USE OF METAL CHELATORS IN MANAGING INFECTIOUS DISEASES RELATED APPLICATIONS

[0001] The present application claims priority under 35 U.S.C. § 119(e) to U.S.

provisional patent application, U.S.S.N.62/138,862, filed March 26, 2015, which is incorporated herein by reference. GOVERNMENT SUPPORT

[0002] This invention was made with government support under grant number

R37DK049108 awarded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The government has certain rights in the invention. BACKGROUND OF THE INVENTION

[0003] Microbial infection results in a complex biological response of the vascular tissue to pathogens. One of the early responses of host innate immunity is the reactive oxygen species (ROS) production (Spooner et al., Int. J. Mol. Sci.2011, 12, p334-352). ROS production is rapidly elevated during infection, seriving to facilitate pathogen clearance as well as contributing to signaling cascades related to inflammation, cell proliferation, and immune response. Significant ROS may lead to damage of important biomolecules and cells, with potential impact on the whole organism.

[0004] Biofilms are complex communities of microorganisms that are commonly found on a variety of substrates or surfaces that are moist or submerged (Musk et al., Curr. Med. Chem., 2006, 13, 2163). Though primarily populated by bacteria, biofilms can also contain many different individual types of microorganisms, e.g., bacteria, archaea, protozoa, and algae. The formation of biofilms can be thought of as a developmental process in which a few free-swimming (planktonic) bacteria adhere to a solid surface and, in response to appropriate signals, initiate the formation of a complex sessile microcolony existing as a community of bacteria and other organisms. Bacteria within biofilms are usually embedded within a matrix, which can consist of protein, polysaccharide, nucleic acids, or combinations of these macromolecules. The matrix is a critical feature of the biofilm that protects the inhabiting organisms from antiseptics, microbicides, and host cells. It has been estimated that bacteria within biofilms are upwards of 1,000-fold more resistant to conventional antibiotics

(Rasmussen et al., Int. J. Med. Microbiol., 2006, 296, 149). [0005] Biofilms play a significant role in infectious disease. It is estimated that biofilms account for between 50-80% of microbial infections in the body, and that the cost of these infections exceeds $1 billion annually. For example, persistent infections of indwelling medical devices remain a serious problem for patients, because eradication of these infections is virtually impossible. A few diseases in which biofilms have been implicated include endocarditis, otitis media, chronic prostatitis, periodontal disease, chronic urinary tract infections, and cystic fibrosis. The persistence of biofilm populations is linked to their inherent insensitivity to antiseptics, antibiotics, and other antimicrobial compounds or host cells.

[0006] Cystic fibrosis (CF), with 7 million asymptomatic heterozygous carriers, is one of the most common genetic diseases in the United States. Despite significant progress in the management of the symptoms of CF, virtually all CF patients succumb to chronic pulmonary infections. For reasons that are not entirely clear, the airways of CF patients are particularly susceptible to bacterial colonization. CF patients typically become infected with

Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Burkholderia cepacia complex, and nonmucoid Pseudomonas aeruginosa. However, as the patients age, Pseudomona aeruginosa becomes the predominant pulmonary pathogen, present in up to 85% of cultures from patients with advanced disease. Once colonized by Pseudomonas aeruginosa, the organism persists for many years or decades and is never eradicated.

Complications arising from Pseudomonas aeruginosa infections are the leading cause of death among CF patents. Accordingly, there is a need for development of new therapies to treat infectious diseases such as biofilm. SUMMARY OF THE INVENTION

[0007] Microbial infections generally involve generation of reactive oxygen species (ROS). ROS in a living organism can lead to siginificant damage to biomolecules, cells, and tissues. As appreciated in the art, free iron can contribute to the formation of reactive oxygen species. For example, iron ions in biological systems react with oxygen species to produce highly reactive hydroxyl radicals via the Fenton reaction (see scheme below). The hydroxyl radical is a highly effective oxidizing agent, reacting at a diffusion-controlled rate with most organic species, such as nucleic acids, proteins, and lipids. Furthermore, superoxide anions or a biological reductant (e.g., ascorbic acid) can reduce the resulting Fe ⁺³ ion back to Fe ⁺² for continued peroxide reduction, thus a problematic cycle.

[0008] Therefore, microbial infections involve the possibility that reactive oxygen species will come in contact with iron ions to produce highly reactive and damaging hydroxyl radicals. That is, the iron released from red blood cells react with oxygen species produced by inflammatory cells such as neutrophils to produce hydroxyl radicals that cause cell and tissue injury (Lee, Acta Neurochir Suppl., 2011, 112, 101-106). Further, iron is usually a nutrient necessary for the growth of microorganisms. Depriving the organisms of iron by chelating and/or removing iron may contribute to the treatment and/or prevention of infectious diseases.

[0009] In one aspect, the present invention provides a pharmaceutical composition comprising a compound capable of chelating a metal or a pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical composition further comprises an antimicrobial agent (e.g., antibiotics).

[0010] In another aspect, the present invention provides methods to treat and/or prevent an infectious disease comprising administering to a subject in need thereof a therapeutically effective amount of a compound capable of chelating a metal (e.g., compounds of any one of Fomulae (I-A)-(III-A)), or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof, or a pharmaceutical composition as described herein. In certain embodiments, the present invention provides methods of treating and/or preventing an infectious disease comprising administering to a subject in need thereof a therapeutically effective amount of a compound capable of chelating a metal or a pharmaceutical

composition as described herein, and an antimicrobial agent.

