Compounds including a water-solubilization motif and methods of use thereof

Abstract

Described herein are compounds that include a tetrapyrrole macrocycle and a water solubilizing group that is attached to the tetrapyrrole macrocycle along with methods of using the same.

Description

[0001]Attorney Docket No.5051.1014.WO COMPOUNDS INCLUDING A WATER-SOLUBILIZATION MOTIF AND METHODS OF USE THEREOF STATEMENT OF PRIORITY This application claims the benefit of and priority to U.S. Provisional Application Serial Number 63 / 511,202, filed June 30, 2023, the contents of which are hereby incorporated by reference as if recited in full herein. GOVERNMENT SUPPORT This invention was made with government support under grant number 2136700 awarded by the National Science Foundation. The government has certain rights in the invention. FIELD The present invention concerns compounds that include a water-solubilization motif and methods of use thereof. BACKGROUND Therapeutic agents can be hydrophobic, which can create issues with their use such as in regard to renal clearance of the therapeutic agent following administration to a subject. For example, a key issue in cancer therapy is renal clearance of unbound radionuclides. Accordingly new compounds and methods are desired. SUMMARY One aspect of the present invention is directed to a compound comprising a tetrapyrrole macrocycle and a water solubilizing group that is attached to the tetrapyrrole macrocycle, wherein the water solubilizing group comprises a hydroxyl, carboxylic acid, and / or a methoxy group. A further aspect of the present invention is directed to a method of diagnosing a disease or disorder in a subject, the method comprising: administering a compound of the present invention to the subject, thereby diagnosing the disease or disorder in the subject. 1   Attorney Docket No.5051.1014.WO Another aspect of the present invention is directed to a method of treating a subject in need thereof, the method comprising: administering a compound of the present invention to the subject, thereby treating the subject. It is noted that aspects of the invention described with respect to one embodiment, may be incorporated in a different embodiment although not specifically described relative thereto. That is, all embodiments and / or features of any embodiment can be combined in any way and / or combination. Applicant reserves the right to change any originally filed claim and / or file any new claim accordingly, including the right to be able to amend any originally filed claim to depend from and / or incorporate any feature of any other claim or claims although not originally claimed in that manner. These and other objects and / or aspects of the present invention are explained in detail in the specification set forth below. Further features, advantages and details of the present invention will be appreciated by those of ordinary skill in the art from a reading of the figures and the detailed description of the preferred embodiments that follow, such description being merely illustrative of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS Fig.1 shows1H NMR spectra in CDCl3at room temperature of zinc porphyrins Zn2 (top panel) and Zn6 (bottom panel). Peak assignments: (a) The resonance of the triazolyl–H; (b) The resonance of the protons of the –OCH2– linking the meso-aryl and triazole moieties. All other peaks derive from the PEG chains. Fig.2 depicts the crystal structure of compound Zn5 (crystallized from THF at –20 °C). Disorder is omitted for clarity. Fig.3 is a graph showing the absorption spectra of compound 6 in PBS at room temperature. Fig.4 is a graph showing the absorption spectra of compound Cu6 in PBS at room temperature. Fig.5 is a graph showing the absorption spectra of compound 8 in PBS at room temperature. Fig.6 is a graph showing the absorption spectra of compound 11 in PBS at room temperature. 2   Attorney Docket No.5051.1014.WO Fig.7 depicts the wide conformational motion available in the 3,5-disubstituted aryl porphyrin (top panel) versus limited motion for the 2,6-disubstituted aryl porphyrin (bottom panel). DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS The present invention is now described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather these embodiments are provided so that this disclosure will be thorough and complete and will fully convey the scope of the invention to those skilled in the art. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used in the description of the invention and the appended claims, the singular forms "a," "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Unless otherwise defined, all terms (including 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. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the present application and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. In case of a conflict in terminology, the present specification is controlling. Also as used herein, "and / or" refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative ("or"). Unless the context indicates otherwise, it is specifically intended that the various features of the invention described herein can be used in any combination. Moreover, the present invention 3   Attorney Docket No.5051.1014.WO also contemplates that in some embodiments of the invention, any feature or combination of features set forth herein can be excluded or omitted. To illustrate, if the specification states that a complex comprises components A, B and C, it is specifically intended that any of A, B or C, or a combination thereof, can be omitted and disclaimed. As used herein, the transitional phrase "consisting essentially of" (and grammatical variants) is to be interpreted as encompassing the recited materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention. See, In re Herz, 537 F.2d 549, 551-52, 190 U.S.P.Q. 461, 463 (CCPA 1976) (emphasis in the original); see also MPEP § 2111.03. Thus, the term "consisting essentially of" as used herein should not be interpreted as equivalent to "comprising." It will also be understood that, as used herein, the terms "example," "exemplary," and grammatical variations thereof are intended to refer to non-limiting examples and / or variant embodiments discussed herein, and are not intended to indicate preference for one or more embodiments discussed herein compared to one or more other embodiments. The term "about," as used herein when referring to a measurable value such as an amount or concentration and the like, is meant to encompass variations of ± 10%, ± 5%, ± 1%, ± 0.5%, or even ± 0.1% of the specified value as well as the specified value. For example, "about X" where X is the measurable value, is meant to include X as well as variations of ± 10%, ± 5%, ± 1%, ± 0.5%, or even ± 0.1% of X. A range provided herein for a measurable value may include any other range and / or individual value therein. Unless indicated otherwise, nomenclature used to describe chemical groups or moieties as used herein follow the convention where, reading the name from left to right, the point of attachment to the rest of the molecule is at the right-hand side of the name. For example, the group "alkylamino" is attached to the rest of the molecule at the amino end, whereas the group "aminoalkyl" is attached to the rest of the molecule at the alkyl end. Unless indicated otherwise, where a chemical group is described by its chemical formula, including a terminal bond moiety indicated by "–" or " ", it will be understood that the attachment is read from the side in which the bond appears. For example, –O-heteroaryl is attached to the rest of the molecule at the oxygen end. "Alkyl" as used herein alone or as part of another group, refers to a fully saturated straight or branched chain hydrocarbon containing from 1 to 20 carbon atoms, which can be referred to as 4   Attorney Docket No.5051.1014.WO a C1-C20 alkyl, and can be substituted or unsubstituted. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, n-decyl, and the like. "Loweralkyl" as used herein, is a subset of alkyl, and, in some embodiments, refers to a saturated straight or branched chain hydrocarbon group containing from 1 to 4 carbon atoms and that can be substituted or unsubstituted. Representative examples of loweralkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, and the like. The term "alkyl" or "loweralkyl" is intended to include both substituted and unsubstituted alkyl or loweralkyl unless otherwise indicated and these groups may be substituted with groups selected from halo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclo, heterocycloalkyl, heteroaryl, hydroxyl, alkoxy, polyalkoxy such as polyethylene glycol, alkenyloxy, alkynyloxy, haloalkoxy, cycloalkoxy, cycloalkylalkyloxy, aryloxy, arylalkyloxy, heterocyclooxy, heterocycloalkyloxy, mercapto, alkyl- S(O)a, haloalkyl-S(O)a, alkenyl-S(O)a, alkynyl-S(O)a, cycloalkyl-S(O)a, cycloalkylalkyl-S(O)a, aryl-S(O)a, arylalkyl-S(O)a, heterocyclo-S(O)a, heterocycloalkyl-S(O)a, amido, amino, carboxy, alkylamino, alkenylamino, alkynylamino, haloalkylamino, cycloalkylamino, cycloalkylalkylamino, arylamino, arylalkylamino, heterocycloamino, heterocycloalkylamino, disubstituted-amino, acylamino, aminoalkyl, alkylphosphonate, alkylnitrile, acyloxy, ester, amide, sulfonamide, urea, carbamate, carboxylate, alkoxyacylamino, aminoacyloxy, nitro or cyano where a is 0, 1, 2 or 3. "Alkenyl" as used herein alone or as part of another group, refers to a straight or branched chain hydrocarbon containing from 1 to 20 carbon atoms (or in loweralkenyl 1 to 4 carbon atoms) that includes 1 to 8 double bonds in the normal chain, and can be referred to as a C1-C20 alkenyl. Representative examples of alkenyl include, but are not limited to, vinyl, 2-propenyl, 3-butenyl, 2-butenyl, 4-pentenyl, 3-pentenyl, 2-hexenyl, 3-hexenyl, 2,4-heptadiene, and the like. The term "alkenyl" or "loweralkenyl" is intended to include both substituted and unsubstituted alkenyl or loweralkenyl unless otherwise indicated and these groups may be substituted with groups as described in connection with alkyl and loweralkyl above. "Alkynyl" as used herein alone or as part of another group, refers to a straight or branched chain hydrocarbon containing from 1 to 20 carbon atoms (or in loweralkynyl 1 to 4 carbon atoms) which include 1 triple bond in the normal chain, and can be referred to as a C1-C20 alkynyl. 5   Attorney Docket No.5051.1014.WO Representative examples of alkynyl include, but are not limited to, 2-propynyl, 3-butynyl, 2- butynyl, 4-pentynyl, 3-pentynyl, and the like. The term "alkynyl" or "loweralkynyl" is intended to include both substituted and unsubstituted alkynyl or loweralkynyl unless otherwise indicated and these groups may be substituted with the same groups as set forth in connection with alkyl and loweralkyl above. "Hydrocarbon" as used herein refers to a moiety including carbon and hydrogen that may be substituted or unsubstituted and may be linear or branched. Exemplary hydrocarbons include, but are not limited to, alkyl, alkenyl, alkynyl, cycloalkyl, and aryl groups as defined herein. "Halo" as used herein refers to any suitable halogen, including –F, -Cl, -Br, and –I. "Mercapto" as used herein refers to an -SH group. "Azido" as used herein refers to an -N3 group. "Cyano" as used herein refers to a -CN group. "Hydroxyl" as used herein refers to an –OH group. "Nitro" as used herein refers to an –NO2 group. "Alkoxy" as used herein alone or as part of another group, refers to an alkyl or loweralkyl group, as defined herein, appended to the parent molecular moiety through an oxy group, -O-. Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2- propoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy and the like. "Acyl" as used herein alone or as part of another group refers to a -C(O)R20group, wherein R20is an alkyl, alkenyl, alkynyl, cycloalkyl, or aryl. "Acyloxy" as used herein alone or as part of another group refers to a -OC(O)R20group, wherein R20is an alkyl, alkenyl, alkynyl, cycloalkyl, or aryl. "Haloalkyl" as used herein alone or as part of another group, refers to at least one halogen, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of haloalkyl include, but are not limited to, chloromethyl, 2- fluoroethyl, trifluoromethyl, pentafluoroethyl, 2-chloro-3-fluoropentyl, and the like. "Alkylthio" as used herein alone or as part of another group, refers to an alkyl group, as defined herein, appended to the parent molecular moiety through a thio moiety, as defined herein. Representative examples of alkylthio include, but are not limited to, methylthio, ethylthio, tert- butylthio, hexylthio, and the like. 6   Attorney Docket No.5051.1014.WO "Cycloalkyl" as used herein alone or as part of another group, refers to a saturated or partially unsaturated cyclic hydrocarbon group containing from 1 to 20 carbon atoms (optionally with a carbon atom replaced in a heterocyclic group as discussed below). A cycloalkyl group may include 0, 1, 2, or more double or triple bonds. A cycloalkyl may be aromatic. Representative examples of cycloalkyl include, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and cyclododecyl. These rings may optionally be substituted with additional substituents as described herein such as halo or loweralkyl. The term "cycloalkyl" is generic and intended to include heterocyclic groups as discussed below unless specified otherwise. "Heterocyclic group" or "heterocyclo" as used herein alone or as part of another group, refers to an aliphatic (e.g., fully or partially saturated heterocyclo) or aromatic heterocyclo (e.g., heteroaryl) ring systems containing at least one heteroatom in a ring. A heterocyclic group may include 1, 2, 3, 4, 5, 6, or more ring systems and examples include monocyclic heterocycles, bicyclic heterocycles, tricyclic heterocycles, and a tetracyclic heterocycles. Monocyclic ring systems are exemplified by any 5 or 6 membered ring containing 1, 2, 3, or 4 heteroatoms independently selected from oxygen, nitrogen and sulfur. The 5 membered ring has from 0-2 double bonds and the 6 membered ring has from 0-3 double bonds. Representative examples of monocyclic ring systems include, but are not limited to, azetidine, azepine, aziridine, diazepine, 1,3-dioxolane, dioxane, dithiane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazoline, isothiazolidine, isoxazole, isoxazoline, isoxazolidine, morpholine, oxadiazole, oxadiazoline, oxadiazolidine, oxazole, oxazoline, oxazolidine, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridine, pyrimidine, pyridazine, pyrrole, pyrroline, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, tetrazine, tetrazole, thiadiazole, thiadiazoline, thiadiazolidine, thiazole, thiazoline, thiazolidine, thiophene, thiomorpholine, thiomorpholine sulfone, thiopyran, triazine, triazole, trithiane, and the like. Bicyclic ring systems are exemplified by any of the above monocyclic ring systems fused to an aryl group as defined herein, a cycloalkyl group as defined herein, or another monocyclic ring system as defined herein. Representative examples of bicyclic ring systems include but are not limited to, for example, benzimidazole, benzothiazole, benzothiadiazole, benzothiophene, benzoxadiazole, benzoxazole, benzofuran, benzopyran, benzothiopyran, benzodioxine, 1,3-benzodioxole, cinnoline, indazole, indole, indoline, indolizine, naphthyridine, isobenzofuran, isobenzothiophene, isoindole, isoindoline, isoquinoline, phthalazine, purine, pyranopyridine, quinoline, quinolizine, quinoxaline, 7   Attorney Docket No.5051.1014.WO quinazoline, tetrahydroisoquinoline, tetrahydroquinoline, thiopyranopyridine, and the like. These rings include quaternized derivatives thereof and may be optionally substituted with groups selected from halo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclo, heterocycloalkyl, hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, cycloalkoxy, cycloalkylalkyloxy, aryloxy, arylalkyloxy, heterocyclooxy, heterocyclolalkyloxy, mercapto, alkyl-S(O)m, haloalkyl-S(O)m, alkenyl-S(O)m, alkynyl-S(O)m, cycloalkyl-S(O)m, cycloalkylalkyl-S(O)m, aryl-S(O)m, arylalkyl-S(O)m, heterocyclo-S(O)m, heterocycloalkyl-S(O)m, amino, alkylamino, alkenylamino, alkynylamino, haloalkylamino, cycloalkylamino, cycloalkylalkylamino, arylamino, arylalkylamino, heterocycloamino, heterocycloalkylamino, disubstituted-amino, acylamino, acyloxy, ester, amide, sulfonamide, urea, alkoxyacylamino, aminoacyloxy, nitro or cyano where m = 0, 1, 2 or 3. Examples of tetracyclic heterocycles include, but are not limited to, tetrapyrroles. "Aryl" as used herein alone or as part of another group, refers to a monocyclic, carbocyclic ring system or a bicyclic, carbocyclic fused ring system having one or more aromatic rings. Representative examples of aryl include, but are not limited to, azulenyl, indanyl, indenyl, naphthyl, phenyl, tetrahydronaphthyl, and the like. The term "aryl" is intended to include both substituted and unsubstituted aryl