another embodiment, the substituents vary in number between one and two.

[0086] As used herein, the term “optionally substituted” means that the referenced group may be substituted or unsubstituted. In some examples, the referenced group is optionally substituted with zero substituents, i.e., the referenced group is unsubstituted. In another embodiment, the referenced group is optionally substituted with one or more additional group(s) individually and independently selected from groups described herein.

[0087] In some examples, the substituents are independently selected from the group consisting of oxo, halogen, -CN, -NH2, -OH, -NH(CH3), -N(CH3)2, alkyl (including straight chain, branched and / or unsaturated alkyl), substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, fluoro alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkoxy, fluoroalkoxy, -S-alkyl, S(=0)2alkyl, S(=0)2N[H, alkyl, or aryl], - C(=O)NH[substituted or unsubstituted alkyl, or substituted or unsubstituted phenyl], - C(=0)N[H or substituted or unsubstituted alkyl or aryl]2, -OC(=O)N[substituted or unsubstituted alkyl]2, -NHC(=O)NH[substituted or unsubstituted alkyl, or substituted or unsubstituted phenyl], -NHC(=O)alkyl, -N[substituted or unsubstituted alkyl]C(=O)[substituted or unsubstituted alkyl], -NHC(=0) [substituted or unsubstituted alkyl], -C(OH)[substituted or unsubstituted alkyl]2, and -C(NH2)[substituted or unsubstituted alkyl]2. In another example, an optional substituent is selected from oxo, fluorine, chlorine, bromine, iodine, -CN, -NH2, -OH, - NH(CH3), -N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, -CF3, -CH2CF3, -0CH3, -OCH2CH3, - OCH(CH3)2, -0CF3, - OCH2CF3, -S(=O)2-CH3, -C(=0)NH2, -C(=0)-NHCH3, - NHC(=0)NHCH3, -C(=0)CH3, -0N(0)2, and -C(=0)0H. In some examples, the substituents are independently selected from the group consisting of C1-6 alkyl, -OH, C1-6 alkoxy, halo, amino, acetamido, oxo and nitro. As used herein, where a substituent is an alkyl or alkoxy group, the carbon chain may be branched, straight or cyclic.

[0088] As used herein, the term “protected,” as used herein, refers to the presence of a “protecting group” or moiety that prevents reaction of the chemically reactive functional group under certain reaction conditions. The protecting group will vary depending on the type of chemically reactive group being protected. By way of example only, (i) if the chemically reactive group is an amine or a hydrazide, the protecting group may be selected from tertbutyloxycarbonyl (t-Boc) and 9-fluorenylmethoxycarbonyl (Fmoc); (ii) if the chemically reactive group is a thiol, the protecting group may be orthopyridyldisulfide; and (iii) if the chemically reactive group is a carboxylic acid, such as butanoic or propionic acid, or a hydroxyl group, the protecting group may be benzyl or an alkyl group such as methyl, ethyl, or tert-butyl. Additionally, protecting groups include, but are not limited to, photolabile groups, such as Nvoc and MeNvoc, and other protecting groups known in the art. Other protecting groups are described in Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, N.Y., 1999.

[0089] The term “derivative” refers to a small molecule that differs in structure from the reference molecule but retains the essential properties of the reference molecule. A derivative may change its interaction with certain other molecules relative to the reference molecule. A derivative molecule may also include a salt, an adduct, tautomer, isomer, or other variant of the reference molecule.

[0090] The term “tautomers” are constitutional isomers of organic compounds that readily interconvert by a chemical process (tautomerization).

[0091] The term “isomers” or “stereoisomers” refer to compounds, which have identical chemical constitution, but differ with regard to the arrangement of the atoms or groups in space.

[0092] As used herein, the term “polymer” refers to a molecule composed of repeating structural units typically connected by covalent chemical bonds. The term “polymer” is also meant to include the terms copolymer and oligomers.

[0093] As used herein, the term “polymerization” refers to at least one reaction that consumes at least one functional group in a monomeric molecule (or monomer), oligomeric molecule (or oligomer) or polymeric molecule (or polymer), to create at least one chemical linkage between at least two distinct molecules (e.g., intermolecular bond), at least one chemical linkage within the same molecule (e.g., intramolecular bond), or any combination thereof. A polymerization reaction may consume between about 0% and about 100% of the at least one functional group available in the system. In some examples, polymerization of at least one functional group results in about 100% consumption of the at least one functional group. In another example, polymerization of at least one functional group results in less than about 100% consumption of the at least one functional group. As used herein, the term “polymer segment” means and includes a grouping of multiple monomer units of a single type (i.e., a homopolymer segment) or multiple types (i.e., a copolymer segment) of constitutional units into a continuous region of a polymer block that are of a length that is insufficient for microphase separation to inherently occur with other segments in the same block type.

[0094] As used herein, the term “block copolymer” means and includes a polymer composed of chains where each chain contains two or more polymer blocks as defined above and at least two of the blocks are of sufficient segregation strength (e.g., zN> l 0) for those blocks to phase separate. A wide variety of block polymers are contemplated herein including diblock copolymers (i.e., polymers including two polymer blocks), triblock copolymers (i.e., polymers including three polymer blocks), multiblock copolymers (i.e., polymers including more than three polymer blocks), and combinations thereof.

[0095] As used herein, a “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal's health continues to deteriorate.

[0096] As used herein, a “disorder” in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal's state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal's state of health.

[0097] As used herein with respect to the compositions of the invention, “biologically active” means that the compositions elicit a biological response in a mammal that can be monitored and characterized in comparison with an untreated mammal.

[0098] As used herein, the term “treating” means ameliorating the effects of, or delaying, halting or reversing the progress of a disease or disorder. The word encompasses reducing the severity of a symptom of a disease or disorder and / or the frequency of a symptom of a disease or disorder.

[0099] As used herein, the term “prevent” or “prevention” means no disorder or disease development if none had occurred, or no further disorder or disease development if there had already been development of the disorder or disease. Also considered is the ability of one to prevent some or all of the symptoms associated with the disorder or disease. Disease and disorder are used interchangeably herein. As used herein, the term “medical intervention” means a set of one or more medical procedures or treatments that are required for ameliorating the effects of, delaying, halting or reversing a disease or disorder of a subject. A medical intervention may involve surgical procedures or not, depending on the disease or disorder in question. A medical intervention may be wholly or partially performed by a medical specialist, or may be wholly or partially performed by the subject himself or herself, if capable, under the supervision of a medical specialist or according to literature or protocols provided by the medical specialist.

[0100] As used herein, the terms “effective amount” or “therapeutically effective amount” or “pharmaceutically effective amount” of a composition are used interchangeably to refer to the amount of the composition that is sufficient to provide a beneficial effect to the subject to which the composition is administered. The term to “treat,” as used herein, means reducing the frequency with which symptoms are experienced by a patient or subject or administering a composition to reduce the severity with which symptoms are experienced. An appropriate therapeutic amount in any individual case may be determined by one of ordinary skill in the art using routine experimentation.

[0101] By the term “specifically bind” or “specifically binds,” as used herein, is meant that a first molecule (e.g., an antibody) preferentially binds to a second molecule (e.g., a particular antigenic epitope), but does not necessarily bind only to that second molecule.

[0102] As used herein, a “therapeutic” treatment is a treatment administered to a subject who exhibits signs of pathology of a disease or disorder for the purpose of diminishing or eliminating those signs.

[0103] As used herein, the term “pharmaceutically acceptable” refers to a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of the compound, and is relatively non-toxic, i.e., the material may be administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained.

[0104] As used herein, a “pharmaceutically acceptable carrier” means a pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting a compound(s) of the present invention within or to the subject such that it can perform its intended function. Typically, such compounds are carried or transported from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation, and not injurious to the patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carb oxy methyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer’s solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations. As used herein “pharmaceutically acceptable carrier” also includes any and all coatings, antibacterial and antifungal agents, and absorption delaying agents, and the like that are compatible with the activity of the compound, and are physiologically acceptable to the subject. Supplementary active compounds can also be incorporated into the compositions.

[0105] As used herein, the language “pharmaceutically acceptable salt” refers to a salt of the administered compounds prepared from pharmaceutically acceptable non-toxic acids, including inorganic acids, organic acids, solvates, hydrates, or clathrates thereof.

[0106] As used herein, the term “subject” refers to a human or another mammal (e.g., primate, dog, cat, goat, horse, pig, mouse, rat, rabbit, and the like) that can have a disease, disorder, or condition; or be at risk for developing a disease, disorder, or condition; but may or may not have a disease, disorder, or condition or be at risk for developing a disease, disorder, or condition. The subject may be a human being. In such embodiments, the subject is often referred to as an “individual” or a “patient.” The terms “individual” and “patient” do not denote a particular age.

[0107] As used here, “biocompatible” refers to any material, which, when implanted in a mammal, does not provoke an adverse response in the mammal. A biocompatible material, when introduced into an individual, is not toxic or injurious to that individual, nor does it induce immunological rejection of the material in the mammal.

[0108] The term “biodegradable” includes polymers, compositions and formulations, such as those described herein, that are intended to degrade during use. Biodegradable polymers typically differ from non-biodegradable polymers in that the former may be degraded during use. In some examples, such use involves in vivo use, such as in vivo therapy. In another embodiment, such use involves in vitro use. In general, biodegradation involves the degradation of a biodegradable polymer into its component subunits, or digestion, e.g., by a biochemical process, of the polymer into smaller, non-polymeric subunits. Two types of biodegradation may generally be identified. For example, biodegradation may involve cleavage of bonds (whether covalent or otherwise) in the polymer backbone. In such biodegradation, monomers and oligomers typically result, and even more typically, such biodegradation occurs by cleavage of a bond connecting one or more of subunits of a polymer. Further, biodegradation may involve cleavage of a bond (whether covalent or otherwise) internal to side chain or that connects a side chain to the polymer backbone. For example, a therapeutic agent or other chemical moiety attached as a side chain to the polymer backbone may be released by biodegradation. In some examples, at least one type of biodegradation may occur during use of a polymer. As used herein, the term “biodegradation” encompasses all known types of biodegradation.

[0109] As used herein, the terms “biocompatible polymer” and “biocompatibility” when used in relation to polymers are recognized in the art. For example, biocompatible polymers include polymers that are generally neither toxic to the host, nor degrade (if the polymer degrades) at a rate that produces monomeric or oligomeric subunits or other byproducts at toxic concentrations in the host. In some examples, biodegradation generally involves degradation of the polymer in a host, e.g., into its monomeric subunits, which may be known to be effectively non-toxic. Intermediate oligomeric products resulting from such degradation may have different toxicological properties, however, or biodegradation may involve oxidation or other biochemical reactions that generate molecules other than monomeric subunits of the polymer. Consequently, In some examples, toxicology of a biodegradable polymer intended for in vivo use, such as implantation or injection into a patient, may be determined after one or more toxicity analyses. It is not necessary that any subject composition have a purity of 100% to be deemed biocompatible; indeed, it is only necessary that the subject compositions be biocompatible as set forth above. Hence, a subject composition may comprise polymers comprising 99%, 98%, 97%, 96%, 95%, 90%, 85%, 80%, 75% or even less of biocompatible polymers, e.g., including polymers and other materials and excipients described herein, and still be biocompatible. Several references to integers and R, R1, R2, R3, R4, R5, R6, etc. are made in chemical structures and moieties disclosed and described herein. Any description of integers and R, R1, R2, R3, R4, R5, R6, etc. in the specification is applicable to any structure or moiety reciting integers and R, R1, R2, R3, R4, R5, R6, etc. respectively.

[0110] Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.

[0111] The polymers, compositions, and / or methods described herein were developed, in part, to overcome the challenge of polymer design control. The approach involves utilizing widely recognized 1,2-aminosugar oxazolines to synthesize a polysaccharide featuring 1,2-pendant amide linkages. Cationic ring-opening polymerization (CROP) initiators have led to the production of a significant 179-mer of the present polysaccharide. CROP has further allowed the control of various parameters of the polymers, such as contour length, dispersity, and eventually monosaccharide identity, allowing for testing of physical properties as a result of variations in the polymers. A current focus is on exploring the physical and material properties of these polymers, as well as aiming to achieve higher molecular weights.

[0112] The polymers and compositions presented herein are completely novel and afford a saccharide backbone linked through pendant amide linkages. The polymers and compositions are constructed in such a way that allows for precise control over the contour length and dispersity of the polymer and the potential for changing the sugar identity, factors which limit the use of cellulose acetate for broader applications. Representative polymers can be composed of glucose monomers that are N-linked through pendant amides to afford an acetylated polysaccharide. Monomers require only a two-step synthesis from the starting glucosamine with relatively little purification before polymerization required.

[0113] The invention described herein not only confronts the rising concern surrounding plastics but also enhances the adaptability of a widely utilized material. The precise control offered by the polymers, compositions, and method herein overcome the limitations that have restrained the broader applications of cellulose acetate and will pave the way for a set of materials and methods that meet the evolving demands of satisfying diverse industries while mitigating damaging environmental impacts. Cationic ring-opening polymerization (CROP) has been used to create a 179-mer poly(acetamidosaccharide), alongside lower molecular weights ranging from 15-mers to 60-mers.

[0114] Compositions

[0115] Described herein is a polymer comprising a structure represented by General Formula (I):

[0116] General Formula (I) wherein:

[0117] X represents 0 or S; ring A represents C4-C7 cycloalkyl or C3-C6 heterocycloalkyl; R represents amide, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, or C3-C6 heterocycloalkyl, which can optionally be further substituted; each occurrence of RAindependently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein any two adjacent RAcan join to form a ring; n represents an integer from 10-500; and m represents an integer from 1 to 10. As used herein, the term “combinations thereof’ may refer to the covalent linking or combination of more than one substituent in any sequence with no limitation on the maximum number of substituents which may be combined. For example, if RArepresents a combination of a Ci alkyl and a Ce aryl, RAmay be a benzyl group (Ci alkyl-Ce aryl) or a tolyl group (Ce aryl- Ci alkyl).