[0011] In certain embodiments, the infectious disease is caused by bacteria, algae, fungi, parasites, or protozoa. In certain embodiments, the infectious disease is a bacterial infection. In certain embodiments, the bacterial infection is chronic bacterial infection. In certain embodiments, the bacterial infections include, but are not limited to, urinary tract infections, gastritis, respiratory infections (e.g., those in patient’s with cystic fibrosis), cystitis, pyelonephritis, osteomyelitis, bacteremia, skin infections, rosacea, acne, chronic wound infection, infectious kidney stones, bacterial endocarditis, ear infections, and sinus infections. In certain embodiments, the infectious disease is caused by Gram-negative bacteria such as Pseudomonas. In certain embodiments, the subject having or susceptible to the infectious disease also contracts another disease or condition. In certain embodiments, the subject is diagnosed with cystic fibrosis.

[0012] In certain embodiments, the infectious disease is responsive to the chelation or sequestration of a metal. In certain embodiments, the metal is a monovalent, divalent, tetravalent, pentavalent, or hexavalent metal. In certain embodiments, the metal is a trivalent metal. In certain embodiments, the metal is aluminum, thallium, chromium, magnesium, calcium, strontium, nickel, manganese, cobalt, copper, zinc, silver, sodium, potassium, cadmium, mercury, lead, antimony, molybdenum, tungsten, a lanthanide (e.g., cerium), or an actinide (e.g., uranium).. In certain embodiments, the metal being chelated or sequestered is iron (e.g., Fe(III)).

[0013] In another aspect, the present invention provides methods to kill bacteria comprising contacting the bacteria with a compound capable of chelating a metal, or a pharmaceutically acceptable salt thereof.

[0014] In another aspect, the present invention provides methods for inhibiting bacterial cell growth comprising contacting the bacteria with a compound capable of chelating a metal, or a pharmaceutically acceptable salt thereof.

[0015] In another aspect, the present invention provides methods for inducing bacterial hypersusceptibility comprising contacting a bacterium with a compound capable of chelating a metal, or a pharmaceutically acceptable salt thereof.

[0016] In another aspect, the present invention provides methods of treating or preventing biofilm formation comprising administering to a subject in need thereof a therapeutically effective amount of a compound capable of chelating a metal (e.g., compounds of any one of Fomulae (I-A)-(III-A)), or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof, or a pharmaceutical composition as described herein. In certain embodiments, the present invention provides methods of treating or preventing biofilm formation comprising administering to a subject in need thereof a therapeutically effective amount of a compound capable of chelating a metal or a pharmaceutical

composition as described herein, and an antimicrobial agent. In certain embodiments, the biofilms include one or more microorganisms selected from the group consisting of bacteria, archaea, protozoa, fungi and algae. In some embodiments, the biofilms include bacteria.

[0017] In another aspect, the present invention provides compositions for treating or preventing biofilm formation comprising a compound capable of chelating a metal and a carrier. In certain embodiments, the composition is a cleaning composition. [0018] In another aspect, the present invention provides methods of treating or preventing biofilm formation comprising contacting an object with an effective amount of a compound capable of chelating a metal or the composition as described herein. In certain embodiments, the provided method is to inhibit or remove the biofilm on the surface of the object.

[0019] In certain embodiments, the biofilm is produced by an organism selected from the group consisting of bacteria, algae, fungi and protozoa. In some embodiments, the biofilm is bacterial biofilm.

[0020] In certain embodiments, the compound useful in the present invention is of any one of Formulae (I-A)-(III-A), or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[0021] In certain embodiments, the compound is of Formula (I-A):

or a pharmaceutically acceptable salt thereof.

[0022] In certain embodiments, the compound is of Formula (II-A):

or a pharmaceutically acceptable salt thereof.

[0023] In certain embodiments, the compound is of Formula (III-A):

or a pharmaceutically acceptable salt thereof.

[0024] Without wishing to be bound by any particular theory, the compounds provided herein (e.g., any one of Formulae (I-A)-(III-A)) may chelate iron and/or other metals (e.g., aluminum, thallium, chromium, magnesium, calcium, strontium, nickel, manganese, cobalt, copper, zinc, silver, sodium, potassium, cadmium, mercury, lead, antimony, molybdenum, tungsten, a lanthanide (e.g., cerium), or an actinide (e.g., uranium)). In certain embodiments, the compounds chelate iron and one or more metals important for bacterial growth, e.g., K, Mg, Ca, Mn, Zn, Co, Cu, and Mo.

[0025] In yet another aspect, the invention provides a kit for treating and/or preventing an infectious disease. In yet another aspect, the invention provides a kit for treating and/or preventing formation of biofilms. In certain embodiments, the kit is to treat or prevent biofilm formation in a subject. In certain embodiments, the kit is to treat or prevent biofilm formation on an object (e.g., surface). In certain embodiments, the kit further comprises an

antimicrobial agent (e.g., antibiotics). In certain embodiments, the inventive kits include a first container containing a therapeutically effective amount of a compound capable of chelating a metal (e.g., a compound of any one of Formulae (I-A)-(III-A)), or a

pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof; and instructions for administering the compound to the subject to treat and/or prevent an infectious disease and/or biofilm formation in a subject. In certain embodiments, the inventive kits include a first container containing a therapeutically effective amount of a compound capable of chelating a metal (e.g., a compound of any one of Formulae (I-A)-(III- A)), or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof; and an antimicrobial agent; and a second container containing

instructions for administering the compound to the subject to treat and/or prevent an infectious disease and/or biofilm formation. In certain embodiments, the inventive kits include a first container containing a therapeutically effective amount of a compound capable of chelating a metal (e.g., a compound of any one of Formulae (I-A)-(III-A)), or a salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof; and instructions for contacting the compound with an object to treat and/or prevent biofilm formation. In certain embodiments, the kit is a cleaning kit. In certain embodiments, the kit further comprises a disinfectant. A kit may also include multiple unit dosages, for example, for multiple days of treatment.