unless otherwise indicated and these groups may be substituted with the same groups as set forth in connection with alkyl and loweralkyl above. "Arylalkyl" as used herein alone or as part of another group, refers to an aryl group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of arylalkyl include, but are not limited to, benzyl, 2-phenylethyl, 3- phenylpropyl, 2-naphth-2-ylethyl, and the like. "Amino" as used herein means the radical –NH2. "Alkylamino" as used herein alone or as part of another group means the radical –NHR50, wherein R50is an alkyl group. "Ester" as used herein alone or as part of another group refers to a -C(O)OR51radical, wherein R51is an alkyl, cycloalkyl, alkenyl, alkynyl, or aryl. "Formyl" as used herein refers to a -C(O)H group. "Carboxylic acid" as used herein refers to a –C(O)OH group. "Carboxylic ester" as used herein refers to a –C(O)OR52group, wherein R52is an alkyl, cycloalkyl, alkenyl, alkynyl or aryl. 8   Attorney Docket No.5051.1014.WO "Boronate ester" as used herein refers to a –B(O)OR53group, wherein R53is an alkyl, cycloalkyl, alkenyl, alkynyl or aryl. "Phosphate ester" or "phosphoester" as used herein refers to a –P(O)(OR53)2group, wherein each R53is independently an alkyl, cycloalkyl, alkenyl, alkynyl or aryl. "Sulfoester" as used herein refers to a –S(O)2(OR53) group, wherein R53is an alkyl, cycloalkyl, alkenyl, alkynyl or aryl. "Heteroatom" as used herein refers to O, S or N. "Pharmaceutically acceptable" as used herein means that the compound, anion, cation, or composition is suitable for administration to a subject to achieve the treatments described herein, without unduly deleterious side effects in light of the severity of the disease and necessity of the treatment. As used herein, the terms "increase," "increases," "increased," "increasing," "improve," "enhance," and similar terms indicate an elevation in the specified parameter of at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 150%, 200%, 300%, 400%, 500% or more such as compared to another measurable property or quantity (e.g., a control value).. As used herein, the terms "reduce," "reduces," "reduced," "reduction," "inhibit," and similar terms refer to a decrease in the specified parameter of at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 100% such as compared to another measurable property or quantity (e.g., a control value). In some embodiments, the reduction can result in no or essentially no (i.e., an insignificant amount, e.g., less than about 10% or even 5%) detectable activity or amount. Provided according to embodiments of the present invention are compounds that comprise a tetrapyrrole macrocycle; and a water solubilizing group that is attached to the tetrapyrrole macrocycle, optionally wherein the tetrapyrrole macrocycle comprises a radionuclide and / or the water solubilizing group comprises a hydroxyl, carboxylic acid, and / or a methoxy group. A compound and / or method of the present invention may be suitable for radionuclide imaging and / or therapy. The compounds of the present invention comprise a tetrapyrrole macrocycle and a water solubilizing group attached (directly or indirectly) to the tetrapyrrole macrocycle; and the water solubilizing group may comprise a hydroxyl, carboxylic acid, and / or a methoxy group. In some embodiments, a hydroxyl, carboxylic acid, or methoxy group is a terminal hydroxyl, terminal 9   Attorney Docket No.5051.1014.WO carboxylic acid, or terminal methoxy group. In some embodiments, a compound of the present invention comprises a water solubilizing group (e.g., 1, 2, 3, 4, 5, or more water solubilizing groups) attached to a tetrapyrrole macrocycle of the compound, wherein the water solubilizing group increases the solubility of the compound in an aqueous composition (e.g., water) relative to a tetrapyrrole macrocycle without the water solubilizing group. A "radionuclide" as used herein refers to a nuclide that is radioactive. In some embodiments, the radionuclide is a radioactive nuclide such as, but not limited to, a copper radionuclide. Exemplary radionuclides include, but are not limited to,123I,125I,131I,211At,64Cu,67Cu,44Sc,47Sc,67Ga,68Ga,89Zr,99mTc,111In,177Lu,51Mn,52gMn,52mMn,86Y,62Zn,18F, and57Co. In some embodiments, a tetrapyrrole macrocycle chelates a radionuclide. In some embodiments, the radionuclide is covalently attached to the tetrapyrrole macrocycle, which may in some embodiments, be an astatine or iodide radionuclide, e.g.,123I,125I,131I,18F, or211At. In some embodiments, the water solubilizing group comprises a functional group that aids in solubilizing the compound in an aqueous composition, e.g., a functional group that may increase water solubility and / or modify (e.g., increase) the clearance rate of the compound in vivo. Exemplary water solubilizing groups include, but are not limited to, a polyethylene glycol (PEG), glycoside, sulfonate, ammonium, carboxylate, betaine, phosphate, phosphonate, and / or peptide, optionally wherein the water solubilizing group comprises a carboxy-terminated PEG group (e.g., a carboxy-terminated PEG group) and / or an amine terminated group. In some embodiments, the water solubilizing group comprises a glycoside such as, but is not limited to, glucoside, galactoside, glucuronide, and / or galacturonide. In some embodiments, the water solubilizing group comprises an amino acid and / or a peptide, optionally wherein the amino acid and / or peptide comprises one or more charged amino acids, including, but not limited to, arginine (R), lysine (K), histidine (H), aspartic acid (D), and / or glutamic acid (E) and / or one or more polar amino acids, including, but not limited to, serine (S), threonine (T), asparagine (N), and / or glutamine (Q). In some embodiments, the water solubilizing group comprises a polyethylene glycol (PEG) group, optionally wherein the PEG group comprises 1 to 24 PEG units, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 PEG units. In some embodiments, the PEG group has a structure of: -(OCH2CH2)n1X(CH2)m1Y, wherein n1 is an integer of 1 to 24, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24; X is - O-, -NH-, -S-, or absent; m1 is 0 or an integer of 1 to 10, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; 10   Attorney Docket No.5051.1014.WO and Y is -H, -CH3, -C(O)ORx -PO3H2, or -SO3H, wherein Rx is H, or a C1-C5 alkyl, for example, t-butyl. In some embodiments, the PEG group has a structure of : -(CH2CH2O)n1X(CH2)m1Y, wherein n1 is an integer of 1 to 24, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24; X is -O-, -NH-, -S-, or absent; m1 is 0 or an integer of 1 to 10, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; and Y is -H, -CH3, -C(O)ORx, -PO3H2, or -SO3H, wherein Rx is H or a C1-C5 alkyl, for example, t-butyl . In some embodiments, the PEG group may be further substituted with one or more polar groups, for example, a folic acid. In some embodiments, the water solubilizing group comprises a swallowtail group. A swallowtail group may be bound directly or indirectly (e.g., through a linker) to a tetrapyrrole macrocycle. In some embodiments, the swallowtail group has a structure of: -CH((CH2)n2(C(O)O)m2(CH2)p2Y)2, wherein: n2 is an integer of 1 to 20; m2 is 0 or 1; p2 is 0 or an integer of 1 to 10; and Y is -H, -OH, -SH, -NH2, -NHCH3, -OCH3, -PO3H2, -SO3H, or -C(O)OH, optionally wherein Y is -OCH3or -C(O)OH. In some embodiments, the swallowtail group has a structure of: -CH((CH2)n3(OCH2CH2)m3X(CH2)p3Y)2, wherein: n3 is an integer of 1 to 20; m3 is 0 or 1 to 24; X is -O-, -S-, -NH-, or absent; p3 is 0 or an integer of 1 to 10; and Y is -H, -CH3, -C(O)OH, -PO3H2, or -SO3H, optionally wherein Y is -C(O)OH. In some embodiments, the swallowtail group has a structure of: -CH((CH2)n4(C(O)NH)(CH2)m4(OCH2CH2)p4X(CH2)q4Y)2, wherein n4 is an integer of 1 to 20; m4 is 1 to 20; p4 is an integer of 0, or 1 to 24; and X is -O-, -S-, -NH-, or absent; q4 is 0 or an integer of 1 to 24; and Y is -H, -CH3, -C(O)OH, PO3H2, or -SO3H, optionally wherein Y is -C(O)OH. A tetrapyrrole macrocycle of a compound of the present invention may include a porphyrin, chlorin, isobacteriochlorin, and bacteriochlorin, or a derivative thereof. Chlorins and bacteriochlorins and isobacteriochlorins may be regarded as derivatives of porphyrins. Exemplary tetrapyrroles include but are not limited to those described in U.S. Patent Nos. 6,272,038; 6,451,942; 6,420,648; 6,559,374; 6,765,092; 6,407,330; 6,642,376; 6,946,552; 6,603,070; 6,849,730; 7,005,237; 6,916,982; 6,944,047; 7,884,280; 7,332,599; 7,148,361; 7,022,862; 6,924,375; 7,501,507; 7,323,561; 7,153,975; 7,317,108; 7,501,508; 7,378,520; 7,534,807; 7,919,770; 7,799,910; 7,582,751; 8,097,609; 8,187,824; 8,207,329; 7,633,007; 7,745,618; 7,994,312; 8,278,340; 9,303,165; and 9,365,722; and International Application Nos. 11   Attorney Docket No.5051.1014.WO PCT / US17 / 47266 and PCT / US17 / 63251. In embodiments, the tetrapyrrole macrocycle of the compound is a porphyrin. In some embodiments, the tetrapyrrole macrocycle has a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id:   ,  ,    Attorney Docket No.5051.1014.WO ,  ----- indicates a single bond or a double bond; R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12are each independently selected from the group consisting of a hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocyclo, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, aryloxy, arylalkyl, arylalkenyl, aWrylalkynyl, heteroaryl, 13   Attorney Docket No.5051.1014.WO heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, alkoxy, halo, mercapto, azido, cyano, formyl, carboxylic acid, hydroxyl, nitro, acyl, alkylthio, amino, alkylamino, arylalkylamino, disubstituted amino, acylamino, acyloxy, ester, amide, sulfoxyl, sulfonyl, sulfonate, sulfonic acid, sulfonamide, urea, alkoxylacylamino, aminoacyloxy, hydrophilic groups, linking groups, bioconjugatable groups, surface attachment groups, targeting groups, and / or the water solubilizing group (e.g., a swallowtail group), each of which may optionally be substituted; or R1and R2together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R2and R3together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R3and R5together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R4and R5together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R4and R7together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R7and R8together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R9and R10together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or or R10and R11together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; and M1, if present, is a metal (e.g., zinc, magnesium, gold, aluminum, silicon, palladium, indium, tin, copper, or platinum) or a radionuclide, and W is N, O, S, Se, or CH; and wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12comprises the water solubilizing group or is substituted with the water solubilizing group. In some embodiments, the tetrapyrrole macrocycle has a structure of Formula Ia and is a porphyrin have a structure of: 14   Attorney Docket No.5051.1014.WO . In some embodiments, a structure of Formula Ia and is a chlorin having a structure of: .   In some embodiments, a structure of Formula Ia and is a bacteriochlorin having a structure of:   .  In some embodiments, a structure of Formula Ib and is an isobacteriochlorin. In some embodiments, the tetrapyrrole macrocycle has a structure of Formula Ia or Formula Ib and M1is a trivalent metal and / or a lanthanide. In some embodiments, the tetrapyrrole macrocycle has a structure of Formula Ic or Formula Id and is thus in the free base form (e.g., devoid of a metal ion in the cavity / core of the tetrapyrrole macrocycle). In some 15   Attorney Docket No.5051.1014.WO embodiments, the tetrapyrrole macrocycle has a structure of Formula Ic and is a free base porphyrin having a structure of: . In some embodiments, Ic and is a free base chlorin having a structure of: . In some embodiments, Ic and is a free base bacteriochlorin having a structure of: 16   Attorney Docket No.5051.1014.WO .  In some embodiments, Formula Id and is a free base isobacteriochlorin. In some embodiments, the compound has a molecular weight of about 400 Daltons to about 500, 1000, 2500, or 5000 Daltons, e.g., 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900 or 5000 Daltons. The molecular weight of the compound may be about 400 to about 5000 Daltons, 4600 to about 4000 Dalton, 400 to about 3000 Daltons, 400 to about 2000 Daltons, or 400 to about 1000 Daltons. In some embodiments, the compound has a water solubility of at least 0.1 mg / mL, or at least 0.1 M. In some embodiments, the compound has a water solubility of at least 0.1 mg / mL, 0.15 mg / mL, 0.2 mg / mL, 0.25 mg / mL, 0.3 mg / mL, 0.35 mg / mL, 0.4 mg / mL, 0.45 mg / mL, 0.5 mg / mL, 0.55 mg / mL, 0.6 mg / mL, 0.65 mg / mL, 0.7 mg / mL, 0.75 mg / mL, 0.8 mg / mL, 0.85 mg / mL, 0.9 mg / mL, 0.95 mg / mL, 1.0 mg / mL, 2.0 mg / mL, 3.0 mg / mL, 4.0 mg / mL, 5.0 mg / mL, 6.0 mg / mL, 7.0 mg / mL, 8.0 mg / mL, 9.0 mg / mL, 10.0 mg / mL, 11.0 mg / mL, 12.0 mg / mL, 13.0 mg / mL, 14.0 mg / mL, or 15.0 mg / mL. In some embodiments, the compound has a water solubility of at least at least 0.1 M, at least 0.2 M, at least 0.3 M, at least 0.4 M, at least 0.5 M, at least 0.6 M, at least 0.7 M, at least 0.8 M, at least 0.9 M, or at least 1.0 M. In some embodiments, the compound has a water solubility of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 mM. 17   Attorney Docket No.5051.1014.WO In some embodiments, the compound has a logarithm of partition coefficient (LogP) of less than 0, optionally wherein the compound has a LogP of about -0.25 to about -5. In some embodiments, the compound has a LogP of about -0.25 to about -4, about -0.25 to about -3, about -0.25 to about -2, about 0 to about -4, about 0 to about -3.5, about 0 to about -3, about 0 to about - 2.5, or about 0 to about -2. In some embodiments, the compound has a 1-octanol to aqueous composition partitioning ratio in a range of about 1:1.5 or 1:2 to about 1:100 or 1:100,000 (1-octanol : aqueous composition), wherein the aqueous composition is deionized water or phosphate buffered saline at pH 7.4, optionally wherein the PBS is about 0.1 M. In some embodiments, the compound has a 1-octanol to aqueous composition partitioning ratio in a range of about 1:1.5 to about 1:100,000, about 1:1.5 to about 1:75,000, 1:1.5 to about 1:50,000, about 1:1.5 to about 1:25,000, about 1:1.5 to about 1:10,000, about 1:1.5 to about 1:7,500, about 1:1.5 to about 1:5,000, about 1:1.5 to about 1:2,500, about 1:1.5 to about 1:1,000, about 1:1.5 to about 1:750, about 1:1.5 to about 1:500, about 1:1.5 to about 1:250, about 1:1.5 to about 1:100, about 1:2 to about 1:100,000, about 1:2 to about 1:75,000, 1:2 to about 1:50,000, about 1:2 to about 1:25,000, about 1:2 to about 1:10,000, about 1:2 to about 1:7,500, about 1:2 to about 1:5,000, about 1:2 to about 1:2,500, about 1:2 to about 1:1,000, about 1:2 to about 1:750, about 1:2 to about 1:500, about 1:2 to about 1:250, or about 1:2 to about 1:100. In some embodiments, the compound comprises two or more (e.g., 3, 4, 5, 6, or more) water solubilizing groups. In some embodiments, a water solubilizing group is attached at the perimeter of the tetrapyrrole macrocycle. In some embodiments, a water solubilizing group is attached at the perimeter of a tetrapyrrole macrocycle having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, a water solubilizing group is attached at the perimeter of a porphyrin, chlorin, bacteriochlorin, or isobacteriochlorin. In some embodiments, a compound of the present invention comprises a tetrapyrrole macrocycle and a swallowtail group that is bound (directly or indirectly) to an atom of the tetrapyrrole macrocycle. In some embodiments, a tetrapyrrole molecule has a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id and a swallowtail group is attached at one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12, optionally at R3, R6, R9, and / or R12. In some embodiments, the swallowtail group has a structure of 18   Attorney Docket No.5051.1014.WO -CH((CH2)n2(C(O)O)m2(CH2)p2Y)2, wherein: n2 is an integer of 1 to 20; m2 is 0 or 1; p2 is 0 or an integer of 1 to 10; and Y is -H, -OH, -SH, -NH2, -NHCH3, -OCH3, -PO3H2, -SO3H, or -C(O)OH, optionally wherein Y is -OCH3or -C(O)OH. In some embodiments, the swallowtail group has a structure of -CH((CH2)n3(OCH2CH2)m3X(CH2)p3Y)2, wherein: n3 is an integer of 1 to 20; m3 is 0 or 1 to 24; X is -O-, -S-, -NH-, or absent; p3 is 0 or an integer of 1 to 10; and Y is -H, -CH3, -C(O)OH, -PO3H2, or -SO3H, optionally wherein Y is -C(O)OH. In some embodiments, the swallowtail group has a structure of -CH((CH2)n4(C(O)NH)(CH2)m4(OCH2CH2)p4X(CH2)q4Y)2, wherein n4 is an integer of 1 to 20; m4 is 1 to 20; p4 is an integer of 0, or 1 to 24; and X is -O-, -S-, -NH-, or absent; q4 is 0 or an integer of 1 to 24; and Y is -H, -CH3, -C(O)OH, PO3H2, or -SO3H, optionally wherein Y is -C(O)OH. In some embodiments, a compound of the present invention comprises a tetrapyrrole macrocycle having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id with a swallowtail group attached (directly or indirectly) at the perimeter of the tetrapyrrole macrocycle (e.g., at one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12). In some embodiments, the tetrapyrrole macrocycle comprises a porphyrin, a chlorin, a bacteriochlorin, or an isobacteriochlorin with a swallowtail group attached (directly or indirectly) at the perimeter of the tetrapyrrole macrocycle (e.g., at one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12). In some embodiments, a swallowtail group is attached at the 5-position and / or 15-position of a tetrapyrrole macrocycle. In some embodiments, the 5-position corresponds to R3or R6of Formula Ia, Formula Ib, Formula Ic, or Formula Id, and the 15-position corresponds to R9or R12, respectively, of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, a swallowtail group is attached at one or more selected from R3, R6, R9and R12of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, a swallowtail group is attached at R3and R9of Formula Ia, Formula Ib, Formula Ic, or Formula Id and / or at R6and R12of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, a compound of the present invention comprises a tetrapyrrole macrocycle having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id with a first swallowtail group attached at R3of Formula Ia, Formula Ib, Formula Ic, or Formula Id and a second swallowtail group attached at R9of Formula Ia, Formula Ib, Formula Ic, or Formula Id, wherein the first and second swallowtail groups are the same or are different. In some 19   Attorney Docket No.5051.1014.WO embodiments, a compound of the present invention comprises a tetrapyrrole macrocycle having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id with a first swallowtail group attached at R6of Formula Ia, Formula Ib, Formula Ic, or Formula Id and a second swallowtail group attached at R12of Formula Ia, Formula Ib, Formula Ic, or Formula Id, wherein the first and second swallowtail groups are the same or are different. In some embodiments, a compound of the present invention comprises a tetrapyrrole macrocycle having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id with a PEG group attached (directly or indirectly) at the perimeter of the tetrapyrrole macrocycle (e.g., at one or more of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12). In some embodiments, the tetrapyrrole macrocycle comprises a porphyrin, a chlorin, a bacteriochlorin, or an isobacteriochlorin with a swallowtail group attached (directly or indirectly) at the perimeter of the tetrapyrrole macrocycle (e.g., at one or more of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12). In some embodiments, a PEG group is attached (directly or indirectly) at the 5-position and / or 15-position of a tetrapyrrole macrocycle. In some embodiments, the 5-position corresponds to R3or R6of Formula Ia, Formula Ib, Formula Ic, or Formula Id, and the 15-position corresponds to R9or R12, respectively, of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, a PEG group is attached at one or more selected from R3, R6, R9and R12of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, a PEG group is attached (directly or indirectly) at R3and R9of Formula Ia, Formula Ib, Formula Ic, or Formula Id and / or at R6and R12of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, a compound of the present invention comprises a tetrapyrrole macrocycle having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id with a PEG group attached (directly or indirectly) at the 5-position corresponding to R3of Formula Ia, Formula Ib, Formula Ic, or Formula Id and at the 15-position corresponding to R9of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, a compound of the present invention comprises a tetrapyrrole macrocycle having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id with a PEG group attached (directly or indirectly) at the 5-position corresponding to R6of Formula Ia, Formula Ib, Formula Ic, or Formula Id and at the 15-position corresponding to R12of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, a compound of the present invention comprises a linker attached at the 5-position 20   Attorney Docket No.5051.1014.WO and / or 15-position of a tetrapyrrole macrocycle, wherein the linker comprises a PEG group attached directly or indirectly to the linker. In some embodiments, a compound of the present invention comprises a first water solubilizing group and a second water solubilizing group, and the first water solubilizing group is attached at the 5-position of a tetrapyrrole macrocycle having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id (e.g., a porphyrin, bacteriochlorin, chlorin, or isobacteriochlorin) and the second water solubilizing group is attached at the 15-position of the tetrapyrrole macrocycle, optionally wherein the first water solubilizing group and the second water solubilizing group are the same or different. In some embodiments, the water solubilizing group comprises a first water solubilizing group, a second water solubilizing group and a third water solubilizing group, and the first water solubilizing group is attached at the 5-position of the tetrapyrrole macrocycle, optionally having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id, the second water solubilizing group is attached at the 10-position of the tetrapyrrole macrocycle, and the third water solubilizing group is attached at the 15-position of the tetrapyrrole macrocycle, optionally wherein the first water solubilizing group, the second water solubilizing group, and / or the third water solubilizing group are the same or different. In some embodiments, a water solubilizing group is attached at a beta-position or a meso-position of the tetrapyrrole macrocycle, optionally having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id (e.g., a porphyrin, bacteriochlorin, chlorin, or isobacteriochlorin). In some embodiments, a water solubilizing group is attached at trans-meso-positions of the tetrapyrrole macrocycle, optionally having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id (e.g., a porphyrin, bacteriochlorin, chlorin, or isobacteriochlorin) such as at R3and R9of Formula Ia, Formula Ib, Formula Ic, or Formula Id and / or at R6and R12of Formula Ia, Formula Ib, Formula Ic, or Formula Id. In some embodiments, the compound further comprises a first linker, wherein the first linker is attached to the tetrapyrrole macrocycle, optionally having a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id (e.g., a porphyrin, bacteriochlorin, chlorin, or isobacteriochlorin), and to the water solubilizing group. The compound may further comprise a targeting agent (e.g., 1, 2, 3, 4 or more targeting agent(s)), optionally wherein the one or more targeting agent(s) is a cancer target agent. In some embodiments, the compound comprises at least two targeting agents. In some embodiments, the compound further comprises a second linker, wherein the second linker is attached to the 21   Attorney Docket No.5051.1014.WO tetrapyrrole macrocycle and to the targeting agent. Exemplary targeting agents include, but are not limited to, antibodies, peptides, and / or receptors. In some embodiments, the targeting agent is an antibody or fragment thereof, optionally wherein the targeting agent is a monoclonal antibody (mAb) or fragment thereof. Exemplary antibody fragments include, but are not limited to, camelid- derived heavy chain antibodies (HCAbs) and the variable domain of the heavy chain antibodies (VHH), also termed nanobodies. The latter are small (about 15 kDa) and may afford better tumor penetration than the larger full antibodies. In some embodiments, a targeting agent (e.g., antibody) may not recognize every tumor cell type, and instead may recognize only a subset (e.g., a subset that is present in every tumor and every metastasis). In some embodiments, the target for a targeting agent (e.g., an antibody) is a glucosidase (e.g., a β-glucosidase) and / or a glucuronidase (e.g., a β-glucuronidase). Further exemplary targeting agents include, but are not limited to, those described in U.S. Patent No.7,807,136 and 7,615,221. Binding of the targeting agent and target may allow for the target to maintain its activity. In some embodiments, an agent to which a cancer cell targeting agent binds (e.g., a receptor) is expressed on cancer cells at a concentration that is greater than non-cancerous cells such as, for example, at a concentration that is about 2, 3, 4, 5, 6, 7, 8, 9, or 10-fold higher or more. In some embodiments, the targeting agent is any agent or compound that directs the compound to a given target cellular destination such as a cancer cell and / or tumor extracellular space. In some embodiments, a targeting agent binds to and / or targets a receptor on a cell surface such that a compound of the present invention or a portion thereof is bound to the cell surface and / or remains in extracellular space. In some embodiments, a targeting agent (e.g., antibody and / or nanobody) may be substituted with one or more substituent(s), linker(s), and / or water solubilizing group(s), optionally to modify the water solubility and / or clearance time of the compound. In some embodiments, a targeting agent (e.g., antibody and / or nanobody) may be substituted with one or more PEG group(s), optionally to modify the water solubility and / or clearance time of the compound. In some embodiments, a linker (e.g., a first linker and / or a second linker) may comprise a hydrocarbon (e.g., an alkyl group), swallowtail group, aryl (e.g., phenyl or phenol), heterocyclic ring (e.g., a 1,3,5-triazine, 1,2,3-triazole, etc.), amino acid residue (e.g., a D-amino acid residue and / or an L-amino acid residue), peptide, ether, ketone, ester, amide, branched polymer (e.g., a poly(amidoamine) dendrimer), and / or linear polymer (e.g., polyethylene glycol (PEG)), each of which may be unsubstituted or substituted. Further exemplary linkers include, but are not limited 22   Attorney Docket No.5051.1014.WO to, those described in Ertl et al., The most common linkers in bioactive molecules and their bioisosteric replacement network, Bioorg. Med. Chem.81 (2023) 117194, which is incorporated herein by reference in its entirety. In some embodiments, a compound of the present invention comprises a first linker and a second linker that are the same. In some embodiments, a compound of the present invention comprises a first linker and a second linker that are different. Linkers may be selected, for example, based on their orientation in space, water solubility, length, biocompatibility, and / or degradation profile / stability. In some embodiments, the linker may be substituted to constrain motion of the compound. In some embodiments, the linker may comprise an aryl (e.g., phenyl) group that is substituted at one or more positions with a water solubilization group (e.g., a PEG group), for example, as the linker may comprise a 2,6 substituted phenyl group or a 3,5 substituted phenyl group. In an example embodiment, the linker may comprise a disubstituted aryl (e.g., phenyl) group, for example, disubstituted with an aromatic heterocyclic compound (e.g., a triazole). In some embodiments, the linker comprises a phenoxymethyl triazole. In some embodiments, the linker comprises a 2,6 substituted phenyl group or a 3,5 substituted phenyl group that is substituted at the 2,6 or 3,5 positions, respectively, with a phenoxymethyl triazole that is optionally substituted at one or more positions of the triazole with a water solubilization group (e.g., a PEG group). According to some embodiments provided are compositions such as, e.g., pharmaceutical compositions. A pharmaceutical composition of the present invention may comprise a therapeutically effective amount of a compound of the present invention (e.g., a first agent, a second agent, and / or a third agent as described herein) in a pharmaceutically acceptable carrier. Pharmaceutical carriers suitable for administration of a compound of the present invention include any such carriers known to those skilled in the art to be suitable for the particular mode of administration. In some embodiments, a pharmaceutical composition of the present invention is a composition as described in U.S. Patent No. 7,807,136 and 7,615,221 with the active ingredient replaced with a compound of the present invention as the active ingredient. In some embodiments, a compound of the present invention (i.e., active ingredient) may be formulated as the sole pharmaceutically active ingredient in the composition or may be combined with other active ingredients. A composition of the present invention may comprise one or more compounds of the present invention. In some embodiments, the compounds may be formulated into suitable 23   Attorney Docket No.5051.1014.WO pharmaceutical preparations such as solutions, suspensions, tablets, dispersible tablets, pills, capsules, powders, sustained release formulations or elixirs, for oral administration or in sterile solutions or suspensions for parenteral administration, as well as transdermal patch preparation and dry powder inhalers. In some embodiments, the compounds described herein are formulated into pharmaceutical compositions using techniques and procedures well known in the art (see, e.g., Ansel, Introduction to Pharmaceutical Dosage Forms, Fourth Edition 1985, 126). In the compositions, effective concentrations of one or more compounds or pharmaceutically acceptable derivatives thereof may be (are) mixed with a suitable pharmaceutical carrier. The compounds may be derivatized as the corresponding salts, esters, enol ethers or esters, acetals, ketals, orthoesters, hemiacetals, hemiketals, acids, bases, solvates, hydrates or prodrugs prior to formulation. The concentrations of the compounds in the compositions may be effective for delivery of an amount, upon administration, that treats cancer and / or one or more of the symptoms in a subject and / or kills one or more cancer cells in a subject. In some embodiments, the compositions are formulated for single dosage administration. To formulate a composition, the weight fraction of a compound of the present invention is dissolved, suspended, dispersed or otherwise mixed in a selected carrier at an effective concentration such that the treated condition is relieved, prevented, or one or more symptoms may be ameliorated. The active compound may be included in the pharmaceutically acceptable carrier in an amount sufficient to exert a therapeutically useful effect in the absence of undesirable side effects on the subject treated. The therapeutically effective concentration may be determined empirically by testing the compounds in in vitro and / or in vivo systems described herein and in U.S. Pat. No. 5,952,366 to Pandey et al. (1999) and then extrapolated therefrom for dosages for humans. The concentration of an active compound in the pharmaceutical composition may depend on absorption, inactivation and excretion rates of the active compound, the physicochemical characteristics of the compound, the dosage schedule, and / or the amount administered as well as other factors known to those of skill in the art. For example, the amount that is delivered may be sufficient to kill one or more cancer cells as described herein. In some embodiments, a therapeutically effective dosage should produce a serum concentration of the active ingredient of from about 0.1 ng / ml to about 50-100 µg / ml. In one embodiment, a therapeutically effective dosage is from about 0.001, 0.01 or 0.1 to about 10, 100 24   Attorney Docket No.5051.1014.WO or 1000 mg of active compound per kilogram of body weight per day. Pharmaceutical dosage unit forms may be prepared to provide from about 0.01 mg, 0.1 mg or 1 mg to about 500 mg, 1000 mg or 2000 mg, and in one embodiment from about 10 mg to about 500 mg of the active ingredient or a combination of essential ingredients per dosage unit form. The active ingredient may be administered at once, or may be divided into a number of smaller doses to be administered at intervals of time. It is understood that the precise dosage and duration of treatment is a function of the disease being treated and may be determined empirically using known testing protocols or by extrapolation from in vivo and / or in vitro test data. It is to be noted that concentrations and dosage values may also vary with the severity of the condition to be alleviated. It is to be further understood that for any particular subject, specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions, and that the concentration ranges set forth herein are exemplary only and are not intended to limit the scope or practice of the claimed compositions. In instances in which the compounds exhibit insufficient solubility, methods for solubilizing compounds may be used. Such methods