[0118] In some examples, R represents C1-C30 alkyl which is optionally further substituted. In some examples, R is methyl. In some examples, R is a linear alkyl. In some examples, R is a branched alkyl.

[0119] In some examples, m is at least 1. In some examples, at least one RArepresents C1-C30 alkyl ester. In some examples, at least one RArepresents methyl alkanoate.

[0120] In some examples, n is between 1 and 10. In some examples, n is about 10. In some examples, n is greater than about 10. In some examples, n is greater than about 500. In some examples, n is an integer from 10-500. In some examples, n is an integer from 10-490. In some examples, n is an integer from 10-480. In some examples, n is an integer from 10-470. In some examples, n is an integer from 10-460. In some examples, n is an integer from 10-450. In some examples, n is an integer from 10-440. In some examples, n is an integer from 10-430, In some examples, n is an integer from 10-420. In some examples, n is an integer from 10-410. In some examples, n is an integer from 10-400. In some examples, n is an integer from 10-390. In some examples, n is an integer from 10-380. In some examples, n is an integer from 10-370. In some examples, n is an integer from 10-360. In some examples, n is an integer from 10-350. In some examples, n is an integer from 10-340. In some examples, n is an integer from 10-330, In some examples, n is an integer from 10-320. In some examples, n is an integer from 10-310. In some examples, n is an integer from 10-300. In some examples, n is an integer from 10-290. In some examples, n is an integer from 10-280. In some examples, n is an integer from 10-270. In some examples, n is an integer from 10-260. In some examples, n is an integer from 10-250. In some examples, n is an integer from 10-240. In some examples, n is an integer from 10-230. In some examples, n is an integer from 10-220. In some examples, n is an integer from 10-210. In some examples, n is an integer from 10-200. In some examples, n is an integer from 10-190. In some examples, n is an integer from 10-180. In some examples, n is an integer from 10-170. In some examples, n is an integer from 10-160. In some examples, n is an integer from 10-150. In some examples, n is an integer from 10-140. In some examples, n is an integer from 10-130. In some examples, n is an integer from 10-120. In some examples, n is an integer from 10-110. In some examples, n is an integer from 10-100. In some examples, n is an integer from 10-90. In some examples, n is an integer from 10-80. In some examples, n is an integer from 10-70. In some examples, n is an integer from 10-60. In some examples, n is an integer from 50-500. In some examples, n is an integer from 50-490. In some examples, n is an integer from 50-480. In some examples, n is an integer from 50-470. In some examples, n is an integer from 50-460. In some examples, n is an integer from 50-450. In some examples, n is an integer from 50-440. In some examples, n is an integer from 50-430. In some examples, n is an integer from 50-420. In some examples, n is an integer from 50-450. In some examples, n is an integer from 50-400. In some examples, n is an integer from 50-390. In some examples, n is an integer from 50-380. In some examples, n is an integer from 50-370. In some examples, n is an integer from 50-360. In some examples, n is an integer from 50-350. In some examples, n is an integer from 50-340. In some examples, n is an integer from 50-330. In some examples, n is an integer from 50-320. In some examples, n is an integer from 50-310. In some examples, n is an integer from 50-300. In some examples, n is an integer from 50-290. In some examples, n is an integer from 50-280. In some examples, n is an integer from 50-270. In some examples, n is an integer from 50-260, In some examples, n is an integer from 50-250. In some examples, n is an integer from 50-240. In some examples, n is an integer from 50-230. In some examples, n is an integer from 50-220. In some examples, n is an integer from 50-210. In some examples, n is an integer from 50-200. In some examples, n is an integer from 50-190. In some examples, n is an integer from 50-180. In some examples, n is an integer from 50-170. In some examples, n is an integer from 50-160, In some examples, n is an integer from 50-150. In some examples, n is an integer from 50-140. In some examples, n is an integer from 50-130. In some examples, n is an integer from 50-120. In some examples, n is an integer from 50-110. In some examples, n is an integer from 50-500. In some examples, n is an integer from 50-90. In some examples, n is an integer from 50-80. In some examples, n is an integer from 50-70. In some examples, n is an integer from 50-60. In some examples, n is an integer from 10-50. In some examples, n is an integer from 10-40. In some examples, n is an integer from 10-30. In some examples, n is an integer from 10-20. In some examples, n is an integer from 10-15. In some examples, n is an integer from 100-500. In some examples, n is an integer from 100-490. In some examples, n is an integer from 100-480. In some examples, n is an integer from 100-470. In some examples, n is an integer from 100-460. In some examples, n is an integer from 100-450. In some examples, n is an integer from 100- 440. In some examples, n is an integer from 100-430. In some examples, n is an integer from 100-420. In some examples, n is an integer from 100-410. In some examples, n is an integer from 100-400. In some examples, n is an integer from 100-390. In some examples, n is an integer from 100-380. In some examples, n is an integer from 100-370. In some examples, n is an integer from 100-360. In some examples, n is an integer from 100-350. In some examples, n is an integer from 100-340. In some examples, n is an integer from 100-330. In some examples, n is an integer from 100-320. In some examples, n is an integer from 100-310. In some examples, n is an integer from 100-300. In some examples, n is an integer from 100-290. In some examples, n is an integer from 100-280. In some examples, n is an integer from 100-270. In some examples, n is an integer from 100-260. In some examples, n is an integer from 100- 250. In some examples, n is an integer from 100-240. In some examples, n is an integer from 100-230. In some examples, n is an integer from 100-220. In some examples, n is an integer from 100-210. In some examples, n is an integer from 100-200.

[0121] In some examples, the polymer comprising a structure of General Formula (I) further comprises General Formula (la):

[0122] General Formula (la), wherein: RNrepresents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted. In some examples, RNis a piperidine, which is optionally further substituted. In some examples, RNis a pyridine, which is optionally further substituted. In some examples, RNis a methyl. In some examples, RNcomprises at least one heteroatom.

[0123] In some examples, ring A is a carbohydrate. In some examples, the N is bonded to Ci and C2 of the carbohydrate. In some examples, the carbohydrate is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, metabolites thereof, and any combination thereof

[0124] Exemplary carbohydrates include, but are not limited to, monosaccharides including trioses (such as: ketotriose (dihydroxyacetone); aldotriose (glyceraldehyde)); tetroses which include: ketotetrose (such as: erythrulose) and aldotetroses (such as:erythrose, threose); pentoses which include: ketopentose (such as:ribulose, xylulose) aldopentose (such as:ribose, arabinose, xylose, lyxose), deoxy sugar (such as: deoxyribose), furanose, cytidine; hexoses which include: ketohexose (such as:psicose, fructose, sorbose, tagatose), aldohexose (such as: allose, altrose, glucose, mannose, gulose, idose, galactose, talose), deoxy sugar (such as: fucose, fuculose, rhamnose); heptose (such as: sedoheptulose); octose; nonose (such as: neuraminic acid); disaccharides which include: sucrose; lactose; maltose; trehalose; turanose; cellobiose; kojiboise; nigerose; isomaltose; and palatinose; trisaccharides which include: melezitose; and maltotriose; oligosaccharides that include: com syrups and maltodextrin; polysaccharides that include: glucan (such as dextrin, dextran, beta-glucan), glycogen, mannan, galactan, and starch (such as those from corn, wheat, tapioca, rice, and potato, including amylose and amylopectin; and metabolites that include uronic acid, glucuronic acid, gluconic acid, and isosaccharinic acid. The carbohydrates can be aminated or acetylated or natural or modified or gelatinized; or combinations thereof. Carbohydrates also include source of sweeteners such as honey, maple syrup, glucose (dextrose), corn syrup, corn syrup solids, high fructose corn syrups, crystalline fructose, juice concentrates, dextrose polymers, malt syrup, rice syrup solids, sorghum syrup, refiner syrup, crystalline fructose, brown or invert sugars, molasses, or other grain / nut syrups consisting of rice syrup, agave syrup, palm syrup, and crystalline juice.

[0125] In some examples, ring A is selected from the group consisting of galactose, glucose, mannose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, furanose, and any stereochemical isomer thereof. In some examples, the carbohydrate comprises glucose. In some examples, ring A comprises galactose. In some examples, ring A comprises mannose. In some examples, ring A is a racemate. In some examples, ring A is derived from commercially available sources. In some examples, ring A is extracted from food.

[0126] In some examples, the polymer comprising a structure of General Formula (I) further comprises General Formula (lb):

[0127] General Formula (lb), wherein: each R1, R2, R3, R4, R5, R6, R7, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cyaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C -C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted.

[0128] In some examples, the polymer comprising a structure of General Formula (I) further comprises General Formula (Ic):

[0129] General Formula (Ic), wherein: X represents 0 or S; R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cyaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and each R1, R2, R3, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, Cs-C7aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3- Ce heterocycloalkyl, or combinations thereof, which can optionally be further substituted. In some examples, at least one of R1, R2, and R3are a combination of a C1-C30 alkyl and a C5-C7 aryl, such as benzyl or homobenzyl.

[0130] In some examples, the polymer comprising a structure of General Formula (I) further comprises General Formula (Id):

[0131] General Formula (Id), wherein: X represents 0 or S; R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cv aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C -C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and each R1, R2, R3, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, Cs-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3- Ce heterocycloalkyl, or combinations thereof, which can optionally be further substituted.

[0132] In some examples, the polymer comprises more than 50%, 60%, 70%, 80%, 90%, or 99% ^-linkages, or bonds above the plane of the ring on the anomeric carbon, relative to a- linkages, or bonds below the plane of the ring on the anomeric carbon. In some examples, the polymer comprises about 100% P-linkages. In some examples, the polymer comprises less than 50%, 60%, 70%, 80%, 90%, or 99% a-linkages.

[0133] In some examples, the polymer comprises at least one of the following structures:

[0134] wherein: X represents 0 or S; R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cv aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C -C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and each R1, R2, R3, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C5-C? aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3- Ce heterocycloalkyl, or combinations thereof, which can optionally be further substituted. In some examples, the polymer is a copolymer comprising each of the above structures.

[0135] In some examples, the polymer backbone is unsaturated. In some examples, the polymer backbone is rigid. In some examples, the polymer backbone is partially saturated. In some examples, the polymer backbone is saturated. In some examples, the polymer backbone is flexible. In some examples, the polymer backbone comprises one or more pendant hydroxyl groups. In some examples, the polymer backbone is functionalizable. In some examples, the polymer backbone has an end group comprising a compound selected from the group consisting of a fluorophore, a terminal alkene, a benzyl group, an amino group, a therapeutic small molecule, and combinations thereof.

[0136] In some examples, the polymer forms higher order assemblies. In some examples, the polymer forms secondary structures. In some examples, the polymer comprises exposed hydrophobic pockets. In some examples, the polymer forms nanoassemblies. In some examples, the polymer participates in intramolecular hydrogen bonding. In some examples, the polymer participates in intermolecular hydrogen bonding.

[0137] In some examples, the polymer is a copolymer. In some examples, the polymer is a copolymer comprising a repeat unit of at least two monomers, wherein at least one monomer comprises glucose. In some examples, the polymer is a block copolymer. Other exemplary copolymers include, but are not limited to, random copolymers, statistical copolymers, alternating copolymers, stereoblock copolymers, gradient copolymers, graft copolymers, star copolymers, and combinations thereof. In some examples, the polymer comprises a monomer comprising an amide group. In some examples, the polymer comprises a monomer which does not comprise a carbohydrate. In some examples, the polymer comprises a monomer which comprises a hydroxyl capped linker. In some examples, the polymer comprises a monomer which comprises a linker bonded to a protecting group. In some examples, the carbohydrate is acetylated.

[0138] In some examples, the polymer is insoluble in water. In some examples, the polymer is hydrophilic. In some examples, the polymer is brittle when exposed to water. In some examples, the polymer is brittle. In some examples, the polymer forms an organogel when in contact with an organic solvent.

[0139] Exemplary organic solvents include, but are not limited to, acetic acid, acetone, acetonitrile, alkanes (e.g., hexanes, heptane), amyl acetate, butanol, butyl acetate, chlorobenzene, chloroform, cumene, cyclohexane, 1,2-di chloroethene, di chloromethane, diethyl ether, dimethoxy ethane, dimethylacetamide, dimethylformamide, dimethyl sulfoxide, 1,4- dioxane, ethanol, 2-ethoxyethanol, ethyl acetate, ethyl nitrate, ethyleneglycol, formic acid, hydrazine, isopropanol, methanol, methyl acetate, 2 -methyl- 1 -butanol, 2-methyl-l -propanol, methylbutyl ketone, methylcyclohexane, methylethyl ketone, methylpyrrolidone, methyl tertbutyl ether, nitromethane, propanol, propyl acetate, sulfolane, sarcosine, tetrahydrofuran, tetralin, toluene, 1,1,2-tricholoroethane, tri ethylamine, urea, xylene, and any combination thereof.

[0140] Described herein are applications of the polymer such as a thermoplastic comprising the polymer, or a membrane comprising the polymer. In some examples, the thermoplastic has a glass transition temperature greater than room temperature. In some examples, the thermoplastic does not have a glass transition temperature.

[0141] In some examples, the membrane selectively traps particles. In some examples, the membrane selectively traps particles in a solution. Exemplary solutions include, but are not limited to, drinking water, commercial water, mineral water, well water, and spring water. In some examples, the membrane selectively removes undesired particles in water. Exemplary undesired particles include, but are not limited to, sediment, bacteria, metals, perfluoroalkyl substituents, and polyfluoroalkyl substances.

[0142] Also described herein are compositions and formulations comprising the polymer for drug delivery, hydrogels, tissue engineering scaffolds, food stabilizers, and industrial additives. In some examples, the composition is a biodegradable composition. In some examples, the composition is a medical biodegradable composition. In some examples, the composition is a nanoparticle.