[0026] The details of one or more embodiments of the invention are set forth herein. Other features, objects, and advantages of the invention will be apparent from the Detailed Description, Examples, and Claims. DEFINITIONS

[0027] Definitions of specific functional groups and chemical terms are described in more detail below. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75 ^th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March March’s Advanced Organic Chemistry, 5 ^th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; Carruthers, Some Modern Methods of Organic Synthesis, 3 ^rd Edition, Cambridge University Press, Cambridge, 1987.

[0028] It is to be understood that compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed“isomers.” Isomers that differ in the arrangement of their atoms in space are termed“stereoisomers.” Stereoisomers that are not mirror images of one another are termed “diastereomers,” and those that are non-superimposable mirror images of each other are termed“enantiomers”. When a compound has an asymmetric center, for example, a carbon atom of the compound is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates plane polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a“racemic mixture.” For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and

Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw–Hill, NY, 1962); Wilen, Tables of Resolving Agents and Optical Resolutions p.268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). The invention additionally encompasses compounds described herein as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers.

[0029] Where an isomer/enantiomer is preferred, it may, in some embodiments, be provided substantially free of the corresponding enantiomer, and may also be referred to as “optically enriched” or“enantiomerically enriched.”“Optically enriched” and

“enantiomerically enriched” means that a provided compound is made up of a significantly greater proportion of one enantiomer. In certain embodiments, a compound of the present invention is made up of at least about 70% by weight of a preferred enantiomer. In certain embodiments, a compound of the present invention is made up of at least about 80% by weight of a preferred enantiomer. In certain embodiments, a compound of the present invention is made up of at least about 90% by weight of a preferred enantiomer. In other embodiments the compound is made up of at least about 95%, 98%, or 99% by weight of a preferred enantiomer. Preferred enantiomers may be isolated from racemic mixtures by any method known to those skilled in the art, including chiral high pressure liquid

chromatography (HPLC) and the formation and crystallization of chiral salts or prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, Tables of Resolving Agents and Optical Resolutions p.268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972).

[0030] Unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the depicted structures that differ only in the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by ¹³ C or ¹⁴ C are within the scope of this invention. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents in accordance with the present invention.

[0031] In a formula, is a single bond where the stereochemistry of the moieties immediately attached thereto is not specified, is absent or a single bond, and or is a single or double bond.

[0032] When a range of values is listed, it is intended to encompass each value and sub- range within the range. For example“C _1–6 ” is intended to encompass, C ₁ , C ₂ , C ₃ , C ₄ , C ₅ , C ₆ , C _1–6 , C _1–5 , C _1–4 , C _1–3 , C _1–2 , C _2–6 , C _2–5 , C _2–4 , C _2–3 , C _3–6 , C _3–5 , C _3–4 , C _4–6 , C _4–5 , and C _5–6 .

[0033] The terms“purified,”“substantially purified,” and“isolated” refer to a compound useful in the present invention being free of other, dissimilar compounds with which the compound is normally associated in its natural state, so that the compound comprises at least 0.5%, 1%, 5%, 10%, 20%, 50%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% of the mass, by weight, of a given sample or composition. In one embodiment, these terms refer to the compound comprising at least 95%, 98%, 99%, or 99.9% of the mass, by weight, of a given sample or composition.

[0034] The term“acyl” refers to a group having the general formula–C(=O)R ^X1 ,– C(=O)OR ^X1 ,–C(=O)–O–C(=O)R ^X1 ,–C(=O)SR ^X1 ,–C(=O)N(R ^X1 ) ₂ ,–C(=S)R ^X1 ,–

C(=S)N(R ^X1 ) ₂ , and–C(=S)S(R ^X1 ),–C(=NR ^X1 )R ^X1 ,–C(=NR ^X1 )OR ^X1 ,–C(=NR ^X1 )SR ^X1 , and– C(=NR ^X1 )N(R ^X1 ) ₂ , wherein R ^X1 is hydrogen; halogen; substituted or unsubstituted hydroxyl; substituted or unsubstituted thiol; substituted or unsubstituted amino; substituted or unsubstituted acyl, cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched

heteroaliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkenyl; substituted or unsubstituted alkynyl; substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy,

heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, mono- or di- aliphaticamino, mono- or di- heteroaliphaticamino, mono- or di- alkylamino, mono- or di- heteroalkylamino, mono- or di-arylamino, or mono- or di-heteroarylamino; or two R ^X1 groups taken together form a 5- to 6-membered heterocyclic ring. Exemplary acyl groups include aldehydes (–CHO), carboxylic acids (–CO ₂ H), ketones, acyl halides, esters, amides, imines, carbonates, carbamates, and ureas. Acyl substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted).

[0035] The term“acyloxy” refers to a“substituted hydroxyl” of the formula (–OR ⁱ ), wherein R ⁱ is an optionally substituted acyl group, as defined herein, and the oxygen moiety is directly attached to the parent molecule. [0036] The term“aliphatic” includes both saturated and unsaturated, nonaromatic, straight chain (i.e., unbranched), branched, acyclic, and cyclic (i.e., carbocyclic)

hydrocarbons, which are optionally substituted with one or more functional groups. As will be appreciated by one of ordinary skill in the art,“aliphatic” is intended herein to include, but is not limited to, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl moieties. Thus, the term“alkyl” includes straight, branched and cyclic alkyl groups. An analogous convention applies to other generic terms such as“alkenyl”,“alkynyl”, and the like.