are known to those of skill in this art, and include, but are not limited to, using cosolvents, such as dimethylsulfoxide (DMSO), using surfactants, such as TWEENTM, or dissolution in aqueous sodium bicarbonate. Derivatives of the compounds, such as prodrugs of the compounds may also be used in formulating effective pharmaceutical compositions. Upon mixing or addition of the compound(s), the resulting mixture may be a solution, suspension, emulsion or the like. The form of the resulting mixture depends upon a number of factors, including the intended mode of administration and the solubility of the compound in the selected carrier or vehicle. The effective concentration may be sufficient for ameliorating the symptoms of the disease, disorder or condition treated and may be empirically determined. The pharmaceutical compositions may be provided for administration to humans and / or animals in unit dosage forms, such as tablets, capsules, pills, powders, granules, sterile parenteral solutions or suspensions, and oral solutions or suspensions, and oil-water emulsions containing suitable quantities of the compounds or pharmaceutically acceptable derivatives thereof. The pharmaceutically therapeutically active compounds and derivatives thereof are, in one embodiment, formulated and administered in unit-dosage forms or multiple-dosage forms. Unit- 25   Attorney Docket No.5051.1014.WO dose forms as used herein refers to physically discrete units suitable for human and animal subjects and packaged individually as is known in the art. Each unit-dose contains a predetermined quantity of the therapeutically active compound sufficient to produce the desired therapeutic effect, in association with the required pharmaceutical carrier, vehicle or diluent. Examples of unit-dose forms include ampoules and syringes and individually packaged tablets or capsules. Unit-dose forms may be administered in fractions or multiples thereof. A multiple-dose form is a plurality of identical unit-dosage forms packaged in a single container to be administered in segregated unit- dose form. Examples of multiple-dose forms include vials, bottles of tablets or capsules or bottles of pints or gallons. Hence, multiple dose form is a multiple of unit-doses which are not segregated in packaging. Liquid pharmaceutically administrable compositions may, for example, be prepared by dissolving, dispersing, or otherwise mixing an active compound as defined above and optional pharmaceutical adjuvants in a carrier, such as, for example, water, saline, aqueous dextrose, glycerol, glycols, ethanol, and the like, to thereby form a solution or suspension. If desired, the pharmaceutical composition to be administered may also contain minor amounts of nontoxic auxiliary substances such as wetting agents, emulsifying agents, solubilizing agents, pH buffering agents and the like, for example, acetate, sodium citrate, cyclodextrin derivatives, sorbitan monolaurate, triethanolamine sodium acetate, triethanolamine oleate, and other such agents. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa., 15th Edition, 1975. Dosage forms or compositions containing active ingredient in the range of about 0.005% to about 100% with the balance made up from non-toxic carrier may be prepared. Methods for preparation of these compositions are known to those skilled in the art. The contemplated compositions may contain about 0.001%-100% active ingredient, in one embodiment about 0.1- 95%, in another embodiment about 75-85%. In some embodiments, a composition of the present invention may be suitable for oral administration. Oral pharmaceutical dosage forms are either solid, gel or liquid. The solid dosage forms are tablets, capsules, granules, and bulk powders. Types of oral tablets include compressed, chewable lozenges and tablets which may be enteric-coated, sugar-coated or film-coated. Capsules may be hard or soft gelatin capsules, while granules and powders may be provided in non- 26   Attorney Docket No.5051.1014.WO effervescent or effervescent form with the combination of other ingredients known to those skilled in the art. In certain embodiments, the formulations are solid dosage forms, in one embodiment, capsules or tablets. The tablets, pills, capsules, troches and the like may contain one or more of the following ingredients, or compounds of a similar nature: a binder; a lubricant; a diluent; a glidant; a disintegrating agent; a coloring agent; a sweetening agent; a flavoring agent; a wetting agent; an emetic coating; and a film coating. Examples of binders include microcrystalline cellulose, gum tragacanth, glucose solution, acacia mucilage, gelatin solution, molasses, polvinylpyrrolidine, povidone, crospovidones, sucrose and starch paste. Lubricants include talc, starch, magnesium or calcium stearate, lycopodium and stearic acid. Diluents include, for example, lactose, sucrose, starch, kaolin, salt, mannitol and dicalcium phosphate. Glidants include, but are not limited to, colloidal silicon dioxide. Disintegrating agents include crosscarmellose sodium, sodium starch glycolate, alginic acid, corn starch, potato starch, bentonite, methylcellulose, agar and carboxymethylcellulose. Coloring agents include, for example, any of the approved certified water soluble FD and C dyes, mixtures thereof; and water insoluble FD and C dyes suspended on alumina hydrate. Sweetening agents include sucrose, lactose, mannitol and artificial sweetening agents such as saccharin, and any number of spray dried flavors. Flavoring agents include natural flavors extracted from plants such as fruits and synthetic blends of compounds which produce a pleasant sensation, such as, but not limited to peppermint and methyl salicylate. Wetting agents include propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate and polyoxyethylene laural ether. Emetic-coatings include fatty acids, fats, waxes, shellac, ammoniated shellac and cellulose acetate phthalates. Film coatings include hydroxyethylcellulose, gellan gum, sodium carboxymethylcellulose, polyethylene glycol 4000 and cellulose acetate phthalate. The compound, or pharmaceutically acceptable derivative thereof, may be provided in a composition that protects it from the acidic environment of the stomach. For example, the composition may be formulated in an enteric coating that maintains its integrity in the stomach and releases the active compound in the intestine. The composition may also be formulated in combination with an antacid or other such ingredient. When the dosage unit form is a capsule, it may contain, in addition to material of the above type, a liquid carrier such as a fatty oil. In addition, dosage unit forms may contain various other materials which modify the physical form of the 27   Attorney Docket No.5051.1014.WO dosage unit, for example, coatings of sugar and other enteric agents. The compounds may be administered as a component of an elixir, suspension, syrup, wafer, sprinkle, chewing gum or the like. A syrup may contain, in addition to the active compounds, sucrose as a sweetening agent and certain preservatives, dyes and colorings and flavors. The active materials may also be mixed with other active materials which do not impair the desired action, or with materials that supplement the desired action, such as antacids, H2 blockers, and diuretics. The active ingredient is a compound or pharmaceutically acceptable derivative thereof as described herein. Higher concentrations, up to about 98% by weight of the active ingredient may be included. In some embodiments, tablets and capsules formulations may be coated as known by those of skill in the art in order to modify or sustain dissolution of the active ingredient. Thus, for example, they may be coated with a conventional enterically digestible coating, such as phenylsalicylate, waxes and cellulose acetate phthalate. Liquid oral dosage forms include aqueous solutions, emulsions, suspensions, solutions and / or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent granules. Aqueous solutions include, for example, elixirs and syrups. Emulsions are either oil-in-water or water-in-oil. Elixirs are clear, sweetened, hydroalcoholic preparations. Pharmaceutically acceptable carriers used in elixirs include solvents. Syrups are concentrated aqueous solutions of a sugar, for example, sucrose, and may contain a preservative. An emulsion is a two-phase system in which one liquid is dispersed in the form of small globules throughout another liquid. Pharmaceutically acceptable carriers used in emulsions are non-aqueous liquids, emulsifying agents and preservatives. Suspensions use pharmaceutically acceptable suspending agents and preservatives. Pharmaceutically acceptable substances used in non-effervescent granules, to be reconstituted into a liquid oral dosage form, include diluents, sweeteners and wetting agents. Pharmaceutically acceptable substances used in effervescent granules, to be reconstituted into a liquid oral dosage form, include organic acids and a source of carbon dioxide. Coloring and flavoring agents are used in all of the above dosage forms. Solvents include glycerin, sorbitol, ethyl alcohol and syrup. Examples of preservatives include glycerin, methyl and propylparaben, benzoic acid, sodium benzoate and alcohol. Examples of non-aqueous liquids utilized in emulsions include mineral oil and cottonseed oil. Examples of emulsifying agents include gelatin, acacia, tragacanth, bentonite, 28   Attorney Docket No.5051.1014.WO and surfactants such as polyoxyethylene sorbitan monooleate. Suspending agents include sodium carboxymethylcellulose, pectin, tragacanth, xanthan gum, Veegum and acacia. Sweetening agents include sucrose, syrups, glycerin and artificial sweetening agents such as saccharin. Wetting agents include propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate and polyoxyethylene lauryl ether. Organic acids include citric and tartaric acid. Sources of carbon dioxide include sodium bicarbonate and sodium carbonate. Coloring agents include any of the approved certified water soluble FD and C dyes, and mixtures thereof. Flavoring agents include natural flavors extracted from plants such fruits, and synthetic blends of compounds which produce a pleasant taste sensation. For a solid dosage form, the solution or suspension, in for example propylene carbonate, vegetable oils or triglycerides, is in one embodiment encapsulated in a gelatin capsule. Such solutions, and the preparation and encapsulation thereof, are disclosed in U.S. Pat. Nos. 4,328,245; 4,409,239; and 4,410,545. For a liquid dosage form, the solution, e.g., for example, in a polyethylene glycol, may be diluted with a sufficient quantity of a pharmaceutically acceptable liquid carrier, e.g., water, to be easily measured for administration. Alternatively, liquid or semi-solid oral formulations may be prepared by dissolving or dispersing the active compound or salt in vegetable oils, glycols, triglycerides, propylene glycol esters (e.g., propylene carbonate) and other such carriers, and encapsulating these solutions or suspensions in hard or soft gelatin capsule shells. Other useful formulations include those set forth in U.S. Pat. Nos. RE28,819 and 4,358,603. Briefly, such formulations include, but are not limited to, those containing a compound provided herein, a dialkylated mono- or poly-alkylene glycol, including, but not limited to, 1,2-dimethoxymethane, diglyme, triglyme, tetraglyme, polyethylene glycol-350-dimethyl ether, polyethylene glycol-550-dimethyl ether, polyethylene glycol-750- dimethyl ether wherein 350, 550 and 750 refer to the approximate average molecular weight of the polyethylene glycol, and one or more antioxidants, such as butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), propyl gallate, vitamin E, hydroquinone, hydroxycoumarins, ethanolamine, lecithin, cephalin, ascorbic acid, malic acid, sorbitol, phosphoric acid, thiodipropionic acid and its esters, and dithiocarbamates. Other formulations include, but are not limited to, aqueous alcoholic solutions including a pharmaceutically acceptable acetal. Alcohols used in these formulations are any pharmaceutically acceptable water-miscible solvents having one or more hydroxyl groups, including, but not limited 29   Attorney Docket No.5051.1014.WO to, propylene glycol and ethanol. Acetals include, but are not limited to, di(loweralkyl) acetals of loweralkyl aldehydes such as acetaldehyde diethyl acetal. Parenteral administration, in one embodiment characterized by injection, either subcutaneously, intramuscularly or intravenously is also contemplated herein. Injectables may be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. The injectables, solutions and emulsions also contain one or more excipients. Suitable excipients are, for example, water, saline, dextrose, glycerol or ethanol. In addition, if desired, the pharmaceutical compositions to be administered may also contain minor amounts of non-toxic auxiliary substances such as wetting or emulsifying agents, pH buffering agents, stabilizers, solubility enhancers, and other such agents, such as for example, sodium acetate, sorbitan monolaurate, triethanolamine oleate and cyclodextrins. Implantation of a slow-release or sustained-release system, such that a constant level of dosage is maintained (see, e.g., U.S. Pat. No. 3,710,795) is also contemplated herein. Briefly, a compound provided herein is dispersed in a solid inner matrix, e.g., polymethylmethacrylate, polybutylmethacrylate, plasticized or unplasticized polyvinylchloride, plasticized nylon, plasticized polyethyleneterephthalate, natural rubber, polyisoprene, polyisobutylene, polybutadiene, polyethylene, ethylene-vinylacetate copolymers, silicone rubbers, polydimethylsiloxanes, silicone carbonate copolymers, hydrophilic polymers such as hydrogels of esters of acrylic and methacrylic acid, collagen, cross-linked polyvinylalcohol and cross-linked partially hydrolyzed polyvinyl acetate, that is surrounded by an outer polymeric membrane, e.g., polyethylene, polypropylene, ethylene / propylene copolymers, ethylene / ethyl acrylate copolymers, ethylene / vinylacetate copolymers, silicone rubbers, polydimethyl siloxanes, neoprene rubber, chlorinated polyethylene, polyvinylchloride, vinylchloride copolymers with vinyl acetate, vinylidene chloride, ethylene and propylene, ionomer polyethylene terephthalate, butyl rubber epichlorohydrin rubbers, ethylene / vinyl alcohol copolymer, ethylene / vinyl acetate / vinyl alcohol terpolymer, and ethylene / vinyloxyethanol copolymer, that is insoluble in body fluids. The compound diffuses through the outer polymeric membrane in a release rate controlling step. The percentage of active compound contained in such parenteral compositions is highly dependent on the specific nature thereof, as well as the activity of the compound and the needs of the subject. 