[0143] In some examples, the polymer is bound to a therapeutic agent. There is no limit on the nature or identity of the therapeutic agent. Exemplary therapeutic agents include, but are not limited to, monoclonal antibodies; immunomodulatory agents, including agents that cause T and B cell activation, proliferation, and / or maturation; agents that bring about innate immune system activation, proliferation and / or maturation (e.g., JNK, MAPK, ERK, NK kappa B pathway agonists or antagonists, and monocyte, neutrophil, or macrophage agonists or antagonists); matrix metalloproteinase inhibitors; heat shock protein agonists or antagonists; alpha synuclein inhibitors; chelating agents; diuretics; alpha 1 antitrypsin modulators; purinoceptor agonists or antagonists; cyclooxygenase 2 inhibitors; DNA gyrase inhibitors; natural killer cell and natural killer T cell agonists or antagonists; cathepsin class agonists or antagonists; antioxidant therapy agents; rho-associated kinase inhibitors; myosin inhibitors; phosphatidylinositol 3 kinase inhibitors and related molecules; nitric oxide synthase agonists or antagonists; nitric oxide agonists or antagonists; ion channel function or trafficking modulators; surfactants, in particular, lung surfactants; cannabinoid receptor modulators; complement system inhibitors; IgE receptor antagonists; G protein-coupled receptor agonists or antagonists; chemokines; chemokine receptor agonists or antagonists; cytokines; cytokine receptor agonists or antagonists; arachidonic acid agonists or antagonists; inflammation mediators; STAT6 inhibitors; histamine or leukotriene agonists or antagonists; calcineurin agonists or antagonists; and any combination thereof.

[0144] In various aspects, the composition comprises: one or more polymers of provided herein and one or more stabilizers. In other aspects, the composition comprises: one or more nanoparticles of the present invention and one or more stabilizers. In various embodiments, the stabilizer to nanoparticle weight ratio is less than 50%. In some examples, the stabilizer comprises a biocompatible polymer. Examples of stabilizers include, but are not limited to, biocompatible polymer, a biodegradable polymer, a multifunctional linker, starch, modified starch, and starch derivatives, gums, including but not limited to polymers, polypeptides, albumin, amino acids, thiols, amines, carboxylic acid and combinations or derivatives thereof, citric acid, xanthan gum, alginic acid, other alginates, benitoniite, veegum, agar, guar, locust bean gum, gum arabic, quince psyllium, flax seed, okra gum, arabinoglactin, pectin, tragacanth, scleroglucan, dextran, amylose, amylopectin, dextrin, etc., cross-linked polyvinylpyrrolidone, ion-exchange resins, potassium polymethacrylate, carrageenan (and derivatives), gum karaya and biosynthetic gum, polycarbonates (linear polyesters of carbonic acid); microporous materials (bisphenol, a microporous polyvinylchloride), micro-porous polyamides, microporous modacrylic copolymers, microporous styrene-acrylic and its copolymers); porous polysulfones, halogenated poly(vinylidene), polychloroethers, acetal polymers, polyesters prepared by esterification of a dicarboxylic acid or anhydride with an alkylene polyol, poly(alkylenesulfides), phenolics, polyesters, asymmetric porous polymers, cross-linked olefin polymers, hydrophilic microporous homopolymers, copolymers or interpolymers having a reduced bulk density, and other similar materials, poly(urethane), cross-linked chain-extended poly(urethane), poly(imides), poly(benzimidazoles), collodion, regenerated proteins, semi-solid cross-linked poly (vinyl pyrrolidone), monomeric, dimeric, oligomeric or long-chain, copolymers, block polymers, block co-polymers, polymers, PEG, dextran, modified dextran, polyvinylalcohol, and polyvinylpyrollidone.

[0145] The compositions are formulated in a pharmaceutically acceptable excipient, such as wetting agents, buffers, disintegrants, binders, fillers, flavoring agents and liquid carrier media such as sterile water, water / ethanol etc. The compositions should be suitable for administration either by topical administration or injection or inhalation or catheterization or instillation or transdermal introduction into any of the various body cavities including the alimentary canal, the vagina, the rectum, the bladder, the ureter, the urethra, the mouth, etc. For oral administration, the pH of the composition is preferably in the acid range (e.g., 2 to 7) and buffers or pH adjusting agents may be used. The contrast media may be formulated in conventional pharmaceutical administration forms, such as tablets, capsules, powders, solutions, dispersion, syrups, suppositories etc.

[0146] The compounds, nanoparticles, or compositions of the invention can be formulated and administered to a subject, as now described. The invention encompasses the preparation and use of pharmaceutical compositions comprising the compound, nanoparticle, and / or compositions of the invention useful for the delivery of a therapeutic agent to a cell. The invention also encompasses the preparation and use of pharmaceutical compositions comprising the compound, nanoparticle, and / or compositions of the invention useful for the treatment of a disease or disorder.

[0147] Such a pharmaceutical composition may consist of the active ingredient alone, in a form suitable for administration to a subject, or the pharmaceutical composition may comprise the active ingredient and one or more pharmaceutically acceptable carriers, one or more additional ingredients, or some combination of these. The active ingredient may be present in the pharmaceutical composition in the form of a physiologically acceptable ester or salt, such as in combination with a physiologically acceptable cation or anion, as is well known in the art.

[0148] The pharmaceutical compositions useful for practicing the invention may be administered to deliver a dose of between about 0.01 ng / kg / day and 500 mg / kg / day.

[0149] In various embodiments, the pharmaceutical compositions useful in the methods of the invention may be administered, by way of example, systemically, parenterally, or topically, such as, in oral formulations, inhaled formulations, including solid or aerosol, and by topical or other similar formulations. In addition to the appropriate therapeutic composition, such pharmaceutical compositions may contain pharmaceutically acceptable carriers and other ingredients known to enhance and facilitate drug administration. Other possible formulations, such as nanoparticles, liposomes, resealed erythrocytes, and immunologically based systems may also be used to administer an appropriate modulator thereof, according to the methods of the invention.

[0150] Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for ethical administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals, patients, and subjects of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals and patients is well understood, and the ordinarily skilled veterinary pharmacologist can design and perform such modification with merely ordinary, if any, experimentation.

[0151] Pharmaceutical compositions that are useful in the methods of the invention may be prepared, packaged, or sold in formulations suitable for oral, rectal, vaginal, parenteral, topical, pulmonary, intranasal, buccal, intravenous, ophthalmic, intrathecal and other known routes of administration. Other contemplated formulations include projected nanoparticles, liposomal preparations, resealed erythrocytes containing the active ingredient, and immunologically-based formulations.

[0152] A pharmaceutical composition of the invention may be prepared, packaged, or sold in bulk, as a single unit dose, or as a plurality of single unit doses. As used herein, a “unit dose” is discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage.

[0153] The relative amounts of the active ingredient, the pharmaceutically acceptable carrier, and any additional ingredients in a pharmaceutical composition of the invention will vary, depending upon the identity, size, and condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100% (w / w) active ingredient.

[0154] In addition to the active ingredient, a pharmaceutical composition of the invention may further comprise one or more additional pharmaceutically active agents.

[0155] Controlled- or sustained-release formulations of a pharmaceutical composition of the invention may be made using conventional technology.

[0156] A formulation of a pharmaceutical composition of the invention suitable for oral administration may be prepared, packaged, or sold in the form of a discrete solid dose unit including, but not limited to, a tablet, a hard or soft capsule, a cachet, a troche, or a lozenge, each containing a predetermined amount of the active ingredient. Other formulations suitable for oral administration include, but are not limited to, a powdered or granular formulation, an aqueous or oily suspension, an aqueous or oily solution, or an emulsion.

[0157] A tablet comprising the active ingredient may, for example, be made by compressing or molding the active ingredient, optionally with one or more additional ingredients. Compressed tablets may be prepared by compressing, in a suitable device, the active ingredient in a free- flowing form such as a powder or granular preparation, optionally mixed with one or more of a binder, a lubricant, an excipient, a surface active agent, and a dispersing agent. Molded tablets may be made by molding, in a suitable device, a mixture of the active ingredient, a pharmaceutically acceptable carrier, and at least sufficient liquid to moisten the mixture. Pharmaceutically acceptable excipients used in the manufacture of tablets include, but are not limited to, inert diluents, granulating and disintegrating agents, binding agents, and lubricating agents. Known dispersing agents include, but are not limited to, potato starch and sodium starch glycolate. Known surface active agents include, but are not limited to, sodium lauryl sulphate. Known diluents include, but are not limited to, calcium carbonate, sodium carbonate, lactose, microcrystalline cellulose, calcium phosphate, calcium hydrogen phosphate, and sodium phosphate. Known granulating and disintegrating agents include, but are not limited to, corn starch and alginic acid. Known binding agents include, but are not limited to, gelatin, acacia, pre-gelatinized maize starch, polyvinylpyrrolidone, and hydroxypropyl methylcellulose. Known lubricating agents include, but are not limited to, magnesium stearate, stearic acid, silica, and talc.

[0158] Tablets may be non-coated or they may be coated using known methods to achieve delayed disintegration in the gastrointestinal tract of a subject, thereby providing sustained release and absorption of the active ingredient. By way of example, a material such as glyceryl monostearate or glyceryl distearate may be used to coat tablets. Further by way of example, tablets may be coated using methods described in U.S. Pat. Nos. 4,256,108; 4,160,452; and 4,265,874 to form osmotically-controlled release tablets. Tablets may further comprise a sweetening agent, a flavoring agent, a coloring agent, a preservative, or some combination of these in order to provide pharmaceutically elegant and palatable preparation.

[0159] Hard capsules comprising the active ingredient may be made using a physiologically degradable composition, such as gelatin. Such hard capsules comprise the active ingredient, and may further comprise additional ingredients including, for example, an inert solid diluent such as calcium carbonate, calcium phosphate, or kaolin.

[0160] Soft gelatin capsules comprising the active ingredient may be made using a physiologically degradable composition, such as gelatin. Such soft capsules comprise the active ingredient, which may be mixed with water or an oil medium such as peanut oil, liquid paraffin, or olive oil.

[0161] Liquid formulations of a pharmaceutical composition of the invention which are suitable for oral administration may be prepared, packaged, and sold either in liquid form or in the form of a dry product intended for reconstitution with water or another suitable vehicle prior to use.

[0162] Liquid suspensions may be prepared using conventional methods to achieve suspension of the active ingredient in an aqueous or oily vehicle. Aqueous vehicles include, for example, water and isotonic saline. Oily vehicles include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin. Liquid suspensions may further comprise one or more additional ingredients including, but not limited to, suspending agents, dispersing or wetting agents, emulsifying agents, demulcents, preservatives, buffers, salts, flavorings, coloring agents, and sweetening agents. Oily suspensions may further comprise a thickening agent.

[0163] Known suspending agents include, but are not limited to, sorbitol syrup, hydrogenated edible fats, sodium alginate, polyvinylpyrrolidone, gum tragacanth, gum acacia, and cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, and hydroxypropylmethylcellulose. Known dispersing or wetting agents include, but are not limited to, naturally-occurring phosphatides such as lecithin, condensation products of an alkylene oxide with a fatty acid, with a long chain aliphatic alcohol, with a partial ester derived from a fatty acid and a hexitol, or with a partial ester derived from a fatty acid and a hexitol anhydride (e.g. polyoxyethylene stearate, heptadecaethyleneoxycetanol, polyoxyethylene sorbitol monooleate, and polyoxyethylene sorbitan monooleate, respectively). Known emulsifying agents include, but are not limited to, lecithin and acacia. Known preservatives include, but are not limited to, methyl, ethyl, or n-propyl-para-hydroxybenzoates, ascorbic acid, and sorbic acid. Known sweetening agents include, for example, glycerol, propylene glycol, sorbitol, sucrose, and saccharin. Known thickening agents for oily suspensions include, for example, beeswax, hard paraffin, and cetyl alcohol. Liquid solutions of the active ingredient in aqueous or oily solvents may be prepared in substantially the same manner as liquid suspensions, the primary difference being that the active ingredient is dissolved, rather than suspended in the solvent. Liquid solutions of the pharmaceutical composition of the invention may comprise each of the components described with regard to liquid suspensions, it being understood that suspending agents will not necessarily aid dissolution of the active ingredient in the solvent. Aqueous solvents include, for example, water and isotonic saline. Oily solvents include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin.

[0164] Powdered and granular formulations of a pharmaceutical preparation of the invention may be prepared using known methods. Such formulations may be administered directly to a subject, used, for example, to form tablets, to fill capsules, or to prepare an aqueous or oily suspension or solution by addition of an aqueous or oily vehicle thereto. Each of these formulations may further comprise one or more of dispersing or wetting agent, a suspending agent, and a preservative. Additional excipients, such as fillers and sweetening, flavoring, or coloring agents, may also be included in these formulations.

[0165] A pharmaceutical composition of the invention may also be prepared, packaged, or sold in the form of oil-in-water emulsion or a water-in-oil emulsion. The oily phase may be a vegetable oil such as olive or arachis oil, a mineral oil such as liquid paraffin, or a combination of these. Such compositions may further comprise one or more emulsifying agents such as naturally occurring gums such as gum acacia or gum tragacanth, naturally-occurring phosphatides such as soybean or lecithin phosphatide, esters or partial esters derived from combinations of fatty acids and hexitol anhydrides such as sorbitan monooleate, and condensation products of such partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. These emulsions may also contain additional ingredients including, for example, sweetening or flavoring agents.

[0166] Methods for impregnating or coating a material with a chemical composition are known in the art, and include, but are not limited to methods of depositing or binding a chemical composition onto a surface, methods of incorporating a chemical composition into the structure of a material during the synthesis of the material (i.e., such as with a physiologically degradable material), and methods of absorbing an aqueous or oily solution or suspension into an absorbent material, with or without subsequent drying.