Furthermore, the terms“alkyl”,“alkenyl”,“alkynyl”, and the like encompass both substituted and unsubstituted groups. In certain embodiments,“aliphatic” is used to indicate those aliphatic groups (cyclic, acyclic, substituted, unsubstituted, branched or unbranched) having 1–20 carbon atoms. Aliphatic group substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy,

heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted).

[0037] The term“alkyl” refers to saturated, straight- or branched-chain hydrocarbon radicals derived from a hydrocarbon moiety containing between one and twenty carbon atoms by removal of a single hydrogen atom. In some embodiments, the alkyl group employed in the invention contains 1–20 carbon atoms. In another embodiment, the alkyl group employed contains 1–15 carbon atoms. In another embodiment, the alkyl group employed contains 1–10 carbon atoms. In another embodiment, the alkyl group employed contains 1–8 carbon atoms. In another embodiment, the alkyl group employed contains 1–5 carbon atoms. Examples of alkyl radicals include, but are not limited to, methyl (e.g., unsubstituted methyl (Me)), ethyl (e.g., unsubstituted ethyl (Et)), propyl (e.g., unsubstituted propyl (Pr)), n-propyl, isopropyl, butyl (e.g., unsubstituted butyl (Bu)), n-butyl, iso-butyl, sec-butyl, sec-pentyl, iso-pentyl, tert- butyl, n-pentyl, neopentyl, n-hexyl, sec-hexyl, n-heptyl, n-octyl, n-decyl, n-undecyl, dodecyl, and the like, which may bear one or more sustitutents. Alkyl group substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted).

[0038] The term“alkenyl” denotes a monovalent group derived from a straight- or branched-chain hydrocarbon moiety having at least one carbon-carbon double bond by the removal of a single hydrogen atom. In certain embodiments, the alkenyl group employed in the invention contains 2–20 carbon atoms. In some embodiments, the alkenyl group employed in the invention contains 2–15 carbon atoms. In another embodiment, the alkenyl group employed contains 2–10 carbon atoms. In still other embodiments, the alkenyl group contains 2–8 carbon atoms. In yet other embodiments, the alkenyl group contains 2–5 carbons. Alkenyl groups include, for example, ethenyl, propenyl, butenyl, 1-methyl-2-buten- 1-yl, and the like, which may bear one or more substituents. Alkenyl group substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted). In an alkenyl group, a C=C double bond for which the stereochemistry is not specified (e.g.,–CH=CHCH ₃ , , ) may be in the (E)- or (Z)-configuration.

[0039] The term“alkynyl” refers to a monovalent group derived from a straight- or branched-chain hydrocarbon having at least one carbon-carbon triple bond by the removal of a single hydrogen atom. In certain embodiments, the alkynyl group employed in the invention contains 2–20 carbon atoms. In some embodiments, the alkynyl group employed in the invention contains 2–15 carbon atoms. In another embodiment, the alkynyl group employed contains 2–10 carbon atoms. In still other embodiments, the alkynyl group contains 2–8 carbon atoms. In still other embodiments, the alkynyl group contains 2–5 carbon atoms. Representative alkynyl groups include, but are not limited to, ethynyl, 2-propynyl

(propargyl), 1-propynyl, and the like, which may bear one or more substituents. Alkynyl group substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy,

heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted).

[0040] Exemplary carbon atom substituents include, but are not limited to, halogen,–CN, –NO ₂ ,–N ₃ ,–SO ₂ H,–SO ₃ H,–OH,–OR ^aa ,–ON(R ^bb ) ₂ ,–N(R ^bb ) ₂ ,–N(R ^bb ) ⁺

3 X ^– ,–N(OR ^cc )R ^bb ,– SH,–SR ^aa ,–SSR ^cc ,–C(=O)R ^aa ,–CO ₂ H,–CHO,–C(OR ^cc ) ₂ ,–CO ₂ R ^aa ,–OC(=O)R ^aa ,–

OCO ₂ R ^aa ,–C(=O)N(R ^bb ) ₂ ,–OC(=O)N(R ^bb ) ₂ ,–NR ^bb C(=O)R ^aa ,–NR ^bb CO ₂ R ^aa ,–

NR ^bb C(=O)N(R ^bb ) ₂ ,–C(=NR ^bb )R ^aa ,–C(=NR ^bb )OR ^aa ,–OC(=NR ^bb )R ^aa ,–OC(=NR ^bb )OR ^aa ,– C(=NR ^bb )N(R ^bb ) ₂ ,–OC(=NR ^bb )N(R ^bb ) ₂ ,–NR ^bb C(=NR ^bb )N(R ^bb ) ₂ ,–C(=O)NR ^bb SO ₂ R ^aa ,– NR ^bb SO ₂ R ^aa ,–SO ₂ N(R ^bb ) ₂ ,–SO ₂ R ^aa ,–SO ₂ OR ^aa ,–OSO ₂ R ^aa ,–S(=O)R ^aa ,–OS(=O)R ^aa ,– Si(R ^aa ) ₃ ,–OSi(R ^aa ) ₃ –C(=S)N(R ^bb ) ₂ ,–C(=O)SR ^aa ,–C(=S)SR ^aa ,–SC(=S)SR ^aa ,–SC(=O)SR ^aa , –OC(=O)SR ^aa ,–SC(=O)OR ^aa ,–SC(=O)R ^aa ,–P(=O) ₂ R ^aa ,–OP(=O) ₂ R ^aa ,–P(=O)(R ^aa ) ₂ ,– OP(=O)(R ^aa ) ₂ ,–OP(=O)(OR ^cc ) ₂ ,–P(=O) ₂ N(R ^bb ) ₂ ,–OP(=O) ₂ N(R ^bb ) ₂ ,–P(=O)(NR ^bb ) ₂ ,– OP(=O)(NR ^bb ) ₂ ,–NR ^bb P(=O)(OR ^cc ) ₂ ,–NR ^bb P(=O)(NR ^bb ) ₂ ,–P(R ^cc ) ₂ ,–P(R ^cc ) ₃ ,–OP(R ^cc ) ₂ ,– OP(R ^cc ) ₃ ,–B(R ^aa ) ₂ ,–B(OR ^cc ) ₂ ,–BR ^aa (OR ^cc ), C _1–10 alkyl, C _1–10 perhaloalkyl, C _2–10 alkenyl, C _2–10 alkynyl, C _3–10 carbocyclyl, 3–14 membered heterocyclyl, C _6–14 aryl, and 5–14

membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups;

or two geminal hydrogens on a carbon atom are replaced with the group =O, =S, =NN(R ^bb ) ₂ , =NNR ^bb C(=O)R ^aa , =NNR ^bb C(=O)OR ^aa , =NNR ^bb S(=O) ₂ R ^aa , =NR ^bb , or =NOR ^cc ; each instance of R ^aa is, independently, selected from C _1–10 alkyl, C _1–10 perhaloalkyl, C _2–10 alkenyl, C _2–10 alkynyl, C _3–10 carbocyclyl, 3–14 membered heterocyclyl, C _6–14 aryl, and 5–14 membered heteroaryl, or two R ^aa groups are joined to form a 3–14 membered

heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups;

each instance of R ^bb is, independently, selected from hydrogen,–OH,–OR ^aa ,–N(R ^cc ) ₂ , –CN,–C(=O)R ^aa ,–C(=O)N(R ^cc ) ₂ ,–CO ₂ R ^aa ,–SO ₂ R ^aa ,–C(=NR ^cc )OR ^aa ,–C(=NR ^cc )N(R ^cc ) ₂ ,– SO ₂ N(R ^cc ) ₂ ,–SO ₂ R ^cc ,–SO ₂ OR ^cc ,–SOR ^aa ,–C(=S)N(R ^cc ) ₂ ,–C(=O)SR ^cc ,–C(=S)SR ^cc ,– P(=O) ₂ R ^aa ,–P(=O)(R ^aa ) ₂ ,–P(=O) ₂ N(R ^cc ) ₂ ,–P(=O)(NR ^cc ) ₂ , C _1–10 alkyl, C _1–10 perhaloalkyl, C _{2– 10} alkenyl, C _2–10 alkynyl, C _3–10 carbocyclyl, 3–14 membered heterocyclyl, C _6–14 aryl, and 5– 14 membered heteroaryl, or two R ^bb groups are joined to form a 3–14 membered heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups;

each instance of R ^cc is, independently, selected from hydrogen, C _1–10 alkyl, C _1–10 perhaloalkyl, C _2–10 alkenyl, C _2–10 alkynyl, C _3–10 carbocyclyl, 3–14 membered heterocyclyl, C _6–14 aryl, and 5–14 membered heteroaryl, or two R ^cc groups are joined to form a 3–14 membered heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups;

each instance of R ^dd is, independently, selected from halogen,–CN,–NO ₂ ,–N ₃ ,– SO ₂ H,–SO ₃ H,–OH,–OR ^ee ,–ON(R ^ff ) ₂ ,–N(R ^ff ) ₂ ,–N(R ^ff ) ⁺

3 X ^– ,–N(OR ^ee )R ^ff ,–SH,–SR ^ee ,– SSR ^ee ,–C(=O)R ^ee ,–CO ₂ H,–CO ₂ R ^ee ,–OC(=O)R ^ee ,–OCO ₂ R ^ee ,–C(=O)N(R ^ff ) ₂ ,–

OC(=O)N(R ^ff ) ₂ ,–NR ^ff C(=O)R ^ee ,–NR ^ff CO ₂ R ^ee ,–NR ^ff C(=O)N(R ^ff ) ₂ ,–C(=NR ^ff )OR ^ee ,– OC(=NR ^ff )R ^ee ,–OC(=NR ^ff )OR ^ee ,–C(=NR ^ff )N(R ^ff ) ₂ ,–OC(=NR ^ff )N(R ^ff ) ₂ ,–

NR ^ff C(=NR ^ff )N(R ^ff ) ₂ ,–NR ^ff SO ₂ R ^ee ,–SO ₂ N(R ^ff ) ₂ ,–SO ₂ R ^ee ,–SO ₂ OR ^ee ,–OSO ₂ R ^ee ,–S(=O)R ^ee , –Si(R ^ee ) ₃ ,–OSi(R ^ee ) ₃ ,–C(=S)N(R ^ff ) ₂ ,–C(=O)SR ^ee ,–C(=S)SR ^ee ,–SC(=S)SR ^ee ,–P(=O) ₂ R ^ee ,– P(=O)(R ^ee ) ₂ ,–OP(=O)(R ^ee ) ₂ ,–OP(=O)(OR ^ee ) ₂ , C _1–6 alkyl, C _1–6 perhaloalkyl, C _2–6 alkenyl, C _{2– 6} alkynyl, C _3–10 carbocyclyl, 3–10 membered heterocyclyl, C _6–10 aryl, 5–10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups, or two geminal R ^dd substituents can be joined to form =O or =S;