30   Attorney Docket No.5051.1014.WO Parenteral administration of the compositions includes intravenous, subcutaneous and intramuscular administrations. Preparations for parenteral administration include sterile solutions ready for injection, sterile dry soluble products, such as lyophilized powders, ready to be combined with a solvent just prior to use, including hypodermic tablets, sterile suspensions ready for injection, sterile dry insoluble products ready to be combined with a vehicle just prior to use and sterile emulsions. The solutions may be either aqueous or nonaqueous. If administered intravenously, suitable carriers include physiological saline or phosphate buffered saline (PBS), and solutions containing thickening and solubilizing agents, such as glucose, polyethylene glycol, and polypropylene glycol and mixtures thereof. Pharmaceutically acceptable carriers used in parenteral preparations include aqueous vehicles, nonaqueous vehicles, antimicrobial agents, isotonic agents, buffers, antioxidants, local anesthetics, suspending and dispersing agents, emulsifying agents, sequestering or chelating agents and other pharmaceutically acceptable substances. Examples of aqueous vehicles include Sodium Chloride Injection, Ringers Injection, Isotonic Dextrose Injection, Sterile Water Injection, Dextrose and Lactated Ringers Injection. Nonaqueous parenteral vehicles include fixed oils of vegetable origin, cottonseed oil, corn oil, sesame oil and peanut oil. Antimicrobial agents in bacteriostatic or fungistatic concentrations must be added to parenteral preparations packaged in multiple-dose containers which include phenols or cresols, mercurials, benzyl alcohol, chlorobutanol, methyl and propyl p-hydroxybenzoic acid esters, thimerosal, benzalkonium chloride and benzethonium chloride. Isotonic agents include sodium chloride and dextrose. Buffers include phosphate and citrate. Antioxidants include sodium bisulfate. Local anesthetics include procaine hydrochloride. Suspending and dispersing agents include sodium carboxymethylcellulose, xanthan gum, hydroxypropyl methylcellulose and polyvinylpyrrolidone. Emulsifying agents include Polysorbate 80 (TWEEN™ 80). A sequestering or chelating agent of metal ions includes EDTA. Pharmaceutical carriers also include ethyl alcohol, polyethylene glycol and propylene glycol for water miscible vehicles; and sodium hydroxide, hydrochloric acid, citric acid or lactic acid for pH adjustment. The concentration of the pharmaceutically active compound may be adjusted so that an injection provides an effective amount to produce the desired pharmacological effect. The exact dose depends on the age, weight and condition of the subject or animal as is known in the art. 31   Attorney Docket No.5051.1014.WO The unit-dose parenteral preparations are packaged in an ampoule, a vial or a syringe with a needle. All preparations for parenteral administration must be sterile, as is known and practiced in the art. Illustratively, intravenous or intraarterial infusion of a sterile aqueous solution containing an active compound is an effective mode of administration. Another embodiment is a sterile aqueous or oily solution or suspension containing an active material injected as necessary to produce the desired pharmacological effect. Injectables are designed for local and systemic administration. In one embodiment, a therapeutically effective dosage is formulated to contain a concentration of at least about 0.01% or 0.1% w / w up to about 90% w / w or more, in certain embodiments more than 1% w / w of the active compound to the treated tissue(s). The compound may be suspended in micronized or other suitable form or may be derivatized to produce a more soluble active product or to produce a prodrug. The form of the resulting mixture depends upon a number of factors, including the intended mode of administration and the solubility of the compound in the selected carrier or vehicle. The effective concentration is sufficient for ameliorating the symptoms of the condition and may be empirically determined. In some embodiments, liposomal suspensions, including tissue-targeted liposomes, such as tumor-targeted liposomes, may also be suitable as pharmaceutically acceptable carriers. These may be prepared according to methods known to those skilled in the art. For example, liposome formulations may be prepared as described in U.S. Pat. No.4,522,811. Briefly, liposomes such as multilamellar vesicles (MLV's) may be formed by drying down egg phosphatidyl choline and brain phosphatidyl serine (7:3 molar ratio) on the inside of a flask. A solution of a compound provided herein in phosphate buffered saline lacking divalent cations (PBS) is added and the flask shaken until the lipid film is dispersed. The resulting vesicles are washed to remove unencapsulated compound, pelleted by centrifugation, and then resuspended in PBS. The present invention finds use in both veterinary and medical applications. Subjects suitable to be treated with a method of the present invention include, but are not limited to, mammalian subjects. Mammals of the present invention include, but are not limited to, canines, felines, bovines, caprines, equines, ovines, porcines, rodents (e.g. rats and mice), lagomorphs, primates (e.g., simians and humans), non-human primates (e.g., monkeys, baboons, chimpanzees, gorillas), and the like, and mammals in utero. Any mammalian subject in need of being treated 32   Attorney Docket No.5051.1014.WO according to the present invention is suitable. Mammalian (e.g., human) subjects of both genders and at any stage of development (i.e., neonate, infant, juvenile, adolescent, adult) may be treated according to the present invention. In some embodiments of the present invention, the subject is a mammal and in certain embodiments the subject is a human. Human subjects include both males and females of all ages including fetal, neonatal, infant, juvenile, adolescent, adult, and geriatric subjects as well as pregnant subjects. In particular embodiments of the present invention, the subject is a human adolescent and / or adult. In some embodiments, the subject has or is believed to have cancer, optionally wherein the subject has metastatic cancer. A method of the present invention may also be carried out on animal subjects, particularly mammalian subjects such as mice, rats, dogs, cats, livestock and horses for veterinary purposes, and / or for drug screening and drug development purposes. In some embodiments, the subject is "in need of" or "in need thereof" of a method of the present invention, for example, the subject has findings typically associated with cancer and / or a tumor, is suspected to have cancer and / or a tumor, and / or the subject has cancer and / or a tumor. According to some embodiments of the present invention provided is a method of diagnosing a disease or disorder in a subject, the method comprising administering a compound of the present invention to the subject, thereby diagnosing the disease or disorder in the subject. In some embodiments, a method of treating a subject in need thereof is provided, the method comprising administering a compound of the present invention to the subject, thereby treating the subject. According to some embodiments of the present invention provided is a method of treating a subject (e.g., a subject having a solid tumor) and / or reducing the size of a solid tumor in a subject, the method comprising administering a compound of the present invention to the subject, thereby treating the subject and / or reducing the size of the solid tumor in the subject. In some embodiments, a compound of the present invention is used in a method of treating, detecting and / or diagnosing a disease or disorder, e.g., cancer, optionally in a subject. In some embodiments, a compound of the present invention is designed for use in a method where the compound targets a tumor tissue. In some embodiments, a compound of the invention is administered to a subject, wherein the compound is delivered to a tumor and immobilizes the compound optionally comprising a radionuclide in and / or around the tumor. In some embodiments, a subject may be treated with a radiolabeled compound. Administration of the compound may be chronically or intermittently 33   Attorney Docket No.5051.1014.WO over about 1, 2, 3, 4, 5, 6, 7, or more days to about 1, 2, 3, 4, or more weeks. In some embodiments, a compound may be administered in a manner to allow the compound and / or therapeutic agent and / or radionuclide to accumulate in and / or around a tumor mass. In some embodiments, the compound is administered intravenously. In some embodiments, a method of the present invention may comprise detecting a compound of the present invention and / or radionuclide in the subject. The method can comprise, for example, administering a compound of the present invention that associates and / or immobilized in a cell, or tissue, and / or tumor site; and detecting the compound or a portion thereof, thereby detecting the cell, tissue, and / or agent. In some embodiments, a method of detecting a cell, tissue, and / or tumor in a subject is provided, the method comprising: administering to the subject a compound of the present invention, optionally wherein the compound associates with the cell, tissue, and / or tumor or otherwise aggregates or immobilizes at the cell, tissue and / or tumor site; and detecting the compound or a portion thereof within the subject, thereby detecting the cell, tissue, and / or tumor. In some embodiments, the subject has or is suspected to have cancer. In some embodiments, a method of the present invention further comprises imaging the subject, optionally wherein the imaging is Magnetic Resonance Imaging (MRI), positron emission tomography (PET), and / or Computed Tomography (CT) (e.g., single-photon emission computed tomography (SPECT)). The present invention is explained in greater detail in the following non-limiting examples. EXAMPLES Example 1 Molecular designs that achieve solubility of porphyrins in aqueous media are attractive for diverse applications. The presence of 4-sulfophenyl or 4-N-methylpyridinium groups at the four meso-positions is effective, but the use of fewer substituents is desirable for custom tailoring. Here, five target porphyrins (along with selected copper or zinc chelates) were prepared with PEG groups to understand how distinct designs affect aqueous solubility (where “PEG” refers to an oligoethylene glycol unit). One objective was to employ only one or two pegylated meso-aryl groups so that other meso-positions would be open for synthetic elaboration while retaining a compact structure. The features examined include (i) 2,6- versus 3,5-dipegylated aryl groups; (ii) 34   Attorney Docket No.5051.1014.WO one versus two 2,6-dipegylated aryl groups; (iii) a nonpolar versus ionizable terminus of the PEG moiety (e.g., methyl versus carboxylic acid); and (iv) length of the PEG moiety (e.g., a short versus an intermediate length PEG moiety). In each case, the PEG groups were attached on a porphyrin scaffold bearing one or two bis(2-propynyloxy)aryl groups. Assessment entailed octanol–aqueous solution partitioning (logP values) and aggregation over the concentration range of 0.2–200 µM. A trans-A2free base porphyrin bearing two 2,6-dialkoxyphenyl groups equipped with methyl- terminated PEG6groups gave ~3:1 partitioning in water versus octanol but high overall solubility (at least 12 mM) in water alone; the analogous porphyrin with carboxylic acid-terminated PEG6 groups gave >100:1 partitioning. A trans-AB porphyrin bearing a single 2,6-dialkoxyphenyl group equipped with carboxylic acid-terminated PEG6groups gave 43:1 partitioning in phosphate buffered saline (PBS, pH 7.4) versus octanol but was prone to self-aggregation at 20–200 µM in PBS alone. Results Synthesis (i) Pattern of 2,6- versus 3,5-dipegylated aryl groups. Tetraethynylporphyrin Zn124and mPEG6-azide (I, where the prefix “m” implies methyl termination) were reacted under conditions25,26for copper-mediated click chemistry with tetrapyrroles. The conditions entail the use of CuI, sodium ascorbate, and diisopropylethylamine (DIPEA) in tetrahydrofuran (THF) at reflux. The reaction afforded the corresponding tetra-pegylated porphyrin Zn2 (Scheme 1). The aryl groups are identical and are located at the 5- and 15-positions of the macrocycle, which is denoted as a trans-A2architecture. The zinc chelate was employed to block adventitious metalation of the free base porphyrin by copper, which if occurred would likely thwart the click reaction. 35   Attorney Docket No.5051.1014.WO A facially encumbered porphyrin was prepared by a MacDonald-type condensation27-31(Scheme 2). Thus, condensation of 2,6-bis(prop-2-yn-1-yloxy)benzaldehyde (3)32and dipyrromethane (4)33was carried out upon catalysis by BF3 ^O(Et)2 followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and subsequent neutralization of the Lewis acid with triethylamine (TEA). In this manner, the trans-A2porphyrin 5,15-bis(2,6-bis(2- propynyloxy)phenyl)porphyrin (5) was obtained in 21% yield. Porphyrin 5 was metalated with Zn(OAc)2 ^2H2O in refluxing N,N-dimethylformamide (DMF)34to give the zinc chelate Zn5. a (ii) Terminus of the PEG moiety (methyl versus carboxylic acid). Zinc porphyrin Zn5 and mPEG6-azide were subjected to click reaction to give the corresponding tetra-pegylated zinc porphyrin Zn6 in 71% yield (Scheme 3). To explore the effect of the nature of the metalation state on aqueous solubility, and to gauge the ease of copper insertion for studies in radiochemistry with copper radionuclides,32zinc porphyrin Zn6 was demetalated with trifluoroacetic acid (TFA) at room temperature to give the free base porphyrin 6 in 96% yield. 36   Attorney Docket No.5051.1014.WO Free base porphyrin 6 was then treated overnight with Cu(OAc)2 ^H2O at room temperature, affording the copper chelate Cu6 in quantitative yield. Analogues of porphyrins 6, Zn6, and Cu6 were prepared wherein each PEG group is terminated with an ionizable group. The carboxylic acid was chosen given ionization as the carboxylate at physiological pH as well as commercial availability of the required PEG synthons. Thus, the click reaction of porphyrin Zn5 with azido-PEG6-CO2t-Bu (II) gave Zn7 in 81% yield (Scheme 3). Treatment of the latter with TFA caused removal of the tert-butyl protecting groups and the zinc chelate, affording the free base porphyrin bearing four carboxylic acids (8) in 58% yield. Finally, exposure to copper acetate gave the copper porphyrin Cu8 in 62% yield. Zinc porphyrin Zn8 was prepared in small scale for comparative studies by zincation of free base porphyrin 8. Scheme 3. Synthesis of trans-A2pegylated porphyrins. (iii) One 2,6-dipegylated aryl group. A porphyrin scaffold (Zn9) containing two propynyloxy groups and one TIPS-protected ethyne was recently prepared for successive 37   Attorney Docket No.5051.1014.WO elaboration with PEG and bioconjugatable groups.32Click chemistry with azido-PEG6-CO2t-Bu (II), sodium ascorbate, CuBr, and the ligand tris(hydroxypropyltriazolyl)methylamine (THPTA) followed by removal of the TIPS group with tetra-n-butylammonium fluoride (TBAF) afforded Zn1032in 70% yield (Scheme 4, left panel). Treatment of Zn10 with TFA in CH2Cl2 for 2 h gave, in 94% yield, the free base porphyrin 11 for examination of aqueous solubility. Finally, Cu11 and Zn11 were prepared in small scale by metalation of free base porphyrin 11. (iv) Short PEG chains. The porphyrin scaffold Zn9 also was treated with the short azido-PEG2-CO2t-Bu (III) via click chemistry to create porphyrin Zn12 in 73% yield. Removal of the TIPS group with TBAF gave in 93% yield porphyrin Zn13, a homologue of zinc porphyrin Zn10,32containing PEG2versus PEG6groups. Treatment with TFA in CH2Cl2gave the free base porphyrin 14, a homologue of 11, for studies of aqueous solubility (Scheme 4, right panel). 38   Attorney Docket No.5051.1014.WO Scheme 4. Synthesis of trans-AB pegylated porphyrins. Characterization 39   Attorney Docket No.5051.1014.WO The porphyrins were typically characterized by absorption spectroscopy,1H NMR and13C{1H} NMR spectroscopy, and mass spectrometry. The absorption spectra of trans-A2 and trans-AB free base porphyrins closely resemble those of well-known A4free base porphyrins, with a strong B (Soret) band and a progression of bands in the visible region typically in a phyllo35pattern. The zinc and copper chelates exhibit absorption spectra, particularly in the visible region, that are distinct from the parent free base porphyrin and also distinct from each other. For 6, for example, the most intense visible band is found at 503 nm versus that of Cu6 at 531 nm and of Zn6 at 545 nm. The1H NMR spectrum of each free base or zinc porphyrin exhibited the characteristic resonance of the two meso-protons at δ ^10.12 ppm, and for the free base porphyrins, the NH resonances near δ –3.13 ppm. The δ-pyrrole protons resonated as two doublets in the aromatic region (δ ^9.29 and ^8.98 ppm) for trans-A2 porphyrins and four doublets (δ ^9.36, 9.26, 9.03 and 8.94 ppm) for trans-AB porphyrins. The PEG resonances are described below. The copper chelates were not characterized by NMR spectroscopy given the line broadening caused by relaxation from the copper center.36,37The1H NMR spectrum of the zinc trans-A2 porphyrin with 3,5-dipegylated aryl groups (Zn2) is shown in FIG.1 (top panel). The resonances from the PEG –OCH2CH2– units and the terminal methyl group appear in the range δ ~3.7–3.0 ppm. The1H NMR spectrum of the zinc trans-A2 porphyrin with 2,6-dipegylated aryl groups (Zn6) is shown in FIG.1 (bottom panel). Here, the resonances from the PEG –OCH2CH2– units and the terminal methyl group encompass a much larger range, spanning δ 3.7–2.0 ppm, versus that of Zn2. The peaks in the upfield region of Zn6 are attributed to –OCH2CH2– units thrust over the faces of the macrocycle, thereby experiencing the aromatic ring current. The –OCH2– unit linking the meso-aryl and triazole moieties of Zn6 resonates downfield (δ 5.04 ppm) versus that of Zn2 (δ 4.45 ppm) which is attributed also to the ring current but at the outer edge of the macrocycle. Similarly, the triazolyl–H proton of Zn6 resonates downfield (δ 5.99 ppm) versus that of Zn2 (δ 5.12 ppm), again shifted by the porphyrin ring current. The minimum conclusions are that the 2,6- disubstitution pattern (Zn6) affords facial encumbrance by the attached PEG chains that is not present in the 3,5-disubstitution pattern (Zn2). The structure of Zn5 was confirmed by single-crystal X-ray diffraction upon crystallization from THF at –20 °C (FIG.2). The zinc ion is hexacoordinate with a THF 40   Attorney Docket No.5051.1014.WO molecule at each apical site. The meso-aryl dihedral plane is ca.71° (70.98(4)°). The 2- propynyl groups project over the two faces of the macrocycle. Other analogues include the following substituents on the oxy moieties of 2,6-dialkoxyarylporphyrins: methyl,38-45ethyl,46butyl,47-49octyl,50dodecyl,513,3-dimethylbutyl,524-hydroxybutyl,534-oxa-3-oxoheptyl,54tert- butyldimethylsilyl,55and pentafluorophenylmethyl56. Strapped