[0167] As used herein, “parenteral administration” of a pharmaceutical composition includes any route of administration characterized by physical breaching of a tissue of a subject and administration of the pharmaceutical composition through the breach in the tissue. Parenteral administration thus includes, but is not limited to, administration of a pharmaceutical composition by injection of the composition, by application of the composition through a surgical incision, by application of the composition through a tissue-penetrating non-surgical wound, and the like. In particular, parenteral administration is contemplated to include, but is not limited to, cutaneous, subcutaneous, intraperitoneal, intravenous, intramuscular, intraci sternal injection, and kidney dialytic infusion techniques.

[0168] Formulations of a pharmaceutical composition suitable for parenteral administration comprise the active ingredient combined with a pharmaceutically acceptable carrier, such as sterile water or sterile isotonic saline. Such formulations may be prepared, packaged, or sold in a form suitable for bolus administration or for continuous administration. Injectable formulations may be prepared, packaged, or sold in unit dosage form, such as in ampules or in multi -dose containers containing a preservative. Formulations for parenteral administration include, but are not limited to, suspensions, solutions, emulsions in oily or aqueous vehicles, pastes, and implantable sustained-release or biodegradable formulations. Such formulations may further comprise one or more additional ingredients including, but not limited to, suspending, stabilizing, or dispersing agents. In some examples of a formulation for parenteral administration, the active ingredient is provided in dry (i.e., powder or granular) form for reconstitution with a suitable vehicle (e.g., sterile pyrogen-free water) prior to parenteral administration of the reconstituted composition.

[0169] The pharmaceutical compositions may be prepared, packaged, or sold in the form of a sterile injectable aqueous or oily suspension or solution. This suspension or solution may be formulated according to the known art, and may comprise, in addition to the active ingredient, additional ingredients such as the dispersing agents, wetting agents, or suspending agents described herein. Such sterile injectable formulations may be prepared using a non-toxic parenterally-acceptable diluent or solvent, such as water or 1,3-butane diol, for example. Other acceptable diluents and solvents include, but are not limited to, Ringer's solution, isotonic sodium chloride solution, and fixed oils such as synthetic mono- or di-glycerides. Other parentally-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form, in a liposomal preparation, or as a component of a biodegradable polymer systems. Compositions for sustained release or implantation may comprise pharmaceutically acceptable polymeric or hydrophobic materials such as an emulsion, an ion exchange resin, a sparingly soluble polymer, or a sparingly soluble salt.

[0170] Formulations suitable for topical administration include, but are not limited to, liquid or semi-liquid preparations such as liniments, lotions, oil-in-water or water-in-oil emulsions such as creams, ointments or pastes, and solutions or suspensions. Topically-administrable formulations may, for example, comprise from about 1% to about 10% (w / w) active ingredient, although the concentration of the active ingredient may be as high as the solubility limit of the active ingredient in the solvent Formulations for topical administration may further comprise one or more of the additional ingredients described herein.

[0171] A pharmaceutical composition of the invention may be prepared, packaged, or sold in a formulation suitable for pulmonary administration via the buccal cavity. Such a formulation may comprise dry particles which comprise the active ingredient and which have a diameter in the range from about 0.5 to about 7 nanometers, and preferably from about 1 to about 6 nanometers. Such compositions are conveniently in the form of dry powders for administration using a device comprising a dry powder reservoir to which a stream of propellant may be directed to disperse the powder or using a self-propelling solvent / powder-dispensing container such as a device comprising the active ingredient dissolved or suspended in a low-boiling propellant in a sealed container. Preferably, such powders comprise particles wherein at least 98% of the particles by weight have a diameter greater than 0.5 nanometers and at least 95% of the particles by number have a diameter less than 7 nanometers. More preferably, at least 95% of the particles by weight have a diameter greater than 1 nanometer and at least 90% of the particles by number have a diameter less than 6 nanometers. Dry powder compositions preferably include a solid fine powder diluent such as sugar and are conveniently provided in a unit dose form.

[0172] Low boiling propellants generally include liquid propellants having a boiling point of below 65 °F at atmospheric pressure. Generally the propellant may constitute 50 to 99.9% (w / w) of the composition, and the active ingredient may constitute 0.1 to 20% (w / w) of the composition. The propellant may further comprise additional ingredients such as a liquid nonionic or solid anionic surfactant or a solid diluent (preferably having a particle size of the same order as particles comprising the active ingredient).

[0173] Pharmaceutical compositions of the invention formulated for pulmonary delivery may also provide the active ingredient in the form of droplets of a solution or suspension. Such formulations may be prepared, packaged, or sold as aqueous or dilute alcoholic solutions or suspensions, optionally sterile, comprising the active ingredient, and may conveniently be administered using any nebulization or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface active agent, or a preservative such as methylhydroxybenzoate. The droplets provided by this route of administration preferably have an average diameter in the range from about 0.1 to about 200 nanometers.

[0174] The formulations described herein as being useful for pulmonary delivery are also useful for intranasal delivery of a pharmaceutical composition of the invention.

[0175] Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle from about 0.2 to 500 micrometers.

[0176] Such a formulation is administered in the manner in which snuff is taken i.e. by rapid inhalation through the nasal passage from a container of the powder held close to the nares. Formulations suitable for nasal administration may, for example, comprise from about as little as 0.1% (w / w) and as much as 100% (w / w) of the active ingredient, and may further comprise one or more of the additional ingredients described herein.

[0177] A pharmaceutical composition of the invention may be prepared, packaged, or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of tablets or lozenges made using conventional methods, and may, for example, contain 0.1 to 20% (w / w) active ingredient, the balance comprising an orally dissolvable or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations suitable for buccal administration may comprise a powder or an aerosolized or atomized solution or suspension comprising the active ingredient. Such powdered, aerosolized, or aerosolized formulations, when dispersed, preferably have an average particle or droplet size in the range from about 0.1 nanometers to about 2000 micrometers, and may further comprise one or more of the additional ingredients described herein. A pharmaceutical composition of the invention may be prepared, packaged, or sold in a formulation suitable for ophthalmic administration. Such formulations may, for example, be in the form of eye drops including, for example, a 0.1-1.0% (w / w) solution or suspension of the active ingredient in an aqueous or oily liquid carrier. Such drops may further comprise buffering agents, salts, or one or more other of the additional ingredients described herein. Other opthalmically-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form or in a liposomal preparation.

[0178] As used herein, “additional ingredients” include, but are not limited to, one or more of the following: excipients; surface active agents; dispersing agents; inert diluents; granulating and disintegrating agents; binding agents; lubricating agents; sweetening agents; flavoring agents; coloring agents; preservatives; physiologically degradable compositions such as gelatin; aqueous vehicles and solvents; oily vehicles and solvents; suspending agents; dispersing or wetting agents; emulsifying agents, demulcents; buffers; salts; thickening agents; fillers; emulsifying agents; antioxidants; antibiotics; antifungal agents; stabilizing agents; and pharmaceutically acceptable polymeric or hydrophobic materials. Other “additional ingredients” which may be included in the pharmaceutical compositions of the invention are known in the art and described, for example in Genaro, ed., 1985, Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa.

[0179] Typically dosages of the compound of the invention which may be administered to an animal or patient, preferably a human, range in amount from about 0.01 mg to about 100 g per kilogram of body weight of the animal or patient. While the precise dosage administered will vary depending upon any number of factors, including, but not limited to, the type of animal and type of disease state being treated, the age of the animal or patient and the route of administration. Preferably, the dosage of the compound will vary from about 0.01 mg to about 500 mg per kilogram of body weight of the animal or patient. The compound can be administered to an animal or patient as frequently as several times daily, or it can be administered less frequently, such as once a day, once a week, once every two weeks, once a month, or even less frequently, such as once every several months or even once a year or less. The frequency of the dose will be readily apparent to the skilled artisan and will depend upon any number of factors, such as, but not limited to, the type and severity of the disease being treated, the type and age of the animal, patient, etc. Administration of the compounds of the present invention or the compositions thereof may be continuous or intermittent, depending, for example, upon the recipient's physiological condition, whether the purpose of the administration is therapeutic or prophylactic, and other factors known to skilled practitioners. The administration of the agents of the invention may be essentially continuous over a preselected period of time or may be in a series of spaced doses. Both local and systemic administration is contemplated. The amount administered will vary depending on various factors including, but not limited to, the composition chosen, the particular disease, the weight, the physical condition, and the age of the mammal, and whether prevention or treatment is to be achieved. Such factors can be readily determined by the clinician employing animal models or other test systems which are well known to the art.

[0180] One or more suitable unit dosage forms having the therapeutic agent(s) of the invention, which, as discussed below, may optionally be formulated for sustained release, can be administered by a variety of routes including parenteral, including by intravenous and intramuscular routes, as well as by direct injection into the diseased tissue. For example, the therapeutic agent may be directly injected into the muscle. The formulations may, where appropriate, be conveniently presented in discrete unit dosage forms and may be prepared by any of the methods well known to pharmacy. Such methods may include the step of bringing into association the therapeutic agent with liquid carriers, solid matrices, semi-solid carriers, finely divided solid carriers or combinations thereof, and then, if necessary, introducing or shaping the product into the desired delivery system.

[0181] When the therapeutic agents of the invention are prepared for administration, they are preferably combined with a pharmaceutically acceptable carrier, diluent or excipient to form a pharmaceutical formulation, or unit dosage form. The total active ingredients in such formulations include from 0.1 to 99.9% by weight of the formulation. A “pharmaceutically acceptable” is a carrier, diluent, excipient, and / or salt that is compatible with the other ingredients of the formulation, and not deleterious to the recipient thereof. The active ingredient for administration may be present as a powder or as granules; as a solution, a suspension or an emulsion.

[0182] Pharmaceutical formulations containing the therapeutic agents of the invention can be prepared by procedures known in the art using well known and readily available ingredients. The therapeutic agents of the invention can also be formulated as solutions appropriate for parenteral administration, for instance by intramuscular, subcutaneous or intravenous routes.

[0183] The pharmaceutical formulations of the therapeutic agents of the invention can also take the form of an aqueous or anhydrous solution or dispersion, or alternatively the form of an emulsion or suspension.

[0184] Thus, the therapeutic agent may be formulated for parenteral administration (e g., by injection, for example, bolus injection or continuous infusion) and may be presented in unit dose form in ampules, pre-filled syringes, small volume infusion containers or in multi-dose containers with an added preservative. The active ingredients may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Alternatively, the active ingredients may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization from solution, for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use.

[0185] It will be appreciated that the unit content of active ingredient or ingredients contained in an individual aerosol dose of each dosage form need not in itself constitute an effective amount for treating the particular indication or disease since the necessary effective amount can be reached by administration of a plurality of dosage units. Moreover, the effective amount may be achieved using less than the dose in the dosage form, either individually, or in a series of administrations.

[0186] The pharmaceutical formulations of the present invention may include, as optional ingredients, pharmaceutically acceptable carriers, diluents, solubilizing or emulsifying agents, and salts of the type that are well-known in the art. Specific non-limiting examples of the carriers and / or diluents that are useful in the pharmaceutical formulations of the present invention include water and physiologically acceptable buffered saline solutions, such as phosphate buffered saline solutions pH 7.0-8.0.

[0187] In general, water, suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration contain the active ingredient, suitable stabilizing agents and, if necessary, buffer substances. Antioxidizing agents such as sodium bisulfate, sodium sulfite or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium Ethylenediaminetetraacetic acid (EDTA). In addition, parenteral solutions can contain preservatives such as benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, a standard reference text in this field.

[0188] The active ingredients of the invention may be formulated to be suspended in a pharmaceutically acceptable composition suitable for use in mammals and in particular, in humans. Such formulations include the use of adjuvants such as muramyl dipeptide derivatives (MDP) or analogs that are described in U.S. Patent Nos. 4,082,735; 4,082,736; 4,101,536; 4,185,089; 4,235,771; and 4,406,890. Other adjuvants, which are useful, include alum (Pierce Chemical Co.), lipid A, trehalose dimycolate and dimethyldioctadecylammonium bromide (DDA), Freund’s adjuvant, and IL-12. Other components may include a polyoxypropylenepolyoxyethylene block polymer (Pluronic®), a non-ionic surfactant, and a metabolizable oil such as squalene (U.S. Patent No. 4,606,918).

[0189] Additionally, standard pharmaceutical methods can be employed to control the duration of action. These are well known in the art and include control release preparations and can include appropriate macromolecules, for example polymers, polyesters, polyamino acids, polyvinyl, pyrolidone, ethylenevinylacetate, methyl cellulose, carboxymethyl cellulose or protamine sulfate. The concentration of macromolecules as well as the methods of incorporation can be adjusted in order to control release. Additionally, the agent can be incorporated into particles of polymeric materials such as polyesters, polyamino acids, hydrogels, poly(lactic acid) or ethylenevinylacetate copolymers. In addition to being incorporated, these agents can also be used to trap the compound in microcapsules.

[0190] Accordingly, the composition of the present invention may be delivered via various routes and to various sites in a mammal body to achieve a particular effect (see, e.g., Rosenfeld et al., 1991; Rosenfeld et al., 1991a; laffe et al., supra; Berkner, supra). One skilled in the art will recognize that although more than one route can be used for administration, a particular route can provide a more immediate and more effective reaction than another route. In some examples, the composition described above is administered to the subject by subretinal injection. In other embodiments, the composition is administered by intravitreal injection. Other forms of administration that may be useful in the methods described herein include, but are not limited to, direct delivery to a desired organ (e.g., the eye), oral, inhalation, intranasal, intratracheal, intravenous, intramuscular, subcutaneous, intradermal, and other parental routes of administration. Additionally, routes of administration may be combined, if desired. In another embodiments, route of administration is subretinal injection or intravitreal injection.