each instance of R ^ee is, independently, selected from C _1–6 alkyl, C _1–6 perhaloalkyl, C _{2– 6} alkenyl, C _2–6 alkynyl, C _3–10 carbocyclyl, C _6–10 aryl, 3–10 membered heterocyclyl, and 3–10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups;

each instance of R ^ff is, independently, selected from hydrogen, C _1–6 alkyl, C _1–6 perhaloalkyl, C _2–6 alkenyl, C _2–6 alkynyl, C _3–10 carbocyclyl, 3–10 membered heterocyclyl, C _{6– 10} aryl and 5–10 membered heteroaryl, or two R ^ff groups are joined to form a 3–14 membered heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups; and each instance of R ^gg is, independently, halogen,–CN,–NO ₂ ,–N ₃ ,–SO ₂ H,–SO ₃ H,– OH,–OC _1–6 alkyl,–ON(C _1–6 alkyl) ₂ ,–N(C _1–6 alkyl) ₂ ,–N(C ⁺

1 _–6 alkyl) ₃ X ^– ,–NH(C _1–6 alkyl) ⁺ alkyl) ⁺ X ^– ,–NH ^{+ –}

2 X ^– ,–NH ₂ (C _{1–6 3} X ,–N(OC _1–6 alkyl)(C _1–6 alkyl),–N(OH)(C _1–6 alkyl), –NH(OH),–SH,–SC _1–6 alkyl,–SS(C _1–6 alkyl),–C(=O)(C _1–6 alkyl),–CO ₂ H,–CO ₂ (C _1–6 alkyl), –OC(=O)(C _1–6 alkyl),–OCO ₂ (C _1–6 alkyl),–C(=O)NH ₂ ,–C(=O)N(C _1–6 alkyl) ₂ ,–

OC(=O)NH(C _1–6 alkyl),–NHC(=O)( C _1–6 alkyl),–N(C _1–6 alkyl)C(=O)( C _1–6 alkyl),–

NHCO ₂ (C _1–6 alkyl),–NHC(=O)N(C _1–6 alkyl) ₂ ,–NHC(=O)NH(C _1–6 alkyl),–NHC(=O)NH ₂ ,– C(=NH)O(C _1–6 alkyl),–OC(=NH)(C _1–6 alkyl),–OC(=NH)OC _1–6 alkyl,–C(=NH)N(C _1–6 alkyl) ₂ ,–C(=NH)NH(C _1–6 alkyl),–C(=NH)NH ₂ ,–OC(=NH)N(C _1–6 alkyl) ₂ ,–OC(NH)NH(C _{1– 6} alkyl),–OC(NH)NH ₂ ,–NHC(NH)N(C _1–6 alkyl) ₂ ,–NHC(=NH)NH ₂ ,–NHSO ₂ (C _1–6 alkyl),– SO ₂ N(C _1–6 alkyl) ₂ ,–SO ₂ NH(C _1–6 alkyl),–SO ₂ NH ₂ ,–SO ₂ C _1–6 alkyl,–SO ₂ OC _1–6 alkyl,– OSO ₂ C _1–6 alkyl,–SOC _1–6 alkyl,–Si(C _1–6 alkyl) ₃ ,–OSi(C _1–6 alkyl) ₃ –C(=S)N(C _1–6 alkyl) ₂ , C(=S)NH(C _1–6 alkyl), C(=S)NH ₂ ,–C(=O)S(C _1–6 alkyl),–C(=S)SC _1–6 alkyl,–SC(=S)SC _1–6 alkyl,–P(=O) ₂ (C _1–6 alkyl),–P(=O)(C _1–6 alkyl) ₂ ,–OP(=O)(C _1–6 alkyl) ₂ ,–OP(=O)(OC _1–6 alkyl) ₂ , C _1–6 alkyl, C _1–6 perhaloalkyl, C _2–6 alkenyl, C _2–6 alkynyl, C _3–10 carbocyclyl, C _6–10 aryl, 3–10 membered heterocyclyl, 5–10 membered heteroaryl; or two geminal R ^gg substituents can be joined to form =O or =S; wherein X ^– is a counterion.

[0041] In some embodiments, exemplary carbon atom substituents include, but are not limited to, halogen,−CN,−NO ₂ ,−N ₃ ,−SO ₂ H,−SO ₃ H,−OH,−OR ^aa ,−ON(R ^bb ) ₂ ,−N(R ^bb ) ₂ , −N(R ^bb ) ⁺