porphyrins with 2,6-dialkoxyaryl units include doubly strapped meso–meso-linked arrays57and basket-handle thiolate Fe(III) porphyrins.58Assessments in aqueous solution A set of tests was carried out with selected porphyrins to gauge suitability of the designs for use in aqueous solution. (i) LogP measurements. The partitioning of an organic compound between octanol and aqueous solution is a standard proxy to gauge aqueous–membrane partitioning in biological systems.59The partition coefficient (P) for a given porphyrin was examined by allowing a minute quantity of porphyrin to partition between deionized water (or PBS) and octanol at room temperature (~10-4M total porphyrin concentration).60A sample was removed from each phase and examined by absorption spectroscopy in dimethylsulfoxide (DMSO) to determine the concentration. The results are shown in Table 1. Two porphyrins can be regarded as benchmarks: TPS-por is found entirely in the aqueous layer (logP < –2) whereas the fully tert- butyl protected tetraester zinc porphyrin Zn7 is found entirely in the octanol layer (log P >2). Table 1. Aqueous-organic partitioning of porphyrins. Compound Type Projection PEG n Terminus LogP 41   Attorney Docket No.5051.1014.WO Cu11bAB 2,6- 6 –CO2H NDc14bAB 2,6- 2 –CO2H NDc bPBS as the aqueous phase. cNot determined because of insolubility in aqueous solution. Porphyrin Zn2, which bears neutral PEG groups at the 3,5-positions of the two aryl rings, exhibited an extensively broadened Soret band (see the ESI) in water, which is suggestive of aggregation; hence, a logP value was unobtainable. All of the other porphyrins examined bear PEG groups at the 2,6-positions and gave sharp absorption bands at very dilute concentration (2 µM) in aqueous media. The three porphyrins 6, Zn6, and Cu6 each showed preferential partitioning in water versus octanol by a ratio of ~2.5:1. No significant difference was observed as a function of the metalation state: zinc(II), copper(II), or free base. The same phenomena were observed for the series of 8, Zn8, and Cu8; however, the aqueous partitioning decreased along the series 11 (logP = –1.6), Zn11 (–1.1), and Cu11 (insoluble in aqueous media). The lack of solubility of the copper chelate Cu11 versus the zinc chelate Zn11 and free base 11 was surprising and may indicate beneficial solubilization interactions in the latter two cases that are not available in the copper chelate. Such interactions could include aqueous or PEG carboxylate / carboxylic acid oxygenic coordination to the apical zinc site of Zn11, or aqueous or PEG carboxylate / carboxylic acid hydrogen-bonding with the free base N–H moieties of 11. Porphyrin 8, which bears four PEG groups terminated with carboxylic acid moieties (as opposed to methyl groups), was not detected in the organic layer. We denote the ratio as >100:1 and the logP value as < –2. For porphyrins with only two PEG groups, the PEG6groups imparted preference for aqueous solution (11, logP –1.6) whereas the PEG2groups (14) resulted in aggregation in PBS; hence, a log P value could not be determined. (ii) Self-aggregation in aqueous solution. The second test examined self-aggregation as a function of concentration in aqueous solution. The occurrence of self-aggregation can be examined by absorption spectroscopy upon reciprocal change of porphyrin concentration (0.2– 200 µM) and cuvette pathlength (100–0.1 mm).60The results with porphyrin 6, Cu6, 8 and 11 in aqueous solution over the 1000-fold concentration range are shown in FIGs.3-6. Porphyrins 6, Cu6 and 8 showed no change in absorption spectral features consistent with absence of self- 42   Attorney Docket No.5051.1014.WO aggregation over this range. On the other hand, 11 showed slight spectral broadening at 20 µM and extensive broadening at 200 µM, indicative of self-aggregation. The inclusion of 3% bovine serum albumin (BSA), a protein that can solubilize organic molecules in aqueous solution,60resulted in little or no spectral broadening of porphyrin 11 even at 200 µM (see the ESI). During the course of experimentation, stock solutions of porphyrins 6 and 11 were prepared in aqueous solution (see ESI). Porphyrin 6 in water (12 mM) gave an optically clear, bright red solution. Porphyrin 11 (1 mM) in PBS gave a transparent albeit muddy red solution. A muddy appearance is consistent with broadened absorption bands,61and the aforementioned concentration-dependent studies indicated aggregation even at substantially lower concentrations. Discussion Here, three porphyrin scaffolds bearing 2-propynyloxy groups (Zn1, Zn5, Zn9) have been derivatized with PEG groups via click chemistry. It may be little appreciated beyond the aficionado that PEG molecules can afford both organic and aqueous solubility, although a core text states that “PEG will partition in favor of water in a water–benzene system and in favor of methylene chloride in a water–methylene chloride system.”13Assessments pertaining to aqueous solubilization entailed partitioning between octanol and aqueous solution and examination of the absorption spectra as a function of concentration. Methods for calculation of clogP values often give wildly disparate results with porphyrins;62hence, measured values are essential. It warrants emphasis that a logP value is not an indication of solubility per se but rather a partitioning in lipophilic versus aqueous media. Aqueous– organic partitioning and solubility are related yet distinct phenomena. The former represents competition between solubilization in two distinct liquid phases, whereas the latter represents competition between homogeneous dispersion in a liquid phase versus the affinity for the aggregated solid state. Aqueous–organic partitioning is given by a dimensionless value whereas solubility has units such as g / cm3. The overall solubility in water could be low or high but give the same ratio for aqueous–organic partitioning. The main findings are as follows: (i) 2,6-diaryl substitution (Zn6) is superior to 3,5-diaryl substitution (Zn2) for aqueous solubilization. An interpretation is provided in FIG.7. The 2,6-dialkoxyaryl group has constrained motion causing the groups to project above and below the plane, whereas the 3,5- dialkoxyaryl group is not so constrained and can rotate toward planarity with the macrocycle.6343   Attorney Docket No.5051.1014.WO Without wishing to be bound to any particular theory, the latter motion opens the possibility of intermolecular hydrophobic interactions leading to self-aggregation and therefore limited solubility. (ii) PEG groups terminated with carboxylic acid groups provide enhanced aqueous solubility versus simple methyl termination at physiological pH, where the former are predominantly in the carboxylate form. Both trans-A2free base porphyrins 6 (methyl termini) and 8 (carboxylate termini) are aqueous soluble, as evidenced by the logP values (Table 1) and the retention of sharp absorption spectra over a 1000-fold concentration range (FIGS.3-6). The logP values show a key distinction, however the aqueous:octanol ratio is 100:35 for 6 versus >100:1 for 8. (iii) One rather than two water-solubilization motifs suffices to impart a degree of aqueous solubility, which enables use of a trans-AB porphyrin (e.g., 11, two PEG-carboxylates) rather than trans-A2porphyrins (e.g., 8, four PEG-carboxylates). Both 8 and 11 exhibit quite negative logP values (<–2, –1.6; i.e., high aqueous partitioning) but 11 does show signs of self- aggregation at concentrations in the range of 20–200 µM. (iv) The porphyrin bearing two carboxylate-terminated PEG2groups (14) rather than PEG6groups (11) was insufficiently soluble to obtain a logP measurement. Despite the self- aggregation of 11 in the 20–200 µM range, a derivative thereof that contains a folic acid moiety tethered via a PEG5group (clicked onto the 4-ethynylphenyl moiety) did not show signs of self- aggregation across the concentration range of 4.8–480 µM in PBS at room temperature.32Without wishing to be bound to any particular theory, such results indicate that incorporation of a polar motif with 11 substantially increases the aqueous solubility. In summary, the studies reported herein point to molecular designs for achieving aqueous solubilization with porphyrins. The use of only one or two meso-substituents leaves other sites available for substitution. Experimental Section General methods 1H and13C{1H} NMR spectra were recorded (Bruker AscendTM500 and Bruker in CD2Cl2 or CDCl3 at room temperature unless noted 44   Attorney Docket No.5051.1014.WO otherwise. Absorption spectra were collected in toluene or DMSO at room temperature. Matrix- assisted laser desorption ionization mass spectrometry (MALDI-MS) was recorded using a Bruker autoflex® max with the matrix α-cyano-4-hydroxycinnamic acid (α-CHCA). Electrospray ionization mass spectrometry (ESI-MS) data were recorded using a Thermo Fisher Scientific Exactive Plus MS, a benchtop full-scan orbitrap mass spectrometer using heated electrospray ionization. Data are reported for the molecular ion or cationized molecular ion. Single crystal X-ray diffraction (SCXRD) data were collected using the Bruker D8 Venture, running at 100 K with MoK ^ ( ^ = 0.71073 Å). All crystal data and graphics were refined and generated by OLEX2 and Mercury software, respectively. THF was freshly distilled from sodium / benzophenone ketyl and used immediately. Commercially available compounds were used as received. Silica gel (40 ^m average particle size) was used for column chromatography. PBS buffer (1x) was employed at pH 7.4. Compounds Zn1,244,33Zn9,32and Zn1032were prepared as described in the literature. Determination of logP values Values were determined at room temperature following a reported method.60The quantity of porphyrin employed was ~0.2–0.4 mg in a total octanol–aqueous solution of 2 mL giving concentrations of 40–150 µM (i.e., ~10-4M). In each case, octanol refers to 1-octanol. Examination of concentration-dependent self-aggregation Values were determined by reciprocal change of concentration and cuvette pathlength in aqueous media at room temperature following a reported method.60Synthesis procedures and characterization data Zn(II) 5,15-Bis{3,5-bis[1-(1-(3,6,9,12,15,18-hexaoxanonadecyl)-1H-1,2,3-triazol-4- yl)methoxy]phenyl}porphyrin (Zn2). Following a reported method26with some modifications, a solution of zinc porphyrin Zn1 (14 mg, 0.019 mmol) and mPEG6-azide (I, 101 mg, 0.314 mmol) in dry THF (8.0 mL) was treated sequentially with sodium ascorbate (9.3 mg, 0.047 mmol), DIPEA (200 μL, 1.1 mmol), and CuI (5.7 mg, 0.030 mmol). The reaction mixture was allowed to reflux overnight (oil bath). The solution was concentrated under reduced pressure and then diluted in CH2Cl2. The organic phase was washed with water and brine, dried 45   Attorney Docket No.5051.1014.WO (Na2SO4), and concentrated to dryness. The crude product was chromatographed using a gradient [silica, CH2Cl2 / MeOH (25:1) to (19:1) to (15:1)] to afford a red oil (5.4 mg, 15%):1H NMR (500 MHz, CDCl3) δ 10.21 (s, 2H), 9.32 (d, J = 4.4 Hz, 4H), 9.08 (d, J = 4.4 Hz, 4H), 7.81 (s, 4H), 7.45 (s, 4H), 7.04 (s, 2H), 5.13 (s, 4H), 4.45 (s, 8H), 3.73 (s, 8H), 3.37–2.86 (m, 96H);13C{1H} NMR (175 MHz, CDCl3) δ 156.3, 148.6, 148.5, 144.0, 142.4, 131.2, 130.6, 123.2, 118.0, 114.5, 104.9, 100.2, 70.4, 69.3–68.2, 61.0, 57.6, 53.2, 49.3; λabs(toluene) 416, 544, 580 nm; MALDI-MS obsd 2024.02; calcd 2024.90, [M+]; ESI-MS obsd 1035.4384, calcd 1035.4393, [(M + 2Na)2+], M = C96H136N16O28Zn. 5,15-Bis(2,6-bis(2-propynyloxy)phenyl)porphyrin (5). Following a reported method24with some modifications, a solution of aldehyde 3 (2.2 g, 10 mmol) and dipyrromethane 4 (1.5 g, 10 mmol) in CH2Cl2 (500 mL) was treated dropwise with BF3.O(Et)2 (190 μL, 1.54 mmol) over 1 minute. The mixture was stirred at room temperature. Aliquots of the solution were analyzed by absorption spectroscopy to monitor the progress of the reaction. After 1.5 h, the reaction mixture was oxidized by the addition of DDQ (2.3 g, 10 mmol), stirred at room temperature for 15 min, and then neutralized by the addition of triethylamine (2.0 mL, 14 mmol). After 10 min, the resulting mixture was poured onto a silica pad (5 cm ^ 30 cm) and eluted with CH2Cl2. The filtrate was concentrated to dryness under reduced pressure. The crude product was triturated with hexanes / CHCl3to afford a dark-red solid (0.72 g, 21%):1H NMR (700 MHz, CD2Cl2) δ 10.25 (s, 2H), 9.37 (d, J = 4.4 Hz, 4H), 8.99 (d, J = 4.4 Hz, 4H), 7.84 (t, J = 8.8 Hz, 2H), 7.29 (d, J = 8.8 Hz, 4H), 4.43 (s, 8H), 2.37 (t, J = 2.6 Hz, 4H), –3.17 (s, 2H);13C{1H} NMR (175 MHz, CD2Cl2) δ 158.5, 131.5, 130.3, 130.1, 120.3, 110.3, 106.8, 104.5, 78.5, 75.1, 56.3; λabs(toluene) 408, 501, 534, 579 nm; MALDI-MS obsd 678.13, calcd 678.23 [M+]; ESI-MS obsd 679.2335, calcd 679.2339 [(M + H)+], M = C44H30N4O4. Zinc(II) 5,15-Bis(2,6-bis(2-propynyloxy)phenyl)porphyrin (Zn5). A sample of Zn(OAc)2 ^2H2O (1.3 g, 5.8 mmol) was added to a solution of porphyrin 5 (78 mg, 0.12 mmol) in DMF (20.0 mL). The reaction mixture was placed in an oil bath to reflux for 6 h. The mixture was concentrated under reduced pressure. The crude product was dissolved in CH2Cl2, washed with saturated aqueous NaHCO3, water, and brine, and then dried (Na2SO4) and concentrated to give a red solid (55 mg, 64%):1H NMR (500 MHz, CD2Cl2) δ 10.29 (s, 2H), 9.43 (d, J = 4.4 Hz, 4H), 9.06 (d, J = 4.4 Hz, 4H), 7.84 (t, J = 8.6 Hz, 2H), 7.29 (d, J = 8.6 Hz, 4H), 4.41 (d, J = 2.4 Hz, 8H), 2.33 (t, J = 2.4 Hz, 4H);13C{1H} NMR (125 MHz, CD2Cl2) δ 158.5, 150.2, 149.4, 46   Attorney Docket No.5051.1014.WO 131.8, 131.5, 129.9, 121.6, 111.0, 106.8, 105.5, 78.5, 75.0, 56.3; λabs (toluene) 414, 539, 575 nm; MALDI-MS obsd 740.05; calcd 740.15, [M+]; ESI-MS obsd 741.1453, calcd 741.1475 [(M + H)+], M = C44H28N4O4Zn. Porphyrin Zn5 upon slow evaporation from tetrahydrofuran at –20 °C afforded a crystalline sample that was then examined by single-crystal X-ray diffraction. Zn(II) 5,15-Bis{2,6-bis[1-(1-(3,6,9,12,15,18-hexaoxanonadecyl)-1H-1,2,3-triazol-4- yl)methoxy]phenyl}porphyrin (Zn6). Following a reported method26with some modifications, a solution of zinc porphyrin Zn5 (15 mg, 0.020 mmol) and mPEG6-azide (I, 93 mg, 0.29 mmol) in dry THF (8.0 mL) was treated sequentially with sodium ascorbate (10 mg, 0.050 mmol), DIPEA (200 μL, 1.10 mmol), and CuI (5.6 mg, 0.030 mmol) under an argon atmosphere. The reaction mixture was refluxed overnight (oil bath). The solution was concentrated under reduced pressure and then dissolved in CH2Cl2. The organic layer was washed with water and brine, dried (Na2SO4), and concentrated to dryness. The crude product was chromatographed using a gradient [silica, CH2Cl2 / MeOH (25:1) to (15:1) to (9:1)] to afford a red oil (29 mg, 71%):1H NMR (500 MHz, CDCl3) δ 10.12 (s, 2H), 9.29 (d, J = 4.4 Hz, 4H), 8.97 (d, J = 4.4 Hz, 4H), 7.79 (t, J = 8.5 Hz, 2H), 7.25 (d, J = 8.5 Hz, 4H), 5.99 (s, 4H), 5.04 (s, 8H), 3.66 (t, J = 5.2 Hz, 8H), 3.47–3.35 (m, 32H), 3.26 (s, 12H), 3.20 (t, J = 5.0 Hz, 8H), 3.05–3.03 (m, 8H), 2.83 (t, J = 5.0 Hz, 8H), 2.58 (t, J = 5.0 Hz, 8H), 2.28 (t, J = 5.0 Hz, 8H), 2.15 (t, J = 4.0 Hz, 8H), 2.06 (t, J = 4.5 Hz, 8H);13C{1H} NMR (175 MHz, CD2Cl2) δ 159.5, 150.4, 149.2, 143.5, 131.7, 131.6, 130.3, 122.9, 121.9, 111.6, 106.9, 105.1, 72.0_63.2, 58.7, 58.6, 50.9, 49.5; λabs(toluene) 414, 545, 581 nm; MALDI-MS obsd 2025.40; calcd 2024.90, [M+]; ESI-MS obsd 2047.8895, calcd 2047.8894 [(M + Na)+], M = C96H136N16O28Zn. 5,15-Bis{2,6-bis[1-(1-(3,6,9,12,15,18-hexaoxanonadecyl)-1H-1,2,3-triazol-4- yl)methoxy]phenyl}porphyrin (6). A solution of zinc porphyrin Zn6 (18 mg, 8.8 μmol) in CH2Cl2 (6.0 mL) was treated with TFA (40 μmol, 0.52 mmol). The reaction mixture was stirred overnight at room temperature under an argon atmosphere. The solution was neutralized by the addition of saturated aqueous NaHCO3, then washed with water and brine, and dried (Na2SO4). The combined organic extract was concentrated under reduced pressure to give a red oil (17 mg, 96%):1H NMR (700 MHz, CDCl3) δ 10.18 (s, 2H), 9.31 (d, J = 4.4 Hz, 4H), 8.96 (d, J = 4.4 Hz, 4H), 7.80 (t, J = 8.7 Hz, 2H), 7.27 (s, 4H), 6.10 (s, 4H), 5.07 (s, 8H), 3.71 (t, J = 5.2 Hz, 8H), 3.56–3.43 (m, 32H), 3.37–3.35 (m, 8H), 3.31 (s, 12H), 3.27–3.26 (m, 8H), 3.07–3.05 (m, 8H), 2.93 (t, J = 4.4 Hz, 8H), 2.80 (t, J = 4.4 Hz, 8H), 2.47–2.43 (m, 16H), –3.15 (s, 2H);13C{1H} 47   Attorney Docket No.5051.1014.WO NMR (175 MHz, CDCl3) δ 159.2, 143.5, 131.4, 130.8, 122.8, 119.9, 111.3, 106.9, 104.2, 77.2– 69.5, 68.4, 63.2, 59.0, 50.7, 49.5 ; λabs (toluene) 410, 503, 537, 578, 632 nm; MALDI-MS obsd 1963.56; calcd 1963.99, [(M + H)+]; ESI-MS obsd 1985.9752, calcd 1985.9759 [(M + Na)+], M = C96H138N16O28. Cu(II) 5,15-Bis{2,6-bis[1-(1-(3,6,9,12,15,18-hexaoxanonadecyl)-1H-1,2,3-triazol-4- yl)methoxy]phenyl}porphyrin (Cu6). A solution of free base porphyrin 6 (5.2 mg, 2.7 μmol) in CH2Cl2 / MeOH (3.0 mL, 1:2) was treated with Cu(OAc)2^H2O (54 mg, 0.27 mmol). The reaction mixture was stirred overnight