[0191] The active ingredients of the present invention can be provided in unit dosage form wherein each dosage unit, e.g., a teaspoonful, tablet, solution, or suppository, contains a predetermined amount of the composition, alone or in appropriate combination with other active agents. The term “unit dosage form” as used herein refers to physically discrete units suitable as unitary dosages for human and mammal subjects, each unit containing a predetermined quantity of the compositions of the present invention, alone or in combination with other active agents, calculated in an amount sufficient to produce the desired effect, in association with a pharmaceutically acceptable diluent, carrier, or vehicle, where appropriate. The specifications for the unit dosage forms of the present invention depend on the particular effect to be achieved and the particular pharmacodynamics associated with the composition in the particular host.

[0192] These methods described herein are by no means all-inclusive, and further methods to suit the specific application will be apparent to the ordinary skilled artisan. Moreover, the effective amount of the compositions can be further approximated through analogy to compounds known to exert the desired effect.

[0193] It will be understood by those of skill in the art that numerous and various modifications can be made without departing from the spirit of the present disclosure. Therefore, it should be clearly understood that the forms disclosed herein are illustrative only and are not intended to limit the scope of the present disclosure.

[0194] Methods of Making

[0195] Also described herein is a method of synthesizing a polymer comprising the steps of: providing a solution comprising a monomer; adding an initiator to the solution; and polymerizing the monomer to provide a polymer; wherein the monomer is represented by General Formula (II):

[0196] General Formula (II), wherein: X represents 0 or S; ring A represents a C4-C7 cycloalkyl or a C3-C6 heterocycloalkyl; R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or a combination thereof, which can optionally be further substituted; each occurrence of RAindependently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cyaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, or C3-C6 heterocycloalkyl, which can optionally be further substituted; wherein any two adjacent RAcan join to form a ring; and m represents an integer from 1 to 10.

[0197] In some examples, the initiator is represented by General Formula (III):

[0198] General Formula (III) wherein: X represents 0 or S; R and RNeach independently represent a C1-C30 alkyl, Ci- C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C?aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and Y represents a counterion.

[0199] In some examples, the initiator comprises a moiety capable of forming a stable anion, including, but not limited to, a halogen (i.e. iodine, bromine, chlorine, fluorine), tosyl, or triflate. In some examples, the initiator is selected from the group consisting of alkyl iodide, alkyl tosylate, and alkyl triflate, wherein the alkyl group includes alkyls having anywhere from and between 1 to 100 carbons and may be any isomer, for example, 1 (methyl), 2 (ethyl), 3 (propyl), or 4 carbons (n-butyl, isobutyl), etc.. In some examples, the initiator is methyl tosylate, methyl triflate, or methyl iodide. Some or all of the initiator may be covalently linked to the resulting polymer after polymerization or may be modified or cleaved post-polymerization. For example, if methyl tosylate is used as the initiator, a methyl group may be covalently attached to the resulting polymer.

[0200] In some examples, polymerization is performed with a target degree of polymerization. In some examples, the degree of polymerization is about 1 to about 500. In some examples, the degree of polymerization is about 1 to about 10. In some examples, the degree of polymerization is about 10 to about 500. In some examples, the degree of polymerization is about 20 to about 500. In some examples, the degree of polymerization is about 30 to about 500. In some examples, the degree of polymerization is about 40 to about 500. In some examples, the degree of polymerization is about 50 to about 500. In some examples, the degree of polymerization is about 60 to about 500. In some examples, the degree of polymerization is about 70 to about 500. In some examples, the degree of polymerization is about 80 to about 500. In some examples, the degree of polymerization is about 90 to about 500. In some examples, the degree of polymerization is about 100 to about 500. In some examples, the degree of polymerization is about 10 to about 400. In some examples, the degree of polymerization is about 20 to about 400. In some examples, the degree of polymerization is about 30 to about 400. In some examples, the degree of polymerization is about 40 to about 400. In some examples, the degree of polymerization is about 50 to about 400. In some examples, the degree of polymerization is about 60 to about 400. In some examples, the degree of polymerization is about 70 to about 400. In some examples, the degree of polymerization is about 80 to about 400. In some examples, the degree of polymerization is about 90 to about 400. In some examples, the degree of polymerization is about 100 to about 400. In some examples, the degree of polymerization is about 10 to about 300. In some examples, the degree of polymerization is about 20 to about 300. In some examples, the degree of polymerization is about 30 to about 300. In some examples, the degree of polymerization is about 40 to about 300. In some examples, the degree of polymerization is about 50 to about 300. In some examples, the degree of polymerization is about 60 to about 300. In some examples, the degree of polymerization is about 70 to about 300. In some examples, the degree of polymerization is about 80 to about 300. In some examples, the degree of polymerization is about 90 to about 300. In some examples, the degree of polymerization is about 100 to about 300. In some examples, the degree of polymerization is about 50 to about 250. In some examples, the degree of polymerization is about 60 to about 250. In some examples, the degree of polymerization is about 70 to about 250. In some examples, the degree of polymerization is about 80 to about 250. In some examples, the degree of polymerization is about 90 to about 250. In some examples, the degree of polymerization is about 100 to about 250.

[0201] In some examples, the polymerization is performed at about 25 °C to about 100°C. In some examples, the polymerization is performed at about 25 °C to about 90°C. In some examples, the polymerization is performed at about 25 °C to about 80°C. In some examples, the polymerization is performed at about 35°C to about 80°C. In some examples, the polymerization is performed at about 45°C to about 80°C. In some examples, the polymerization is performed at about 55°C to about 80°C. In some examples, the polymerization is performed at about 60°C to about 80°C. In some examples, the polymerization is performed at about 60°C to about 90°C. In some examples, the polymerization is performed at about 60°C to about 100°C

[0202] In some examples, the solution comprises an organic solvent. In some examples, the solution comprises an organic aprotic solvent. Exemplary solvents include, but are not limited to, di chloroethane, dimethylformamide, acetonitrile, acetone, and dichloromethane. In some examples, the solution comprises dichloroethane.

[0203] In some examples, the step of polymerizing the monomer is automated. In some examples, the step of polymerizing the monomer is performed on a stir plate. In some examples, the step of polymerizing the monomer is performed on a hot plate. In some examples, the step of polymerizing the monomer is performed using a heating block.

[0204] In some examples, the solution comprising the monomer has a concentration of monomer of 10 M to 300 M. In some examples, the solution comprising the monomer has a concentration of monomer of 20 M to 300 M. In some examples, the solution comprising the monomer has a concentration of monomer of 30 M to 300 M. In some examples, the solution comprising the monomer has a concentration of monomer of 40 M to 300 M. In some examples, the solution comprising the monomer has a concentration of monomer of 50 M to 300 M. In some examples, the solution comprising the monomer has a concentration of monomer of 60 M to 300 M. In some examples, the solution comprising the monomer has a concentration of monomer of 10 M to 60 M. In some examples, the solution comprising the monomer has a concentration of monomer of 20 M to 60 M. In some examples, the solution comprising the monomer has a concentration of monomer of 30 M to 60 M. In some examples, the solution comprising the monomer has a concentration of monomer of 40 M to 60 M. In some examples, the solution comprising the monomer has a concentration of monomer of 50 M to 60 M. In some examples, the solution comprising the monomer has a concentration of monomer of 10 M to 50 M. In some examples, the solution comprising the monomer has a concentration of monomer of 20 M to 50 M. In some examples, the solution comprising the monomer has a concentration of monomer of 30 M to 50 M. In some examples, the solution comprising the monomer has a concentration of monomer of 40 M to 50 M. In some examples, the solution comprising the monomer has a concentration of about 30 M. In some examples, the solution comprising the monomer has a concentration of about 35 M. In some examples, the solution comprising the monomer has a concentration of about 40 M. In some examples, the solution comprising the monomer has a concentration of about 45 M. In some examples, the solution comprising the monomer has a concentration of about 50 M. In some examples, the solution comprising the monomer has a concentration of about 55 M.

[0205] In some examples, Y represents a counterion selected from the group consisting of tosylate, triflate, halide, borate, and phosphate.

[0206] In some examples, R represents C1-C30 alkyl. In some examples, R represents methyl. In some examples, RNrepresents C1-C30 alkyl. In some examples, RNrepresents methyl. In some examples, Y represents triflate. In some examples, Y is further substituted.

[0207] In some examples, the monomer represented by General Formula (II) is further represented by General Formula (Ila):

[0208] General Formula (Ila), wherein: X represents O or S; R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cv aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, or C3-C6 heterocycloalkyl, which can optionally be further substituted; and each R1, R2, R3, R4, R5, R6, R7, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cvaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, or C3-C6 heterocycloalkyl, which can optionally be further substituted.

[0209] In some examples, at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises C1-C30 alkyl ester. In some examples, at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises an alkyl ester. In some examples, at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises a methyl alkanoate. In some examples, at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises a C5-C?aryl.

[0210] In some examples, the monomer represented by General Formula (II) is further represented by General Formula (lib) : wherein: X represents 0 or S; R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Czaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, or C3-C6 heterocycloalkyl, which can optionally be further substituted; and each R1, R2, R3, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C5-C?aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted. In some examples, at least one of R1, R2, and R3comprises a C5-C7 aryl group. In some examples, at least one of R1, R2, and R3are a combination of a C1-C30 alkyl and a C5-C7 aryl, such as benzyl or homobenzyl. In some examples, at least one of R1, R2, and R3is not represented by acetoxy (OAc).

[0211] In some examples, the monomer represented by General Formula (II) is further represented by General Formula (lie):

[0212] General Formula (lie).

[0213] In some examples, the monomer represented by General Formula (n) is represented by one of the following structures, or a combination thereof:

[0214] In some examples, the polymerization step or the step of polymerizing the monomer is monitored by percent conversion. In some examples, “percent conversion” is defined as the percentage of monomer converted to polymer.

[0215] In some examples, the polymerization is performed using two or more monomers comprising different carbohydrates. In some examples, the polymerization step is performed using a monomer which does not comprise a carbohydrate. The method may also involve a solution comprising a combination of monomers to produce a copolymer that does not have distinct blocks of comonomers. In some examples, the polymerization step is performed on two or more monomers to produce a random copolymer. In some examples, the polymerization step is performed to produce a statistical copolymer. In some examples, the polymerization step is performed on two or more monomers to produce a block copolymer. Thus, in some examples, the method may further comprise the step of reacting the polymer with a comonomer and polymerizing the comonomer as a second block off of the polymer to provide a block copolymer. In some examples, the polymerization step is performed on two or more monomers to produce an alternating copolymer. In some examples, the polymerization step is performed to produce a stereoblock copolymer. In some examples, the polymerization step is performed to produce a gradient copolymer.

[0216] In some examples, a method of polymerization alternative to CROP is used to produce a copolymer of the polymer. Exemplary methods of polymerization include, but are not limited to, atom transfer free radical polymerization (ATRP), reversible addition fragmentation chain transfer (RAFT) polymerization, anionic polymerization, living polymerization, chain shuttling polymerization, free radical polymerization, and nitroxide mediated radical polymerization (NMP).

[0217] In some examples, the polymer is isolated by evaporating solvent. In some examples, the polymer is isolated by filtration. In some examples, the polymer is isolated by precipitation. In some examples, the polymer is isolated using drying. In some examples, the polymer is isolated using dialysis.

[0218] Methods of Use

[0219] The polymers and / or compositions described herein demonstrate uniquely enhanced stability and do not undergo degradation under intense degradation conditions. In some examples, the polymers and / or compositions described herein have enhanced stability towards degradation (i.e. via strong acids, ultrasonic degradation, enzymatic degradation) when compared to natural polysaccharides such as chitosan.

[0220] In some examples, the polymers and / or compositions undergo little to no degradation upon exposure to strong acids such as, but not limited to, acetic acid, hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, hydroiodic acid, perchloric acid, or combinations or solutions thereof, and are stable in acidic conditions for more than 20, 40, 60, 80, or 100 hours.

[0221] The polymer and / or composition described herein can be processed and incorporated into textiles and / or coatings using methods including, but not limited to, weaving and molding. Thus, also described herein are textiles and / or coatings comprising a polymer and / or composition disclosed herein. In some examples, the polymers and / or compositions may be applied as a coating onto a textile or sheet or incorporated as a liquid into a textile or sheet using any method known in the art, including but not limited to, spraying, padding, and / or vapor coating during any step of the textile fabrication process, such as during spinning or sheet fabrication. The polymer and / or composition discussed herein may also be used as an additive in food and may serve as a food stabilizer. Thus, also described herein are food additives comprising the polymer and / or composition, such as food stabilizers that enhance the quality, consistency, texture, structure, etc. of food. In some examples, the polymer and / or composition may perform the function of allowing incompatible or immiscible food ingredients to remain in a homogenous state after mixing; improving the thickness, creaminess, or texture of food products; maintaining the consistency and texture of food products; and combinations thereof.

[0222] In some examples, the polymers and / or compositions can be used to deliver a payload to a cell of interest. In some examples, the polymers and / or compositions of the present invention can be used to deliver a drug to a subject.

[0223] In some examples, the present invention provides a method comprising the step of administering to the subject a composition comprising a polymer described herein.

[0224] Thus, in various embodiments, the present invention provides a method of treating or preventing a disease or disorder associated with immune cell function, immune response, activation of a cell, activation of an immune cell, or any combination thereof in a subject in need thereof. In some examples, the present invention provides a method of treating or preventing a disease or disorder in a subject in need thereof. In some examples, the disease or disorder is a disease or disorder associated with abnormal immune cell function in a subject in need thereof. In some examples, the present invention provides a method of treating or preventing a cancer in a subject in need thereof.

[0225] In some examples, the composition further comprises at least one therapeutic agent as described herein. In some examples, the composition delivers the at least one therapeutic agent to a cell. In some examples, the composition readily releases the at least one therapeutic agent. Exemplary therapeutic agents include, but are not limited to, small molecules, anticancer agents, antibodies, immunomodulatory agents, chelating agents, and imaging agents.