3 X ⁻ ,−N(OR ^cc )R ^bb ,−SH,−SR ^aa ,−SSR ^cc ,−C(=O)R ^aa ,−CO ₂ H,−CHO,−C(OR ^cc ) ₂ , −CO ₂ R ^aa ,−OC(=O)R ^aa ,−OCO ₂ R ^aa ,−C(=O)N(R ^bb ) ₂ ,−OC(=O)N(R ^bb ) ₂ ,−NR ^bb C(=O)R ^aa , −NR ^bb CO ₂ R ^aa ,−NR ^bb C(=O)N(R ^bb ) ₂ ,−C(=NR ^bb )R ^aa ,−C(=NR ^bb )OR ^aa ,−OC(=NR ^bb )R ^aa , −OC(=NR ^bb )OR ^aa ,−C(=NR ^bb )N(R ^bb ) ₂ ,−OC(=NR ^bb )N(R ^bb ) ₂ ,−NR ^bb C(=NR ^bb )N(R ^bb ) ₂ , −C(=O)NR ^bb SO ₂ R ^aa ,−NR ^bb SO ₂ R ^aa ,−SO ₂ N(R ^bb ) ₂ ,−SO ₂ R ^aa ,−SO ₂ OR ^aa ,−OSO ₂ R ^aa , −S(=O)R ^aa ,−OS(=O)R ^aa ,−Si(R ^aa ) ₃ ,−OSi(R ^aa ) ₃ −C(=S)N(R ^bb ) ₂ ,−C(=O)SR ^aa ,−C(=S)SR ^aa , −SC(=S)SR ^aa ,−SC(=O)SR ^aa ,−OC(=O)SR ^aa ,−SC(=O)OR ^aa ,−SC(=O)R ^aa ,−P(=O)(R ^aa ) ₂ , −P(=O)(OR ^cc ) ₂ ,−OP(=O)(R ^aa ) ₂ ,−OP(=O)(OR ^cc ) ₂ ,−P(=O)(N(R ^bb ) ₂ ) ₂ ,−OP(=O)(N(R ^bb ) ₂ ) ₂ , −NR ^bb P(=O)(R ^aa ) ₂ ,−NR ^bb P(=O)(OR ^cc ) ₂ ,−NR ^bb P(=O)(N(R ^bb ) ₂ ) ₂ ,−P(R ^cc ) ₂ ,−P(OR ^cc ) ₂ , −P(R ^cc ) ⁺

3 X ⁻ ,−P(OR ^cc ) ⁺

3 X ⁻ ,−P(R ^cc ) ₄ ,−P(OR ^cc ) ₄ ,−OP(R ^cc ) ₂ ,−OP(R ^cc ) ⁺

3 X ⁻ ,−OP(OR ^cc ) ₂ , −OP(OR ^cc ) ⁺ X ⁻ ,−OP(R ^cc ) ^aa

3 ₄ ,−OP(OR ^cc ) ₄ ,−B(R ) ₂ ,−B(OR ^cc ) ₂ ,−BR ^aa (OR ^cc ), C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkenyl, C _2-10 alkynyl, heteroC _1-10 alkyl, heteroC _2-10 alkenyl, heteroC _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 membered heterocyclyl, C _6-14 aryl, and 5-14 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; wherein X ⁻ is a counterion;

or two geminal hydrogens on a carbon atom are replaced with the group =O, =S, =NN(R ^bb ) ₂ , =NNR ^bb C(=O)R ^aa , =NNR ^bb C(=O)OR ^aa , =NNR ^bb S(=O) ₂ R ^aa , =NR ^bb , or =NOR ^cc ; each instance of R ^aa is, independently, selected from C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkenyl, C _2-10 alkynyl, heteroC _1-10 alkyl, heteroC _2-10 alkenyl, heteroC _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 membered heterocyclyl, C _6-14 aryl, and 5-14 membered heteroaryl, or two R ^aa groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups;

each instance of R ^bb is, independently, selected from hydrogen,−OH,−OR ^aa , −N(R ^cc ) ₂ ,−CN,−C(=O)R ^aa ,−C(=O)N(R ^cc ) ₂ ,−CO ₂ R ^aa ,−SO ₂ R ^aa ,−C(=NR ^cc )OR ^aa , −C(=NR ^cc )N(R ^cc ) ₂ ,−SO ₂ N(R ^cc ) ₂ ,−SO ₂ R ^cc ,−SO ₂ OR ^cc ,−SOR ^aa ,−C(=S)N(R ^cc ) ₂ ,−C(=O)SR ^cc , −C(=S)SR ^cc ,−P(=O)(R ^aa ) ₂ ,−P(=O)(OR ^cc ) ₂ ,−P(=O)(N(R ^cc ) ₂ ) ₂ , C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkenyl, C _2-10 alkynyl, heteroC _1-10 alkyl, heteroC _2-10 alkenyl, heteroC _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 membered heterocyclyl, C _6-14 aryl, and 5-14 membered heteroaryl, or two R ^bb groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; wherein X ⁻ is a counterion;

each instance of R ^cc is, independently, selected from hydrogen, C _1-10 alkyl, C _1-10 perhaloalkyl, C _2-10 alkenyl, C _2-10 alkynyl, heteroC _1-10 alkyl, heteroC _2-10 alkenyl, heteroC _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 membered heterocyclyl, C _6-14 aryl, and 5-14 membered heteroaryl, or two R ^cc groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups;

each instance of R ^dd is, independently, selected from halogen,−CN,−NO ₂ ,−N ₃ , −SO ₂ H,−SO ₃ H,−OH,−OR ^ee ,−ON(R ^ff ) ₂ ,−N(R ^ff ) ₂ ,−N(R ^ff ) ⁺

3 X ⁻ ,−N(OR ^ee )R ^ff ,−SH,−SR ^ee , −SSR ^ee ,−C(=O)R ^ee ,−CO ₂ H,−CO ₂ R ^ee ,−OC(=O)R ^ee ,−OCO ₂ R ^ee ,−C(=O)N(R ^ff ) ₂ ,

−OC(=O)N(R ^ff ) ₂ ,−NR ^ff C(=O)R ^ee ,−NR ^ff CO ₂ R ^ee ,−NR ^ff C(=O)N(R ^ff ) ₂ ,−C(=NR ^ff )OR ^ee , −OC(=NR ^ff )R ^ee ,−OC(=NR ^ff )OR ^ee ,−C(=NR ^ff )N(R ^ff ) ₂ ,−OC(=NR ^ff )N(R ^ff ) ₂ ,