at room temperature under an argon atmosphere. The mixture was concentrated under reduced pressure, diluted in CH2Cl2, and neutralized by the addition of saturated aqueous NaHCO3. The organic phase was washed with water and brine, and then dried (Na2SO4). The combined organic extract was concentrated to give a red oil (5.4 mg, 100%) λabs (toluene) 407, 531, 563 nm; MALDI-MS obsd 2046.98; calcd 2046.90, [(M + Na)+]; ESI-MS obsd 2046.8931, calcd 2046.8898 [(M + Na)+], M = C96H136CuN16O28. Zn(II)-5,15-Bis{2,6-Bis[1-(1-(21-tert-butyloxy-21-oxo-3,6,9,12,15,18- hexaoxaheneicosanyl)-1H-1,2,3-triazol-4-yl)methoxy]phenyl}porphyrin (Zn7). Following a reported method26with some modifications, a solution of zinc porphyrin Zn5 (15 mg, 0.020 mmol) and azido-PEG6-CO2t-Bu (II, 70 mg, 0.16 mmol) in dry THF (8.0 mL) was treated with sodium ascorbate (10 mg, 0.050 mmol), DIPEA (200 μL, 1.10 mmol), and CuI (6.0 mg, 0.032 mmol). The reaction mixture was allowed to reflux overnight (oil bath). The mixture was concentrated under reduced pressure and then dissolved in CH2Cl2. The organic phase was washed with water and brine, dried (Na2SO4), and concentrated to dryness under reduced pressure. The crude product was chromatographed using a gradient [silica, CH2Cl2 / MeOH (19:1) to (16:1)] to afford a red oil (40 mg, 81%):1H NMR (700 MHz, CDCl3) δ 10.13 (s, 2H), 9.29 (d, J = 4.3 Hz, 4H), 8.98 (d, J = 4.3 Hz, 4H), 7.78 (t, J = 8.7 Hz, 2H), 7.27–7.17 (m, 4H), 5.99 (s, 4H), 5.05 (s, 8H), 3.69–3.64 (m, 16H), 3.53–3.49 (m, 16H), 3.44 (t, J = 4.9 Hz, 8H), 3.34 (t, J = 4.9 Hz, 8H), 3.18 (t, J = 4.9 Hz, 8H), 2.99 (t, J = 4.9 Hz, 8H), 2.81 (t, J = 4.9 Hz, 8H), 2.47–2.45 (m, 16H), 2.13 (t, J = 4.9 Hz, 8H), 2.04 (t, J = 4.9 Hz, 8H), 1.92 (t, J = 4.9 Hz, 8H), 1.43 (s, 36H);13C{1H} NMR (175 MHz, CDCl3) δ 170.9, 159.3, 150.3, 149.0, 143.5, 131.8, 131.5, 130.3, 122.8, 121.7, 111.5, 106.8, 104.9, 80.5, 70.4–68.8, 68.1, 66.8, 63.3, 49.2, 36.2, 28.1; λabs(toluene) 414, 544, 582 nm; MALDI-MS obsd 2481.87; calcd 2481.17, [M+]; ESI-MS obsd 2504.1593, calcd 2504.1617 [(M + Na)+], M = C120H176N16O36Zn. 48   Attorney Docket No.5051.1014.WO 5,15-Bis{2,6-Bis[1-(1-(21-hydroxy-21-oxo-3,6,9,12,15,18-hexaoxaheneicosanyl)-1H- 1,2,3-triazol-4-yl)methoxy]phenyl}porphyrin (8). A solution of zinc porphyrin Zn7 (19 mg, 7.7 ^mol) in THF (2.0 mL) was treated with TFA (300 ^L). The reaction mixture was stirred at 40 °C (oil bath) for 3 days, then concentrated under reduced pressure. The crude residue was dissolved in CH2Cl2 (25 mL), and water (25 mL) was added followed by triethylamine until pH = 9. The aqueous phase was washed once with CH2Cl2. The aqueous phase was acidified with aqueous 1M HCl until pH = 2, then extracted with CH2Cl2(2 x 25 mL). The combined organic extract was washed with water (25 mL) and brine (25 mL), dried (Na2SO4), and concentrated to give a red oil (9.9 mg, 58%):1H NMR (700 MHz, CDCl3) δ 10.21 (s, 2H), 9.32 (d, J = 4.4 Hz, 4H), 8.96 (d, J = 4.4 Hz, 4H), 7.79 (t, J = 8.6, 2H), 7.27 (m, 4H), 6.14 (s, 4H), 5.09 (s, 8H), 3.73–3.36 (m, 64H), 3.28–2.89 (m, 16H), 2.69–2.68 (m, 8H), 2.54–2.48 (m, 8H), 2.39–2.32 (m, 16H), –3.21 (s, 2H);13C{1H} NMR (175 MHz, CDCl3) δ 175.0, 159.1, 143.5, 131.5, 130.9, 130.8, 123.0, 119.8, 111.3, 106.9, 104.3, 70.3–69.3, 68.3, 66.8, 63.1, 49.6, 35.5; λabs (toluene) 410, 503, 531, 574, 630 nm; ESI-MS obsd 2193.9992, calcd 2194.0013 [(M – H)-], M = C104H146N16O36. Cu(II)-5,15-Bis{2,6-Bis[1-(1-(21-hydroxy-21-oxo-3,6,9,12,15,18- hexaoxaheneicosanyl)-1H-1,2,3-triazol-4-yl)methoxy]phenyl}porphyrin (Cu8). A solution of free base porphyrin 8 (4.1 mg, 1.9 ^mol) in CH2Cl2 / MeOH (3.0 mL, 1:2) was treated with Cu(OAc)2^H2O (54 mg, 0.27 mmol). The mixture was stirred overnight at room temperature, then concentrated under reduced pressure. The crude residue was dissolved in CH2Cl2 and neutralized by the addition of saturated aqueous NaHCO3. The organic layer was washed with water and brine, dried (Na2SO4), and concentrated to give a red oil (2.6 mg, 62%) λabs(toluene) 408, 530, 568 nm; ESI-MS obsd 2254.9144, calcd 2254.9152 [(M – H)-], M = C104H144CuN16O36. 5-{2,6-Bis[1-(1-(21-hydroxy-21-oxo-3,6,9,12,15,18-hexaoxaheneicosanyl)-1H-1,2,3- triazol-4-yl)methoxy]phenyl}-5-(4-ethynylphenyl)porphyrin (11). A solution of zinc porphyrin Zn10 (3.0 mg, 2.0 ^mol) in CH2Cl2 (200 ^L) was treated with TFA (200 ^L). The reaction mixture was stirred at room temperature for 2 h, then concentrated under reduced pressure. The crude residue was dissolved in CH2Cl2(15 mL), and water (15 mL) was added followed by saturated aqueous NaHCO3 / NaOH (20: 1) until pH = 11. The aqueous phase was washed once with CH2Cl2. The aqueous phase was acidified with aqueous 1M HCl until pH = 2, 49   Attorney Docket No.5051.1014.WO then extracted with CH2Cl2 (2 x 15 mL). The combined organic extract was dried (Na2SO4) and concentrated to give a red solid (2.5 mg, 94%):1H NMR (700 MHz, CDCl3) δ 10.28 (s, 2H), 9.41 (d, J = 4.4 Hz, 2H), 9.34 (d, J = 4.4 Hz, 2H), 9.05 (d, J = 4.4 Hz, 2H), 8.99 (d, J = 4.4 Hz, 2H), 8.23 (d, J = 7.8 Hz, 2H), 7.96 (d, J = 7.8 Hz, 2H), 7.80 (t, J = 8.7 Hz, 1H), 7.28 (d, J = 8.7 Hz, 2H), 5.91 (s, 2H), 5.11 (s, 4H), 3.66 (t, J = 5.2 Hz, 4H), 3.61 (t, J = 6.0 Hz, 4H), 3.50–3.37 (m, 12H), 3.36 (s, 1H), 3.32–3.27 (m, 4H), 3.21–3.14 (m, 4H), 3.05–2.99 (m, 4H), 2.87 (t, J = 5.1 Hz, 4H), 2.76 (t, J = 4.7 Hz, 4H), 2.48–2.44 (m, 8H), 2.29–2.24 (m, 4H), 2.15–2.7 (m, 4H), – 3.11 (s, 2H);13C{1H} NMR (175 MHz, CDCl3); δ 174.0, 159.1, 143.7, 142.0, 134.7, 131.9, 131.6, 131.1, 131.0, 130.8, 130.7, 122.8, 121.8, 119.8, 118.1, 111.4, 107.0, 105.0, 83.6, 70.4, 70.2, 70.1, 70.0, 70.0, 69.6, 69.4, 69.3, 69.3, 68.4, 66.5, 63.2, 49.5, 35.1; ESI-MS obsd 1375.5843, calcd 1375.5857 [(M + Na)+], M = C70H84N10O18. Zn(II)-5-(2,6-Bis[1-(1-(9-tert-butyloxy-9-oxo-3,6-dioxanonyl)-1H-1,2,3-triazol-4- yl)methoxy]phenyl)-15-(4-(2-(triisopropylsilyl)ethynyl)phenyl)porphyrin (Zn12). Following a reported method26with some modifications, a solution of zinc porphyrin Zn9 (20 mg, 25 µmol), tert-butyl 1-azido-3,6-dioxanonan-9-oate (III, 52 mg, 0.10 mmol), sodium ascorbate (20 mg, 0.10 mmol), and CuI (9.5 mg, 50 µmol) in dry THF (5.0 mL) was treated with DIPEA (100 μL, 0.57 mmol) under an argon atmosphere. The reaction mixture was stirred at room temperature for 2 h then eluted through a silica pad (2.5 cm x 1 cm) with ethyl acetate. The filtrate was concentrated and chromatographed [silica, CH2Cl2 / ethyl acetate (9:1) to (1:9) then pure ethyl acetate] to afford a red non-crystalline solid (24 mg, 73%):1H NMR (500 MHz, CDCl3) δ 10.05 (s, 2H), 9.28 (d, J = 4.5 Hz, 2H), 9.13 (d, J = 4.4 Hz, 2H), 8.99 (d, J = 4.4 Hz, 2H), 8.78–8.65 (m, 2H), 8.14 (d, J = 7.5 Hz, 2H), 7.89 (d, J = 7.5 Hz, 2H), 7.60 (t, J = 8.5 Hz, 1H), 6.79–6.61 (m, 2H), 4.88 (s, 2H), 3.91 (s, 4H), 2.99 (s, 4H), 2.36–2.11 (m, 8H), 1.75–1.50 (m, 8H), 1.39–1.31 (m, 4H), 1.28 (s, 21H), 1.16 (s, 18H);13C{1H} NMR (125 MHz, CDCl3) δ 170.3, 158.6, 150.3, 149.4, 149.1, 149.0, 143.4, 143.1, 134.5, 131.8, 131.7, 131.4, 130.2, 122.5, 121.6, 121.3, 119.0, 111.1, 107.3, 106.4, 105.3, 91.6, 80.3, 68.5, 68.4, 67.4, 65.6, 62.2, 48.6, 35.0, 27.8, 18.9, 11.5; ESI-MS obsd 1331.5653, calcd 1331.5662 [(M + H)+], M = C71H86N10O10SiZn. Zn(II)-5-(2,6-Bis[1-(1-(9-tert-butyloxy-9-oxo-3,6-dioxanonyl)-1H-1,2,3-triazol-4- yl)methoxy]phenyl)-15-(4-ethynylphenyl)porphyrin (Zn13). A solution of zinc porphyrin Zn12 (24 mg, 18 µmol) in THF (3.6 mL) was treated with TBAF (1.0 M solution in THF, 36 µL, 50   Attorney Docket No.5051.1014.WO 36 µmol) for 5 min. The reaction mixture was concentrated and dissolved in CH2Cl2 (20 mL). The solution was washed with brine (30 mL x 2), saturated aqueous NaHCO3 (30 mL x 2), and then brine (30 mL). The organic phase was then dried (Na2SO4), concentrated, and chromatographed [silica, CH2Cl2 / ethyl acetate (9:1 to 1:2)] to afford a dark red solid (20 mg, 93%):1H NMR (500 MHz, CDCl3) δ 10.04 (s, 2H), 9.28 (d, J = 4.4 Hz, 2H), 9.11 (d, J = 4.4 Hz, 2H), 8.98 (d, J = 4.4 Hz, 2H), 8.70 (d, J = 4.4 Hz, 2H), 8.20–8.14 (m, 2H), 7.94–7.87 (m, 2H), 7.57 (t, J = 8.5 Hz, 1H), 6.65 (d, J = 8.6 Hz, 2H), 4.88 (s, 2H), 3.74 (s, 4H), 3.34 (s, 1H), 2.95 (t, J = 5.4 Hz, 4H), 2.37–2.24 (m, 8H), 1.81–1.67 (m, 8H), 1.45 (t, J = 6.5 Hz, 4H), 1.18 (s, 18H);13C{1H} NMR (125 MHz, CDCl3) δ 170.4, 158.7, 150.4, 149.5, 149.3, 149.1, 144.1, 143.1, 134.7, 131.9, 131.8, 131.6, 130.4, 130.2, 121.5, 121.4, 121.2, 118.8, 111.2, 106.3, 105.5, 84.0, 80.4, 78.2, 68.8, 68.6, 67.5, 65.8, 62.1, 48.7, 35.2, 28.0; ESI-MS obsd 1175.4308, calcd 1175.4328 [(M + H)+], M = C62H66N10O10Zn. 5-(2,6-Bis[1-(1-(9-hydroxy-9-oxo-3,6-dioxanonyl)-1H-1,2,3-triazol-4- yl)methoxy]phenyl)-15-(4-ethynylphenyl)porphyrin (14). A solution of zinc porphyrin Zn13 (11 mg, 10 ^mol) in CH2Cl2(500 ^L) was treated with TFA (500 ^L). The reaction mixture was stirred at room temperature for 2 h, then concentrated under reduced pressure. The crude residue was dissolved in CH2Cl2(15 mL), and water (15 mL) was added followed by saturated aqueous NaHCO3 / NaOH (20:1) until pH = 11. The aqueous phase was washed once with CH2Cl2.The aqueous phase was acidified with aqueous 1M HCl until pH = 2, then extracted with CH2Cl2 (2 x 15 mL). The combined organic extract was dried (Na2SO4) and concentrated to give a red solid (4.4 mg, 44%):1H NMR (500 MHz, CD2Cl2) δ 10.29 (s, 2H), 9.41 (d, J = 4.5 Hz, 2H), 9.36 (d, J = 4.5 Hz, 2H), 9.05 (d, J = 4.4 Hz, 2H), 8.95 (d, J = 4.4 Hz, 2H), 8.24 (d, J = 7.9 Hz, 2H), 7.96 (d, J = 7.9 Hz, 2H), 7.78 (t, J = 8.7 Hz, 1H), 7.25 (d, J = 8.7 Hz, 2H), 6.16 (s, 2H), 5.06 (s, 4H), 3.72 (t, J = 5.0 Hz, 4H), 3.42 (s, 1H), 2.95 (t, J = 5.0 Hz, 4H), 2.82 (t, J = 6.1 Hz, 4H), 2.49–2.42 (m, 4H), 2.39–2.33 (m, 4H), 2.03 (t, J = 6.1 Hz, 4H);13C{1H} NMR (125 MHz, CD2Cl2) δ 175.4, 159.0, 143.5, 142.0, 134.8, 132.0, 131.6, 130.8, 122.9, 121.6, 119.7, 118.2, 111.2, 106.8, 105.0, 83.5, 78.2, 69.3, 69.2, 68.4, 65.6, 63.0, 49.6, 34.4; ESI-MS obsd 1023.3746, calcd 1023.3760 [(M + Na)+], M = C54H52N10O10. For logP measurements, the following porphyrins were prepared in small scale by zincation or cupration of the corresponding free base porphyrin. The products were 51   Attorney Docket No.5051.1014.WO characterized by absorption spectroscopy, fluorescence spectroscopy (for the zinc chelates), and mass spectrometry prior to examination in logP measurements. Zn(II)-5,15-Bis{2,6-Bis[1-(1-(21-hydroxy-21-oxo-3,6,9,12,15,18- hexaoxaheneicosanyl)-1H-1,2,3-triazol-4-yl)methoxy]phenyl}porphyrin (Zn8). Following a reported method,24Zn(OAc)2 ^2H2O (34.5 mg) was added to a solution of free base porphyrin 8 (1.0 mg) in CH2Cl2 / MeOH (570 μL, 9:1). The reaction mixture was stirred at room temperature for 3 h. The mixture was diluted with CH2Cl2(10 mL). The organic phase was washed with water (10 mL) and brine, dried (Na2SO4), and concentrated to dryness: λabs (DMSO) 427, 556, 571 nm; λem600, 652 nm; MALDI-MS obsd 2257.65; calcd 2257.92, [(M + H)+], M = C104H144N16O36Zn. Zn(II)-5-{2,6-Bis[1-(1-(21-hydroxy-21-oxo-3,6,9,12,15,18-hexaoxaheneicosanyl)-1H- 1,2,3-triazol-4-yl)methoxy]phenyl}-5-(4-ethynylphenyl)porphyrin (Zn11). Following a reported method,24Zn(OAc)2^2H2O (60.0 mg) was added to a solution of free base porphyrin 11 (1.0 mg) in CH2Cl2 / MeOH (570 μL, 9:1). The reaction mixture was stirred at room temperature for 3 h. The mixture was diluted with CH2Cl2 (10 mL). The organic phase was washed with water (10 mL) and brine, dried (Na2SO4), and concentrated to dryness: λabs(DMSO) 419, 549, 584 nm; λem591, 643 nm; MALDI-MS obsd 1415.46; calcd 1415.51, [(M + H)+], M = C70H82N10O18Zn. Cu(II)-5-{2,6-Bis[1-(1-(21-hydroxy-21-oxo-3,6,9,12,15,18-hexaoxaheneicosanyl)-1H- 1,2,3-triazol-4-yl)methoxy]phenyl}-5-(4-ethynylphenyl)porphyrin (Cu11). A sample of Cu(OAc)2 ^H2O (45.0 mg) was added to a solution of free base porphyrin 11 (1.0 mg) in CH2Cl2 / MeOH (570 μL, 9:1). The reaction mixture was stirred at room temperature for 30 min. The mixture was diluted with CH2Cl2(10 mL). The organic phase was washed with water (10 mL) and brine, dried (Na2SO4), and concentrated to dryness: λabs (DMSO) 407, 528, 559 nm; MALDI-MS obsd 1436.66; calcd 1436.51, [(M + Na)+], M = C70H82N10O18Cu. 52   Attorney Docket No.5051.1014.WO References 1 P. Hambright, In The Porphyrin Handbook, K. M. Kadish, K. M. Smith and R. Guilard, Eds., Academic Press: San Diego, CA, Vol.3, pp.129–210 (2000). 2 F. Dumoulin, M. Durmuş, V. Ahsen and T. Nyokong, Coord. Chem. Rev., 2010, 254, 2792–2847. 3 S. Pisarek, K. Maximova and D. Gryko, Tetrahedron, 2014, 70, 6685–6715. 4 M. Luciano and C. Brückner, Molecules, 2017, 22, 980. 5 J. Winkelman, Cancer Res., 1962, 22, 589–596. 6 P. Hambright and E. B. Fleischer, Inorg. Chem., 1970, 9, 1757–1761. 7 P. A. Carapellucci and D. Mauzerall, Ann. N. Y. Acad. Sci., 1975, 244, 214–238. 8 N. Matsumoto, M. Taniguchi and J. S. Lindsey, J. Porphyrins Phthalocyanines, 2020, 24, 362–378. 9 P. Thamyongkit, M. Speckbacher, J. R. Diers, H. L. Kee, C. Kirmaier, D. Holten, D. F. Bocian and J. S. Lindsey, J. Org. Chem., 2004, 69, 3700–3710. 10 K. E. Borbas, P. Mroz, M. R. Hamblin and J. S. Lindsey, Bioconjugate Chem., 2006, 17, 638–653. 11 A. Z. Muresan and J. S. Lindsey, Tetrahedron, 2008, 64, 11440–11448. 12 A. K. Mandal, T. Sahin, M. Liu, J. S. Lindsey, D. F. Bocian and D. Holten, New J. Chem., 2016, 40, 9648–9656. 13 J. M. Harris, in Poly(ethylene glycol) Chemistry: Biotechnical and Biomedical Applications; Plenum Press: New York, NY, 1992, pp.1–14. 14 D. Sato, Z. Wu, H. Fujita and J. S. Lindsey, Organics, 2021, 2, 161–273. 15 N. Larson and H. Ghandehari, Chem Mater., 2012, 24, 840–853. 16 A. Kolate, D. Baradia, S. Patil, I. Vhora, G. Kore and A. Misra, J. Control. Release, 2014, 192, 67–81. 17 J. Herzberger, K. Niederer, H. Pohlit, J. Seiwert, M. Worm, F. R. Wurm and H. Frey, Chem. Rev., 2016, 116, 2170–2243. 18 R. Begum and H. Matsuura, J. Chem. Soc., Faraday Trans., 1997, 93, 3839–3848. 19 S. Zalipsky and J. M. 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Soc., 1960, 82, 4384–4389. 53   Attorney Docket No.5051.1014.WO 28 C. Brückner, J. J. Posakony, C. K. Johnson, R. W. Boyle, B. R. James and D. Dolphin, J. Porphyrins Phthalocyanines, 1998, 2, 455–465. 29 B. J. Littler, Y. Ciringh and J. S. Lindsey, J. Org. Chem., 1999, 64, 2864–2872. 30 G. R. Geier III, B. J. Littler and J. S. Lindsey, J. Chem. Soc., Perkin Trans.2, 2001, 701–711. 31 C. K. Chang, Isr. J. Chem., 2016, 56, 130–143. 32 H. A. Houson, Z. Wu, P.-L. D. Cao, J. S. Lindsey and S. E. Lapi, Mol. Pharm., 2024, XX, XX–XX. https: / / doi.org / 10.1021 / acs.molpharmaceut.4c00015 33 J. K. Laha, S. Dhanalekshmi, M. Taniguchi, A. Ambroise and J. S. Lindsey, Org. Process Res. Dev., 2003, 7, 799–812. 34 A. D. Adler, F. R. Longo, F. Kampas and J. Kim, J. Inorg. Nucl. Chem., 1970, 32, 2443–2445. 35 J. E. Falk, Porphyrins and Metalloporphyrins, Elsevier Publishing Co.: Amsterdam, 1964, p.74. 36 G. M. Godziela and H. M. Goff, J. Am. Chem. Soc., 1986, 108, 2237–2243. 37 G. N. La Mar and F. 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Lang, H. Lu, Y. Hu, X. Cui, L. Wojtas and X. P. Zhang, CCDC 1894934: Experimental Crystal Structure Determination, 2019. 45 R. Inoue, M. Yokoyama, I. Maruyama and Y. Morisaki, Chem. Eur. J., 2023, 29, e202301717. 46 S. Choi, S. H. Chae, J. H. Shin, Y. Kim, S.-J. Kim, D. H. Choi and S. J. Lee, Chem. Commun., 2013, 49, 3994–3996. 47 C. Arunkumar, P. Bhyrappa and B. Varghese, Tetrahedron Lett., 2006, 47, 8033– 8037. 48 S. J. Lee, C. D. Malliakas, M. G. Kanatzidis, J. T. Hupp and S. T. Nguyen, Adv. Mater., 2008, 20, 3543–3549. 49 S. H. Chae, K. Y. Lee, S.-J. Kim, S. J. Lee and Y. Kim, Inorg. Chem. Commun., 2016, 69, 40–44. 50 A. Meindl, S. Plunkett, A. A. Ryan, K. J. Flanagan, S. Callaghan and M. O. Senge, Eur. J. Org. Chem, 2017, 3565–3583. 51 S. Choi, C. H. Kim, J.-O. Baeg, H.-J. Son, C. Pac and S. O. Kang, ACS Appl. Energy Mater., 2020, 3, 11581–11596. 54   Attorney Docket No.5051.1014.WO 52 M. P. Nikiforov, U. Zerweck, P. Milde, C. Loppacher, T.-H. Park, H. T. Uyeda, M. J. Therien, L. Eng and D. Bonnell, Nano Lett., 2008, 8, 110–113. 53 A. Zingg, B. Felber, V. Gramlich, L. Fu, J. P. Collman and F. Diederich, Helv. Chim. Acta, 2002, 85, 333–351. 54 P. J. Dandliker, F. Diederich, M. Gross, C. B. Knobler, A. Louati and E. M. Sanford, Angew. Chem. Int. Ed. Engl., 1994, 33, 1739–1742. 55 A. Sen and K. S. Suslick, J. Am. Chem. Soc., 2000, 122, 11565–11566. 56 R. W. Wagner, J. S. Lindsey, I. Turowska-Tyrk and W. R. Scheidt, Tetrahedron, 1994, 50, 11097–11112. 57 T. Ikeda, J. M. Lintuluoto, N. Aratani, Z. S. Yoon, D. Kim and A. Osuka, Eur. J. Org. Chem., 2006, 3193–3204. 58 P. Li, K. Alenezi, S. K. Ibrahim, J. A. Wright, D. L. Hughes and C. J. Pickett, ChemSusChem, 2012, 5, 2361–2375. 59 A. Leo, C. Hansch and D. Elkins, Chem. Rev., 1971, 71, 525–616. 60 Q. Liu, M. Taniguchi, S. Goel and J. S. Lindsey, Dyes Pigments, 2024, 223, 111914. 61 S. F. Mason, in The Chemistry of Synthetic Dyes, K. Venkataraman, K., Ed., Academic Press: NY, 1970, Vol. III, pp 169–221. 62 A. R. M. 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Claims