[0226] In some examples, the composition is water-soluble. In some examples, the subject has a disease. In some examples, the subject has cancer. Examples of various cancers include but are not limited to, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, renal cancer, liver cancer, brain cancer, head and neck cancers, lymphoma, leukemia, lung cancer and the like.

[0227] Any therapeutic agent or any combination of therapeutic agents disclosed herein may be administered to a subject to treat a disease or disorder. The therapeutic agents herein can be formulated in any number of ways, often according to various known formulations in the art or as disclosed or referenced herein.

[0228] In certain embodiments, the method of treating a disease or disorder comprises a “triggered” functionality. In other words, the system may remain inert in the body until specifically triggered. In some embodiments, the polymer is used advantageously in therapeutic applications such as to first target the polymer to a specified location, and then trigger them into an activated state. Sometimes referred to as a “dual targeted delivery system,” this feature may minimize the side effects of systemic therapeutic agents. For example, in some embodiments, upon delivering the polymer to a specific cell, a reagent, such as water, proton, acid, or protonated water, may be applied to the cell thereby causing the release of a therapeutic agent from the polymer. In some embodiments, this may provide a clinician the ability to control and visualize drug therapy noninvasively.

[0229] In some embodiments, the size (e.g., average diameter of a polymer assembly) of the compound or composition of the present invention allows for passive diffusion into cells. In some embodiments, where the compound or composition is on a smaller scale, the small size (e.g., average diameter of a polymer assembly) allows the compound or compositions to travel almost anywhere in the body where therapy may need to be performed. For example, in some embodiments, the method comprises compounds that act as a hydrolysis triggered therapeutic agent delivery and therapeutic agent release systems.

[0230] In some examples, the compound or composition undergoes uptake into cells. In some examples, the compound or composition undergoes uptake into cancer cells. In some examples, the compound or composition undergoes uptake into breast cancer cells. In some examples, the compound or composition undergoes uptake into liver cancer cells. In some examples, the compound or composition undergoes uptake into macrophage cells. In some examples, the compound or composition undergoes uptake into dendritic cells. For example, In some examples, the compound or composition can be coated with dextran to target the macrophage cells, since macrophages have dextran receptors. In various embodiments, the method further comprises allowing the compound or composition to accumulate in a region of the biological tissue, wherein the targeting domain facilitated accumulation of the compound, nanoparticle, or composition in the region. In some examples, the compound or composition localizes around the exterior of the nucleus.

[0231] In various aspects, the compound or composition of the present invention can be used alone or in combination with a therapeutic agent to deliver a therapeutic agent payload to a target cell. Often, the therapeutic agent may be released based on the degradation of, e.g., a controlled release biodegradable matrix and / or polymer.

[0232] The preferred dosage of the compound or nanoparticle will vary according to a number of factors, such as the administration route, the age, weight and species of the subject, but in general containing in the order of from 1 pmol / kg to 1 mmol / kg body weight of the compound or nanoparticle.

[0233] Administration may be topical, parenteral (e.g., intravenously, intraarterially, intramuscularly, interstitially, subcutaneously, transdermally, or intrasternally), or into an externally voiding body cavity (e.g., the gastrointestinal tract, rectum, bladder, uterus, vagina, nose, ears or lungs), peritoneally, orally, intradermal, ocular, in an animate human or nonhuman (e.g., mammalian, reptilian or avian) body.

[0234] In certain embodiments, the compound or composition herein is used in conjunction with an anti-cancer agent known in the art. Exemplary anti-cancer agents include, but are not limited to, immunotherapy agents, immunomodulatory agents, antineoplastic agents, chemotherapeutic agents, radioimmunotherapy agents, and monoclonal antibodies.

[0235] In some embodiments, the anti-cancer agent may be a prodrug form of an anti-cancer agent. As used herein, the term “prodrug form” and its derivatives is used to refer to a drug that has been chemically modified to add and / or remove one or more substituents in such a manner that, upon introduction of the prodrug form into a subject, such a modification may be reversed by naturally occurring processes, thus reproducing the drug. The use of a prodrug form of an anti-cancer agent in the compositions, among other things, may increase the concentration of the anti-cancer agent in the compositions of the present disclosure. In certain embodiments, an anticancer agent may be chemically modified with an alkyl or acyl group or some form of lipid. The selection of such a chemical modification, including the substituent(s) to add and / or remove to create the prodrug, may depend upon a number of factors including, but not limited to, the particular drug and the desired properties of the prodrug. One of ordinary skill in the art, with the benefit of this disclosure, will recognize suitable chemical modifications. EMBODIMENTS

[0236] 1. A polymer comprising a structure represented by General Formula (I):

[0237] General Formula (I) wherein:

[0238] X represents 0 or S; ring A represents a C4-C7 cycloalkyl or a C3-C6 heterocycloalkyl;

[0239] R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, or C3-C6 heterocycloalkyl, which can optionally be further substituted; each occurrence of RAindependently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C?aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein any two adjacent RAcan join to form a ring; n represents an integer from 10-500; and m represents an integer from 1 to 10.

[0240] 2. The polymer of embodiment 1, wherein R represents a C1-C30 alkyl which is optionally further substituted.

[0241] 3. The polymer of embodiment 1 or 2, wherein n is 10. 4. The polymer of any one of embodiments 1-3, wherein the polymer comprises General

[0242] Formula (lb):

[0243] General Formula (lb), wherein: each R1, R2, R3, R4, R5, R6, R7, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted.

[0244] 5. The polymer of embodiment 4, wherein at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises a C1-C30 alkyl ester.

[0245] 6. The polymer of any one of embodiments 1-5, wherein ring A is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, metabolites thereof, and any combination thereof.

[0246] 7. The polymer of any one of embodiments 1-6, wherein ring A is selected from the group consisting of galactose, glucose, mannose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, furanose, and any stereochemical isomer thereof.

[0247] 8. The polymer of any one of embodiments 1-7, wherein the polymer is a copolymer comprising a repeat unit of at least two monomers, wherein at least one monomer comprises a monosaccharide. 9. The polymer of any one of embodiments 1-8, wherein the polymer further comprises General Formula (Ic):

[0248] General Formula (Ic), wherein:

[0249] X represents 0 or S;

[0250] R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and each R1, R2, R3, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, Cs-C7aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted.

[0251] 10. The polymer of embodiment 9, wherein at least one of R1, R2, and R3is benzyl.

[0252] 11. The polymer of any one of embodiments 1-10, wherein the polymer comprises at least one of the following structures:

[0253] A nanoparticle or composition comprising the polymer of any one of embodiments 1-11. A membrane or coating comprising the polymer of any one of embodiments 1-12. A method of synthesizing a polymer comprising the steps of providing a solution comprising a monomer; adding an initiator to the solution; and polymerizing the monomer to provide a polymer; wherein the monomer is represented by General Formula (II):

[0254] General Formula (II), wherein:

[0255] X represents 0 or S; ring A represents a C4-C7 cycloalkyl or a C3-C6 heterocycloalkyl;

[0256] R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; each occurrence of RAindependently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-C7aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein any two adjacent RAcan join to form a ring; and m represents an integer from 1 to 10.

[0257] 15. The method of embodiment 14, wherein the initiator is represented by General Formula (III):

[0258] General Formula (III) wherein:

[0259] X represents 0 or S;

[0260] R and RNeach independently represent a C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cyaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and

[0261] Y represents a counterion selected from the group consisting of tosylate, triflate, halide, borate, and phosphate.

[0262] 16. The method of embodiment 14 or 15, wherein the initiator is methyl tosylate.

[0263] 17. The method of any one of embodiments 14-16, wherein the solution comprises an organic solvent. 18. The method of any one of embodiments 14-17, wherein ring A is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, metabolites thereof, and any combination thereof.

[0264] 19. The method of any one of embodiments 14-18, wherein the monomer represented by General Formula (II) is further represented by General Formula (Ila):

[0265] General Formula (Ila), wherein:

[0266] X represents 0 or S;

[0267] R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and each R1, R2, R3, R4, R5, R6, R7, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises a Cs-Cvaryl.

[0268] 20. The method of any one of embodiments 14-19, wherein the monomer represented by General Formula (II) is represented by one of the following structures, or a combination thereof:

[0269]

[0270] EXPERIMENTAL EXAMPLES

[0271] The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.

[0272] Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the present invention and practice the claimed methods. The following working examples therefore are not to be construed as limiting in any way the remainder of the disclosure.

[0273] Example 1 : Polysaccharide Meets Polyoxazoline: A New Frontier in Functional Glycomaterials Polysaccharides play a critical role in numerous applications due to their exceptional ability to regulate water interactions, making them indispensable in hydrogels, lubricants, and coatings. However, their broader utility is often limited by challenges such as enzymatic and chemical degradation of the ether linkages between repeating units, batch variability, and difficulties in controlled polymerization. Traditional polymerization methods frequently result in uncontrolled molecular weights and irregular functionalization, restricting the reproducibility and scalability of polysaccharide-based materials. Recent advances in glycomaterials offer promising solutions to these limitations. Among them, polyoxazolines have emerged as a class of synthetic polymers with tunable properties, excellent biocompatibility, and precise molecular weight control, making them attractive candidates for enhancing polysaccharide-based systems. This work leverages insights from glycosyl oxazolines in carbohydrate chemistry to advance the field of synthetic glycomaterials. This example relates to, in part, a controlled, regioselective, and stereoselective polymerization to afford a new class of polysaccharide consisting of pendant amide linked monosaccharides.

[0274] Polyoxazolines are a class of synthetic polymers that have gained attention for their tunable properties and biocompatibility. They have been widely studied for applications in drug delivery, surface coatings, and biomaterials due to their ability to form well-defined polymer structures with precise molecular weight control (Nemati Mahand et al., 2022, European Polymer Journal, 178, 111484; Glassner et al., 2018, Polymer International, 67, 32). Their versatility and chemical stability make them an attractive option for modifying or enhancing naturally derived polymers.

[0275] By incorporating polyoxazolines with polysaccharides, these challenges can be effectively addressed. Polyoxazolines provide precise control over polysaccharide functionality, while forming pendant amide linkages between monosaccharide units that are potentially more stable than traditional ether bonds. This approach enhances the structural integrity and reliability of polysaccharide-based materials, paving the way for their expanded use in advanced applications. This example explores the synthesis, polymerization, and degradation of poly(acetamido)saccharides, leveraging insights from glycosyl oxazolines in carbohydrate chemistry to advance the field of synthetic glycomaterials.

[0276] Polyoxazolines and polysaccharides inherently share many advantageous properties, including high hydrophilicity, high biocompatibility, non-immunogenicity, non-toxicity, to name a few. Polysaccharides can provide further functionality to polyoxazolines, while polyoxazolines provide the control needed to grow polysaccharide chains. This enormous potential has been identified previously by K. Chiba (Kadokawa et al., 1996, Macromolecular Rapid Communications, 17, 367; Kadokawa et al., 1997, Macromolecules, 30, 8212) and M. Ouchi (Koda et al., 2019, ACS Macro Lett., 8, 1456), in their first forays into this field.

[0277] However, due to the limited research at the intersection of polyoxazoline and polysaccharide chemistry, the few existing studies applying polyoxazoline chemistry to polysaccharides report conflicting results regarding stereoselectivity. Previous work attempting the use of oxazolines is extensive, but sugar polyoxazolines beyond a 6-mer have never been accessed, meaning that all physical properties and applications have never been tested. These studies also exhibit incomplete conversion and provide little insight into polymerization control. To fully harness the potential of poly(acetamido)saccharides as glycomaterials, achieving both controlled polymerization and stereoregularity is essential. The inconsistencies in stereoselectivity and incomplete conversions observed in prior work suggest an underlying mechanistic challenge. This example utilizes a novel and unique approach by investigating the polymerization mechanism to establish a stereoselective, regioselective, and controlled polymerization pathway for poly(acetamido)saccharides.

[0278] Monomer Selection and Synthesis

[0279] Oxazolines typically undergo cationic ring opening polymerization (CROP) via an SN2 mechanism (Verbraeken et al., 2017, European Polymer Journal, 88, 451); however, the presence of a monosaccharide unit at the 4- and 5-positions on the cyclic imino ether introduces the possibility of an SNI pathway. In this case, the resulting carbocation could be stabilized by the ring oxygen, analogous to the formation of an oxocarbenium intermediate in glycosylation reactions (Fig. 1A). This potential shift in the typical oxazoline polymerization mechanism posed a significant challenge, influencing the choice of protecting groups, solvent, temperature, and catalyst.

[0280] To address this, the selected monomers incorporated two distinct protecting groups, each designed to modulate carbocation stability during polymerization (Fig. IB). The acetyl groups at the 3-, 4-, and 6- positions of OAc-GlcOx not only allow for facile removal but also exert a remote electron-withdrawing effect (Frihed et al., 2015, Chem. Rev., 115, 4963), effectively destabilizing any carbocations that may form in an SNI -like process. Conversely, the ether protecting groups on OBn-GlcOx contribute electron density, theoretically stabilizing potential carbocations and increasing the imine nucleophilicity. The benzyl protecting groups also exhibit stability under stringent reaction conditions, ensuring polymerization proceeds without unintended deprotection or degradation. By leveraging these opposing electronic effects, the polymerization pathway was probed by testing polymerizations with several catalysts.

[0281] The OAc-GlcOx monomer exhibited poor reactivity with a variety of catalysts, showing less than 50% conversion, and suggesting that the cationic propagating species is either too unstable, the nucleophilic species too weak, or potentially a combination of both. The OBn- GlcOx monomer exhibited similar reactivity with all tested catalysts, with successful initiation observed for each, but only full conversion observed with methyl tosylate (MeOTs) (Fig. 2). Ultimately, methyl tosylate was selected for this reason, and because the polymers formed with this catalyst exhibited lower dispersity in test reactions (Table 1) - indicating a faster initiation and potential for a strong alignment with first-order kinetics.