Attorney Docket No.5051.1014.WO THAT WHICH IS CLAIMED IS:

1. A compound comprising: a tetrapyrrole macrocycle; and a water solubilizing group attached to the tetrapyrrole macrocycle, wherein the water solubilizing group comprises a hydroxyl, carboxylic acid, and / or a methoxy group.

2. The compound of claim 1, wherein the water solubilizing group comprises the carboxylic acid.

3. The compound of claim 1, wherein the water solubilizing group comprises the methoxy group.

4. The compound of any one of claims 1-3, wherein the hydroxyl, carboxylic acid, or methoxy group is a terminal hydroxyl, terminal carboxylic acid, or terminal methoxy group.

5. The compound of any one of claims 1-4, wherein the tetrapyrrole macrocycle is a porphyrin, chlorin, isobacteriochlorin, or bacteriochlorin.

6. The compound of any one of claims 1-5, wherein the water solubilizing group comprises a polyethylene glycol (PEG) group, sulfonate, ammonium, carboxylate, betaine, phosphate, phosphonate, amino acid residue, glycoside and / or peptide, optionally wherein the water solubilizing group comprises a carboxy-terminated PEG group (e.g., carboxy-terminated PEG group) and / or an amine-terminated group.

7. The compound of any one of claims 1-6, wherein the water solubilizing group comprises a glycoside that is a glucoside, galactoside, glucuronide, or galacturonide.

8. The compound of any one of claims 1-7, wherein the water solubilizing group comprises a PEG group, optionally wherein the PEG group comprises 1 to 24 PEG units. 56  Attorney Docket No.5051.1014.WO 9. The compound of claim 8, wherein the PEG group has a structure of: –(OCH2CH2)n1X(CH2)m1Y, wherein: n1 is an integer of 1 to 24; X is -O-, -S-, -NH-, or absent; m1 is 0 or an integer of 1 to 10; and Y is -H, -CH3, -C(O)ORx, -PO3H2, or -SO3H, wherein Rx is H or a C1-C5 alkyl.

10. The compound of any one of claims 1-9, wherein the water solubilizing group comprises a swallowtail group.

11. The compound of claim 10, wherein the swallowtail group has a structure of: -CH((CH2)n2(C(O)O)m2(CH2)p2Y)2, wherein: n2 is an integer of 1 to 20; m2 is 0 or 1; p2 is 0 or an integer of 1 to 10; and Y is -H, -OH, -SH, -NH2, -NHCH3, -OCH3, -PO3H2, -SO3H, or -C(O)OH, optionally wherein Y is -OCH3or -C(O)OH.

12. The compound of claim 10, wherein the swallowtail group has a structure of: -CH((CH2)n3(OCH2CH2)m3X(CH2)p3Y)2, wherein: n3 is an integer of 1 to 20; m3 is 0 or 1 to 24; X is -O-, -S-, -NH-, or absent; p3 is 0 or an integer of 1 to 10; and Y is -H, -CH3, -C(O)OH, -PO3H2, or -SO3H, optionally wherein Y is -C(O)OH.

13. The compound of claim 10, wherein the swallowtail group has a structure of: -CH((CH2)n4(C(O)NH)(CH2)m4(OCH2CH2)p4X(CH2)q4Y)2, 57  Attorney Docket No.5051.1014.WO wherein: n4 is an integer of 1 to 20; m4 is 1 to 20; p4 is 0 or an integer of 1 to 24; X is -O-, -S-, -NH-, or absent; q4 is 0 or an integer of 1 to 10; and Y is -H, -CH3, -C(O)OH, -PO3H2, or -SO3H, optionally wherein Y is -C(O)OH.

14. The compound of any one of claims 1-13, wherein the compound has a molecular weight of about 400 Daltons to about 500, 1000, 2500, or 5000 Daltons.

15. The compound of any one of claims 1-14, wherein the compound has a water solubility of at least 0.1 mg / mL.

16. The compound of any one of claims 1-15, wherein the compound has a logarithm of partition coefficient (LogP) of less than 0, optionally wherein the compound has a LogP of -0.25 to about -5.

17. The compound of any one of claims 1-16, wherein the compound has a 1-octanol to aqueous composition partitioning ratio in a range of about 1:1.5 or 1:2 to about 1:100 or 1:100,000 (1-octanol : aqueous composition), wherein the aqueous composition is deionized water or phosphate buffered saline at pH 7.4, optionally wherein the PBS is about 0.1M.

18. The compound of any one of claims 1-17, wherein the compound comprises two or more (e.g., 3, 4, 5, 6, or more) water solubilizing groups.

19. The compound of any one of claims 1-18, wherein the water solubilizing group is attached at the perimeter of the tetrapyrrole macrocycle. 58  Attorney Docket No.5051.1014.WO 20. The compound of any one of claims 1-19, wherein the water solubilizing group is attached at the 5-position and / or 15-position of the tetrapyrrole macrocycle (e.g., porphyrin, bacteriochlorin, isobacteriochlorin, or chlorin).

21. The compound of claim 20, wherein the water solubilizing group comprises a first water solubilizing group and a second water solubilizing group, and the first water solubilizing group is attached at the 5-position of the tetrapyrrole macrocycle and the second water solubilizing group is attached at the 15-position of the tetrapyrrole macrocycle.

22. The compound of claim 20, wherein the water solubilizing group comprises a first water solubilizing group, a second water solubilizing group and a third water solubilizing group, and the first water solubilizing group is attached at the 5-position of the tetrapyrrole macrocycle, the second water solubilizing group is attached at the 10-position of the tetrapyrrole macrocycle, and the third water solubilizing group is attached at the 15-position of the tetrapyrrole macrocycle.

23. The compound of any one of claims 1-22, wherein the water solubilizing group is attached at a meso-position or at a beta-position of the tetrapyrrole.

24. The compound of any one of claims 1-23, further comprising a first linker, wherein the first linker is attached to the tetrapyrrole macrocycle and the water solubilizing group.

25. The compound of any one of claims 1-24, wherein the tetrapyrrole macrocycle comprises a metal, optionally wherein the metal is copper, zinc, iron, magnesium, gold, aluminum, silicon, palladium, indium, tin, or platinum.

26. The compound of any one of claims 1-25, wherein the tetrapyrrole macrocycle comprises a radionuclide, optionally wherein the radionuclide is64Cu,67Cu,44Sc,47Sc,67Ga,68Ga,89Zr,99mTc,111In,177Lu,51Mn,52gMn,52mMn,86Y,62Zn,123I,125I,131I,211At,18F, or57Co, optionally wherein the radionuclide is a copper radionuclide (e.g.,64Cu or67Cu). 59  Attorney Docket No.5051.1014.WO 27. The compound of any one of claims 1-26, wherein the tetrapyrrole macrocycle has a structure of Formula Ia, Formula Ib, Formula Ic, or Formula Id: ,  , 60  Attorney Docket No.5051.1014.WO , R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12are each independently selected from the group consisting of a hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocyclo, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, aryloxy, arylalkyl, arylalkenyl, arylalkynyl, heteroaryl, heteroarylalkyl, 61  Attorney Docket No.5051.1014.WO heteroarylalkenyl, heteroarylalkynyl, alkoxy, halo, mercapto, azido, cyano, formyl, carboxylic acid, hydroxyl, nitro, acyl, alkylthio, amino, alkylamino, arylalkylamino, disubstituted amino, acylamino, acyloxy, ester, amide, sulfoxyl, sulfonyl, sulfonate, sulfonic acid, sulfonamide, urea, alkoxylacylamino, aminoacyloxy, hydrophilic groups, linking groups, bioconjugatable groups, surface attachment groups, targeting groups, and the water solubilizing group, each of which may optionally be substituted; or R1and R2together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R2and R3together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R3and R5together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R4and R5together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R4and R7together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R7and R8together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or R9and R10together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; or or R10and R11together represent a fused aromatic or heteroaromatic ring system that is substituted or unsubstituted; and M1, if present, is a metal (e.g., zinc, magnesium, gold, aluminum, silicon, palladium, indium, tin, copper, or platinum) or a radionuclide (e.g.,64Cu,67Cu,44Sc,47Sc,67Ga,68Ga,89Zr,99mTc,111In,177Lu,51Mn,52gMn,52mMn,86Y,62Zn,57Co,123I,125I,131I,18F, or211At); and W is N, O, S, Se, or CH, wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12is the water solubilizing group or is substituted with the water solubilizing group. 62  Attorney Docket No.5051.1014.WO 28. The compound of any one of claims 1-27, further comprising a targeting agent (e.g., 1, 2, 3, 4, or more targeting agent(s)), optionally wherein the targeting agent is a cancer target agent and / or optionally wherein the compound comprises at least two targeting agents.

29. The compound of claim 28, further comprising a second linker, wherein the second linker is attached to the tetrapyrrole macrocycle and the targeting agent.

30. A method of diagnosing a disease or disorder in a subject, the method comprising: administering a compound of any one of claims 1-29 to the subject, thereby diagnosing the disease or disorder in the subject.

31. The method of claim 30, wherein the disease or disorder is cancer.

32. A method of treating a subject in need thereof, the method comprising: administering a compound of any one of claims 1-31 to the subject, thereby treating the subject.

33. The method of any one of claims 30-32, wherein the administering comprises intravenously administering the compound to the subject.

34. The method of any one of claims 30-33, further comprising imaging the subject and / or detecting the radionuclide, optionally wherein the imaging and / or detecting is performed using Magnetic Resonance Imaging (MRI), positron emission tomography (PET), and / or Computed Tomography (CT) (e.g., single-photon emission computed tomography (SPECT)).

35. The method of any one of claims 30-34, further comprising detecting the compound and / or radionuclide in the subject.

36. The method of any one of claims 30-35, wherein the subject has or is suspected to have cancer. 63

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