[0282] Table 1. Dispersity associated with the test catalyst reactions using OBn-GlcOx monomer.

[0283] Further optimization of polymerizations involved examining the effects of solvent on the reaction pathway. Oxazoline polymerizations are thermodynamically driven due to unfavourable entropic demands. While propagation is spontaneous due to the isomerization of the cyclic imino ether into a more stable tertiary amide, initiation requires a high temperature and therefore requires a solvent with a relatively high boiling point.

[0284] Solvent has a significant effect on the mechanism in glycosylation reactions (Dorst et al., 2024, Carbohydrate Research, 535, 109010). Three solvents were therefore tested to probe the potential for SNI- and S\2-type mechanisms in the polymerization. Acetonitrile (MeCN) and dimethylformamide (DMF) were tested as polymerization solvents, with the hypothesis that their abilities to stabilize carbocation intermediates in glycosylation reactions through direct interaction with glycosyl cations in the form of nitrile and imidinium ions, respectively, would translate to an SNI polymerization pathway. 1,2-Dichloroethane (DCE) was selected to facilitate a potential SN2 mechanism, given its similarity to dichloromethane which does not directly participate in glycosylations, unlike MeCN and DMF. Additionally, studies with trichloroethylene in glycosylation reactions have shown a strong bias toward SN2 products (Kendale et al., 2014, Organic Letters, 16, 3684), leading to the hypothesis that DCE would interact with the reactive species in a similar manner. Crucially, all three solvents, with their high boiling points, are compatible with the elevated temperatures required for thermodynamically driven polymerizations.

[0285] Interestingly, DCE vastly outcompeted MeCN and DMF as a polymerization solvent, showing full conversion in the same amount of time (Fig. 3). In glycosylation reactions, the MeCN and DMF intermediates, as observed through variable temperature NMR, prefer an a- arrangement as they stabilize the sugar unit from the bottom face. Thus, from this data only, it was still unclear whether the cyclic imino ether is not opening after initiation and is following an SN2-like mechanism, and participating solvents have no effect for this reason, or if anchimeric assistance from the tertiary amide formed through an SNI mechanism is outcompeting any solvent effects.

[0286] With the optimized conditions, the control that the oxazoline moiety seemed to impart towards unnatural polysaccharide was investigated through examination of the kinetics, dispersity, and livingness of the polymerizations. Test reactions targeted a degree of polymerization of 10.

[0287] Polymerizations showed consistently low dispersities as monomer converts to polymer, and can be seen to follow first-order kinetics (Fig. 4), indicating a well-controlled polymerization that results in reproducible, defined polymers.

[0288] This polymerization is regioselective for the 1,2 linkage, as well as stereoselective. Full conversion, monitored by the disappearance of the monomer anomeric proton, is observed after 6 hours. 2D NMR analysis shows that only P-linkages are formed, as the single anomeric proton has a coupling constant of around 7.47Hz. This is further confirmation that the mechanism follows an SN2-like mechanism, as stereoselectivity is impossible if an oxocarbenium intermediate is forming during the polymerization. NMR end group analysis was carried out using isopropanol (IP A) as a terminating agent, as the 6 equivalent protons make it easy to integrate even as the degree of polymerization increases.

[0289] Interestingly, it appeared that the IPA end group terminates in both the a- and conformations. Isopropanol is a very weak nucleophile, and weak nucleophiles like water have been shown to terminate at the 2-position (Nuyken et al., 1996, Macromolecular Chemistry and Physics, 197, 83). However, HMBC analysis showed isopropanol groups terminating at the anomeric position (Fig. 5) indicating that this weak nucleophile is causing more of an SNI mechanism involving a carbocation intermediate.

[0290] Copolymerization with 2-methyl-2-oxazoline: poly(OBn-GlcOx)-block-poly(MeOx)

[0291] Upon determining that the polymerization is controlled, further work was undertaken to determine the livingness of the polymerization. Block copolymerization was carried out with 2- methyl-2-oxazoline (MeOx) to investigate the livingness of the OBn-GlcOx chain ends, as the propagating chain ends should remain reactive indefinitely without termination. As the polymerizations are complete in 6 hours, the reaction was held at 75°C for a further 18 hours, at which point MeOx was added to furnish the second block of the copolymer. Conversion of the second block of the copolymer does not reach 100%, as can be seen in Fig. 6, but dispersities remained lower than 2. Injecting the MeOx monomer after full conversion of the first poly(GlcOx) block involved breaking the polymer ampoule sealed under vacuum, it was hypothesized that the brief introduction of air and water caused the incomplete conversion of the second poly(MeOx) block.

[0292] Degradation

[0293] In order to compare the susceptibility of the pendant amide glycosidic linkages to acid degradation versus typical ether linkages, OBn-GlcOx homopolymers were then subjected to intense acid degradation conditions. Chitosan comes from nature’s second most abundant polysaccharide (Zhou et al., 2022, ACS Applied Materials & Interfaces, 14, 46980) and consists of repeating glucosamine units, differing in the linkages between repeating units. Chitosan contains P-1,4 ether linkages between repeating units, while the inventive homopolymers contain P-1,2 pendant amide linkages.

[0294] Chitosan is an unstable polysaccharide, with its ether linkages susceptible to acidic, ultrasonic, and enzymatic degradation. The preferred method of degradation is typically acidic chemical degradation, and chitosan has been shown to degrade 3.95% in 3% acetic acid over 96 hours. To test the robustness of poly(OBn-GlcOx), the intensity of degradation conditions was increased and the homopolymers were subjected to 50% acetic acid over the course of 96 hours (Fig. 7). The polymers were subjected to solutions of 50% acetic acid, and showed no significant degradation over 96 hours, indicating a much more stable linkage between repeating units.

[0295] Conclusions

[0296] This example applies polyoxazoline chemistry to polysaccharide synthesis and merges their respective control and functionalities. This work demonstrates a controlled, potentially living polymerization that is both regioselective and stereoselective. Using conditions that bias an Sx2-like polyoxazoline mechanism, instead of choosing conditions for a more Sxl-like glycosylation mechanism, allows this polymerization to occur in a regioselective and stereoselective manner. Most notably, the strength of the nucleophile plays an important role in the stereoselectivity - increasing electron density through the use of aryl ether protecting groups biased -selectivity, while weaker nucleophiles like isopropanol showed a mixture of a / p stereoisomers.

[0297] The materials and methods used in the experiments herein will now be described.

[0298] Materials

[0299] All reagents were of the highest commercial quality and used as received without further purification. Anhydrous di chloromethane (DCM) was obtained from distillation of HPLC grade DCM. Acetonitrile and N,N-dimethylformamide were obtained from an HPLC grade solvent push still. Anhydrous 1,2-di chloroethane (DCE), pyridine, benzyl bromide, methyl trifluoromethanesulfonate, methyl -toluenesulfonate, 2-methyl-2-oxazoline, sodium hydride (60% dispersion in mineral oil), methyl iodide, tin (IV) chloride, acetic acid, triethylamine, calcium hydride were obtained from Sigma-Aldrich. Methanol, Dowex 50W X8 Ion Exchange resin were obtained from Supelco. Acetic anhydride was obtained from Oakwood chemical. Glucosamine hydrochloride, 4-dimethylaminopyridine were obtained from Ambeed. Silica flash column chromatography was performed using silica gel (40-63 qm), which was supplied from Sorb tech.

[0300] General methods, instrumentation and measurements

[0301] Synthetic manipulations that required an inert atmosphere (where noted) were carried out under nitrogen using standard Schlenk techniques. NMR ( 1 H, 13C) spectra were recorded on Bruker Prodigy 500 MHz, Bruker 500MHz UltraShield, and Broker Advance Neo 400 MHz spectrometers. The1H, and13C chemical shifts were reported as 8 in units of parts per million (ppm), referenced to the residual solvent. Splitting patterns are denoted as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br (broad). Electrospray ionization (ESI) mass spectra were obtained at the mass spectrometry facility (the University of Texas at Austin). GPC data was measured by using TOSOH EcoSEC Elite HLC-8420GPC.

[0302] Monomer Synthesis

[0303] Synthesis of compound OAc-GlcOx (Tsai et al., 2013, Journal of Materials Chemistry,

[0304] 1, 819).

[0305]

[0306] Scheme 1. Synthetic scheme for compounds OAc-GlcNAc and OAc-GlcOx, reagents and conditions, (a) acetic anhydride, pyridine, 4-dimethylaminopyridine, 24 h, 96%. (b) dichloromethane, tin (IV) chloride, reflux, 48 h.

[0307] Compound OAc-GlcNAc. To a stirred suspension solution of D-glucosamine hydrochloride (12.11 g, 67.6 mmol) in pyridine (100 mL) and acetic anhydride (100 mL), was added 4-dimethylaminopyridine (0.5 g, 4.1 mmol) at room temperature. The resulting cloudy white solution was stirred overnight to a translucent pale yellow. After completion, the solution was co-evaporated with toluene under reduced pressure, then diluted with DCM and successively washed with 2M HC1, saturated aqueous NaHCCh solution, and brine. The organic layer was dried over Na SO4 and concentrated under reduced pressure without further purification to give white powder OAc-GlcNAc (25.39 g, 97%). (500 MHz, CDCh) (X-isomer: 5 = 6.16 (d, J= 3.6 Hz, 1H), 5.61 (d, J= 9.1 Hz, 1H), 5.32 - 5.10 (m, 2H), 4.47 (ddd, J= 10.3, 8.9, 3.5 Hz, 1H), 4.24 (dd, J= 12.5, 4.1 Hz, 1H), 4.05 (dd, J= 12.4, 2.4 Hz, 1H), 4.01 - 3.94 (m, 1H), 2.18 (s, 3H), 2.08 (s, 3H), 2.04 (s, 3H), 2.04 (s, 3H), 1.93 (s, 3H); p-isomer: 5 = 5.68 (d, J= 8.9 Hz, 1H), 5.42 - 5.32 (m, 1H), 5.15 - 5.05 (m, 2H), 4.55 - 4.46 (m, 1H), 4.32 - 4.28 (m, 1H), 4.11 (dd, J= 12.6, 2.3 Hz, 1H), 3.86 - 3.68 (m, 1H), 2.12 (s, 3H), 2.09 (s, 3H), 2.04 (s, 6H), 1.93 (s, 3H).13C NMR (126 MHz, CDCh) 6 171.75 (C), 171.13 (C), 170.73 (C), 170.14 (C), 169.97 (C), 169.56 (C), 169.24 (C), 169.11(C), 168.66 (C), 92.60 (CH), 90.69 (CH), 72.90 (CH), 72.58 (CH), 70.66 (CH), 69.71 (CH), 67.64 (CH), 67.45 (CH), 61.61 (CH2), , 61.52 (CH), 53.00 (CH), 51.04 (CH), 23.20 (CH3), 23.07 (CH3), 20.91 (CH3), 20.71 (CH3), 20.64 (CH3), 20.58 (CH3); LCMS-ESI: m / z calcd. for C16H23NO10, [M + NH4]+407.16, found 407.2. Compound OAc-GlcOx To a stirred solution of dry DCM (250 mL), was added OAc- GlcNAc (12.7 g, 32.6 mmol) under an inert atmosphere. The reaction mixture was cooled to 0°C in an ice bath, then tin (IV) chloride (4 mL, 34.3 mmol) was added dropwise. The resulting mixture was warmed to room temperature, then fitted with a reflux condenser under inert atmosphere, and heated at 50°C for 48 hours. Upon completion by TLC, the reaction was diluted with dry DCM, then quenched slowly with saturated aqueous NaHCCh solution at 0°C. The separated aqueous layer was extracted three times with DCM, then the combined organic layers were washed with brine, dried over Na2SC>4, and concentrated under reduced pressure. The crude orange oil was purified by flash column chromatography on silica gel from 500: 1 DCM: MeOH to 100: 1 DCM: MeOH as the mobile phase, to afford OAc-GlcOx (10.9 g, 52%) as a pale yellow oil. 'H NMR (500 MHz, CDCh): 5 5.94 (d, J= 7.4 Hz, 1H), 5.23 (t, J= 2.4 Hz, 1H), 4.90 (dd, J= 9.3, 0.9 Hz, 1H), 4.14 (dd, J= 4.2, 1.6 Hz, 2H), 4.12 - 4.09 (m, 1H), 3.57 (ddd, 8.9, 5.0, 3.7 Hz, 1H), 2.09, 2.07, 2.06, 2.05 (each s, 12H);13C NMR (126 MHz, CDCh) :8 170.63 (C), 169.57 (C), 169.25 (C), 166.76 (C), 99.39 (CH), 70.30 (CH), 68.33 (CH), 67.49 (CH), 64.86 (CH), 63.32 (CH2), 20.92 (CH3), 20.85 (CH3), 20.76 (CH3), 13.96 (CH3); LCMS-ESI: m / z calcd. for C14H19NO8, [M + H]+330.11, found 330.1.

[0308] Synthesis of compound OBn-GlcOx

[0309] Scheme 2. Synthetic scheme for compounds OH-GlcOx and OBn-GlcOx, reagents and conditions, (a) methanol, sodium methoxide, r.t., 2 h. (b) N,N-dimethylformamide, sodium hydride, benzyl bromide, r.t., 24 h.

[0310] Compound OH-GlcOx (Paiotta et al., 2018, European Journal of Organic Chemistry, 2018, 1946). Compound OAc-GlcOx (4.86 g, 14.8 mmol) dissolved in dry methanol (150 mL) under inert atmosphere. NaOMe (5.17 g, 95.7 mmol, 6.5 eq.) was added, and the mixture was stirred for 2 hours at room temperature. Upon completion, the reaction mixture was neutralized with Dowex 50W X8 Ion Exchange resin to pH 7, filtered, and rotovapped to give crude OH- GlcOx, which was used without further purification (2.99 g, quantitative) .1H NMR (500 MHz, D2O) 5 6.00 (d, J= 7.3 Hz, 1H), 4.04 (dq, J= 5.5, 1.8 Hz, 1H), 3.89 (t, J= 3.5 Hz, 1H), 3.83 - 3.81 (m, 1H), 3.71 (d, J= 2.7 Hz, 1H), 3.70 - 3.68 (m, 1H), 3.56 (d, J= 2.3 Hz, OH), 1.96 (s, 3H)13C NMR (126 MHz, D2O) 5 170.59, 102.92, 74.16, 72.43, 71.18, 68.31, 64.20, 59.56, 15.50 ppm; LCMS-ESI: m / z calcd. for CsHnNOs, [M+2K+H]+279.08, found 279.1.

[0311] Compound OBn-GlcOx. Compound OH-GlcOx (756.2 mg, 3.73 mmol) was dissolved in dry DMF (30 mL) with 3A molecular sieves, then cooled to 0°C in an ice bath under an inert atmosphere. Sodium hydride (4 g, 22.1 mmol) was added carefully, and stirred for 45 minutes until bubbling ceased. Benzyl bromide (2 mL, 16.8 mmol) was added dropwise, and the reaction allowed to warm to room temperature. Upon completion after 48 hours, the reaction was cooled to 0°C, quenched with triethylamine, diluted with EtOAc and water, and filtered. The filtrate was extracted twice with EtOAc, washed with brine, dried over Na SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel from 100% DCM: MeOH to 100:1 DCM: MeOH as the mobile phase to afford OBn-GlcOx as a very pale yellow oil (725.7 mg, 41%). 'H NMR (500 MHz, CDCh) (Liu, 2022, Journal of the American Chemical Society, 124, 9789) 5 7.37 - 7.23 (m, 13H), 7.16 (dd, J= 7.2, 2.3 Hz, 2H), 6.02 (d, .7= 7.4 Hz, 1H), 4.69 (d, 12.0 Hz, 1H), 4.59 (d, J= 11.8 Hz, 1H), 4.55 - 4.48 (m,

[0312] 3H), 4.28 (d, J= 11.7 Hz, 1H), 4.21 (dq, <7= 5.9, 1.6 Hz, 1H), 3.99 (t, J= 2.8 Hz, 1H), 3.66 (ddd, <7= 8.9, 2.7, 1.2 Hz, 1H), 3.59 (dd, J= 10.7, 2.3 Hz, 1H), 3.54 (d, .7= 4.8 Hz, 1H), 3.52 - 3.42 (m, 1H), 2.04 (d, J= 1.8 Hz, 3H);13C NMR (126 MHz, CDCh) 6 165.88 (C), 138.07 (Ph), 137.86 (Ph), 137,74 (Ph), 128.51 (Ph), 128.35 (Ph), 128.17 (Ph), 127.99 (Ph), 127.92 (Ph), 127.83 (Ph), 127.62 (Ph), 100.48 (CH), 77.0 (Ph), 75.04 (CH), 73.37 (CH), 72.01 (CH), 71.47 (CH), 70.41 (CH), 69.55 (CH2), 65.80 (CH), 14.14 (CEE); LCMS-ESI: m / z calcd. for C29H31NO5, [M + H]+474.22, found 474.2.

[0313] General polymerization procedure

[0314] Freshly dried DCE was prepared by distillation from CaH2 onto activated 3 A molecular sieves. Catalyst was dissolved in DCE to make a stock solution. Monomer was then dissolved in DCE, and injected into the polymer ampoule under an inert atmosphere. The reaction mixture in the ampoule and the stock solution was then degassed via three freeze-pump-thaw cycles using a dry ice / acetone bath and high vacuum. Catalyst stock solution was thawed, and injected into the tube containing the frozen monomer solution, then the ampoule was sealed under vacuum. The mixture was thawed in water, quickly inverted to introduce catalyst and monomer, then immediately placed into an oil bath at 75°C. After completion, the ampoule was broken open, and the polymerization was quenched with 2-propanol to introduce the moiety used for end group analysis of polymers.

[0315] Block copolymerization procedure

[0316] Followed the general polymerization procedure to prepare the first block of the copolymer. After 24 hours, the polymer solution was frozen, the ampoule broken open, and the second monomer added. The polymer ampoule was placed back under vacuum and sealed, then thawed, inverted, and immediately placed back into the oil bath at 75°C. After the second block of the copolymer was complete, polymerization was quenched with 2-propanol.

[0317] Polymerization Kinetics

[0318] Kinetics was monitored through the shift of the anomeric proton peak inrH NMR from 6.02 ppm to 4.92 ppm, and through integration of the a- and [3-isopropanol end groups.

[0319] Confirmation of anomeric peak- the anomeric proton shifts from 6.02 ppm to 4.92 ppm throughout the polymerization. HSQC shows that the doublet at 4.92 ppm corresponds with the anomeric carbon at 98 ppm (the most downfield sugar ring carbon). There was only one anomeric proton present, with a coupling constant of 7.94 Hz, indicating only P-1 inkages between repeating glucosamine units.

[0320] Confirmation of isopropanol end group - the 6 protons on the two methyl groups on pure isopropanol show up as a singlet at 1.21 ppm in CDCb (Babij et al., 2016, Organic Process Research and Development, 20, 661). Two sets of doublets were observed at 1.14 ppm and 1.05 ppm. While this seemed immediately indicative of a mixture of a and isomers, further experiments were conducted to ensure that the isopropanol was not reacting with the 2-position.

[0321] HMBC analysis of the highlighted proton showed a long-range coupling with the anomeric carbon at 98 ppm, and no long range coupling to the carbonyl carbon at 170 ppm. Furthermore, full disappearance of anomeric monomer proton at 6.02 ppm was observed, which would not be the case if the isopropanol was terminating at the 2-position.

[0322] End group analysis was made somewhat difficult by the broad singlet at 1.19 ppm, but was carried out by integrating the doublet at 1.05 ppm to 6H (2 x CH3 groups on IP A). A sample calculation of the degree of polymerization based on end group integration of the sample below taken at 180 minutes (target DP = 10), is as follows:

[0323] 25.38 + 6 - - - x 2.26 = 11.8

[0324] 6

[0325] Block copolymerization kinetics

[0326] Target degrees of polymerization for poly(OBn-GlcOx)-Woc&-poly(MeOx) was 10 and 50, respectively. CH2 peaks and CH3 peaks (highlighted purple and blue, respectively) in the poly-MeOx block of the copolymer, were first identified upon comparison to homo-poly(MeOx) (Konradi et al., 2008, Langmuir, 24, 613), then confirmed through the use of HSQC.

[0327] End group analysis was first carried out to confirm conversion of the first poly(OBn- GlcOx) block to a target DP of 10. Once this was completed, the anomeric peak at 4.92 ppm was set to 10, and the MeOx CH2 peaks at 3.83 ppm were integrated, and divided by 4 as they corresponded to 4 protons, to give the degree of polymerization. This was compared to the methyl 3H multiplet at 1.81 ppm, to confirm that the degree of polymerization was correct. The following example integration is from a sample that was taken at 15 minutes (target DP = 50) :

[0328] Integrated multiplet at 3.83 ppm 61.79 l 15.44

[0329] Integrated multiplet at 1.81 ppm 47.78

[0330] D l i i 15.92

[0331] The degree of polymerization between the two differs by less than 1 for all samples, so the data presented uses the integration ratio for the peak at 3.83 ppm. Degradation studies

[0332] General degradation procedure

[0333] Polymers were dissolved in a 50:50 v:v solution of methanol and acetic acid to give a concentration of 5 mg / mL. Aliquots were taken at different time points and frozen in a dry ice bath to stop degradation, then the solvents were removed through high vacuum with an acid neutralizing trap to leave the polymer salts.

[0334] NMR comparison of the anomeric proton integration before and after acidic treatment allowed for monitoring of degradation.

[0335] All data points, unless otherwise stated, were performed in triplicate. As the polymerizations were run in sealed ampoules, at each time point three ampoules were broken open and quenched to provide the necessary kinetic data.

[0336] Example 2: Synthesis of Unnatural Polysaccharides

[0337] Unlike glycans isolated from nature, the easy synthesis of these monomers allows for full control over the polymer’s features. The monomers require only a two-step synthesis from the starting glucosamine, with relatively little purification before polymerization required. The monomer itself is stable and does not self-polymerize or degrade easily, making industrial scale up feasible. Stable glycosyl oxazoline monomers were synthesized from carbohydrate starting materials (Fig. 8) and can be polymerized using cationic ring-opening polymerization (CROP) (Fig. 9). Screening conditions for the formation of the galactose oxazoline monomer found the optimized conditions to be in 7 eq. SnCh refluxed at 60°C for 24 hours (Fig. 10).

[0338] The catalyst and solvent were then screened and showed MeOxOTf as the optimal initiator and di chloroethane (DCE) as the optimal solvent (Fig. 11). Monomer concentration was also shown to have an effect on polymer length (Fig. 12). Additional monomers of interest include glucose, galactose, and mannose derivatives (Fig. 13) to probe the effect of monomer structure and stereochemistry on glass transition temperature (Tg), solubility, degradation, and effects of acetyl deprotection.

[0339] Ultimately, a monomer of pendant amide linked glucose acetate monomers can be successfully polymerized with control over degree of polymerization (DP) and low dispersity, showing that these polymerizations are feasible and allow for design control from the start, as opposed to cellulose acetate isolation. Polymer properties and higher molecular weights will be targeted.

[0340] Previous findings that demonstrated the enzymatic resistance of similar oligosaccharides with 1,2-pendant amide linkages (Ouchi et al., 2019, ACS Macro Lett., 8) suggest that the present polysaccharides with the same linkage nature hold promise for intriguing biotechnical applications. Similar properties could offer valuable insights into developing biotechnical agents with enhanced resilience and functionality. Polysaccharides like xanthan gum are also commonly employed as food stabilizers and thickeners. Given the structural similarities and potential properties of the instant polymers, they may find utility as alternative or complementary food gums, contributing to the formulation of stable and textured food products.

[0341] The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations.

Claims

CLAIMSWhat is claimed is:

1. A polymer comprising a structure represented by General Formula (I):General Formula (I) wherein:X represents 0 or S; ring A represents a C4-C7 cycloalkyl or a C3-C6 heterocycloalkyl;R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, or C3-C6 heterocycloalkyl, which can optionally be further substituted; each occurrence of RAindependently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Czaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein any two adjacent RAcan join to form a ring; n represents an integer from 10-500; and m represents an integer from 1 to 10.

2. The polymer of claim 1, wherein R represents a C1-C30 alkyl which is optionally further substituted.

3. The polymer of claim 1, wherein n is 10.

4. The polymer of claim 1, wherein the polymer comprises General Formula (lb):General Formula (lb), wherein: each R1, R2, R3, R4, R5, R6, R7, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted.

5. The polymer of claim 4, wherein at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises a C1-C30 alkyl ester.

6. The polymer of claim 1, wherein ring A is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, metabolites thereof, and any combination thereof.

7. The polymer of claim 1, wherein ring A is selected from the group consisting of galactose, glucose, mannose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, furanose, and any stereochemical isomer thereof.

8. The polymer of claim 1, wherein the polymer is a copolymer comprising a repeat unit of at least two monomers, wherein at least one monomer comprises a monosaccharide.

9. The polymer of claim 1, wherein the polymer further comprises General Formula (Ic):General Formula (Ic), wherein:X represents 0 or S;R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and each R1, R2, R3, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, Cs-C7aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted.

10. The polymer of claim 9, wherein at least one of R1, R2, and R3is benzyl.

11. The polymer of claim 1, wherein the polymer comprises at least one of the following structures:

12. A nanoparticle or composition comprising the polymer of claim 1.

13. A membrane or coating comprising the polymer of claim 1.

14. A method of synthesizing a polymer comprising the steps of: providing a solution comprising a monomer; adding an initiator to the solution; and polymerizing the monomer to provide a polymer; wherein the monomer is represented by General Formula (II):General Formula (II), wherein:X represents 0 or S;ring A represents a C4-C7 cycloalkyl or a C3-C6 heterocycloalkyl;R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; each occurrence of RAindependently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-Cvaryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein any two adjacent RAcan join to form a ring; and m represents an integer from 1 to 10.

15. The method of claim 14, wherein the initiator is represented by General Formula (III):General Formula (III) wherein:X represents 0 or S;R and R each independently represent a C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, Cs-C aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; andY represents a counterion selected from the group consisting of tosylate, triflate, halide, borate, and phosphate.

16. The method of claim 14, wherein the initiator is methyl tosylate.

17. The method of claim 14, wherein the solution comprises an organic solvent.

18. The method of claim 14, wherein ring A is selected from the group consisting of a monosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, any stereochemical isomer thereof, metabolites thereof, and any combination thereof.

19. The method of claim 14, wherein the monomer represented by General Formula (II) is further represented by General Formula (Ila):General Formula (Ila), wherein:X represents 0 or S;R represents C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; and each R1, R2, R3, R4, R5, R6, R7, and R8independently represents a substituent selected from the group consisting of hydrogen, deuterium, halide, hydroxy, C1-C30 alkanoate, C1-C30 alkyl ester, C1-C30 alkoxycarbonyl, C1-C30 alkyl, C1-C30 heteroalkyl, C1-C30 alkyl halide, C1-C30 alkoxy, C5-C7 aryl, C4-C7 heteroaryl, C4-C7 cycloalkyl, C3-C6 heterocycloalkyl, or combinations thereof, which can optionally be further substituted; wherein at least one of R1, R2, R3, R4, R5, R6, R7, and R8comprises a C5-C7 aryl.

20. The method of claim 14, wherein the monomer represented by General Formula (II) is represented by one of the following structures, or a combination thereof:

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