−NR ^ff C(=NR ^ff )N(R ^ff ) ₂ ,−NR ^ff SO ₂ R ^ee ,−SO ₂ N(R ^ff ) ₂ ,−SO ₂ R ^ee ,−SO ₂ OR ^ee ,−OSO ₂ R ^ee , −S(=O)R ^ee ,−Si(R ^ee ) ₃ ,−OSi(R ^ee ) ₃ ,−C(=S)N(R ^ff ) ₂ ,−C(=O)SR ^ee ,−C(=S)SR ^ee ,−SC(=S)SR ^ee , −P(=O)(OR ^ee ) ₂ ,−P(=O)(R ^ee ) ₂ ,−OP(=O)(R ^ee ) ₂ ,−OP(=O)(OR ^ee ) ₂ , C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, heteroC _1-6 alkyl, heteroC _2-6 alkenyl, heteroC _2-6 alkynyl, C _3-10 carbocyclyl, 3-10 membered heterocyclyl, C _6-10 aryl, 5-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups, or two geminal R ^dd substituents can be joined to form =O or =S; wherein X ⁻ is a counterion;

each instance of R ^ee is, independently, selected from C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, heteroC _1-6 alkyl, heteroC _2-6 alkenyl, heteroC _2-6 alkynyl, C _3-10

carbocyclyl, C _6-10 aryl, 3-10 membered heterocyclyl, and 3-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups;

each instance of R ^ff is, independently, selected from hydrogen, C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, heteroC _1-6 alkyl, heteroC _2-6 alkenyl, heteroC _2-6 alkynyl, C _3-10 carbocyclyl, 3-10 membered heterocyclyl, C _6-10 aryl and 5-10 membered heteroaryl, or two R ^ff groups are joined to form a 3-10 membered heterocyclyl or 5-10 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl,

heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups; and

each instance of R ^gg is, independently, halogen,−CN,−NO ₂ ,−N ₃ ,−SO ₂ H,−SO ₃ H, −OH,−OC _1-6 alkyl,−ON(C _1-6 alkyl) ₂ ,−N(C _1-6 alkyl) ₂ ,−N(C _1-6 alkyl) ⁺

3 X ⁻ ,−NH(C _1-6 alkyl) ⁺

2 X ⁻ ,−NH ₂ (C _1-6 alkyl) ⁺ X ⁻ ,−NH ⁺

3 X ⁻ ,−N(OC _1-6 alkyl)(C _1-6 alkyl),−N(OH)(C _1-6 alkyl), −NH(OH),−SH,−SC _1-6 alkyl,−SS(C _1-6 alkyl),−C(=O)(C _1-6 alkyl),−CO ₂ H,−CO ₂ (C _1-6 alkyl),−OC(=O)(C _1-6 alkyl),−OCO ₂ (C _1-6 alkyl),−C(=O)NH ₂ ,−C(=O)N(C _1-6 alkyl) ₂ , −OC(=O)NH(C _1-6 alkyl),−NHC(=O)( C _1-6 alkyl),−N(C _1-6 alkyl)C(=O)( C _1-6 alkyl), −NHCO ₂ (C _1-6 alkyl),−NHC(=O)N(C _1-6 alkyl) ₂ ,−NHC(=O)NH(C _1-6 alkyl),−NHC(=O)NH ₂ , −C(=NH)O(C _1-6 alkyl),−OC(=NH)(C _1-6 alkyl),−OC(=NH)OC _1-6 alkyl,−C(=NH)N(C _1-6 alkyl) ₂ ,−C(=NH)NH(C _1-6 alkyl),−C(=NH)NH ₂ ,−OC(=NH)N(C _1-6 alkyl) ₂ ,−OC(NH)NH(C _{1- 6} alkyl),−OC(NH)NH ₂ ,−NHC(NH)N(C _1-6 alkyl) ₂ ,−NHC(=NH)NH ₂ ,−NHSO ₂ (C _1-6 alkyl), −SO ₂ N(C _1-6 alkyl) ₂ ,−SO ₂ NH(C _1-6 alkyl),−SO ₂ NH ₂ ,−SO ₂ C _1-6 alkyl,−SO ₂ OC _1-6 alkyl, −OSO ₂ C _1-6 alkyl,−SOC _1-6 alkyl,−Si(C _1-6 alkyl) ₃ ,−OSi(C _1-6 alkyl) ₃ −C(=S)N(C _1-6 alkyl) ₂ , C(=S)NH(C _1-6 alkyl), C(=S)NH ₂ ,−C(=O)S(C _1-6 alkyl),−C(=S)SC _1-6 alkyl,−SC(=S)SC _1-6 alkyl,−P(=O)(OC _1-6 alkyl) ₂ ,−P(=O)(C _1-6 alkyl) ₂ ,−OP(=O)(C _1-6 alkyl) ₂ ,−OP(=O)(OC _1-6 alkyl) ₂ , C _1-6 alkyl, C _1-6 perhaloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, heteroC _1-6 alkyl, heteroC _{2- 6} alkenyl, heteroC _2-6 alkynyl, C _3-10 carbocyclyl, C _6-10 aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl; or two geminal R ^gg substituents can be joined to form =O or =S;

wherein X ⁻ is a counterion.

[0042] The term“amino” refers to a group of the formula (–NH ₂ ). A“substituted amino” refers either to a mono-substituted amine (–NHR ^h ) of a disubstituted amine (–NR ^h

2), wherein the R ^h substituent is any substituent as described herein that results in the formation of a stable moiety (e.g., a suitable amino protecting group; aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, amino, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino,

heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy,

heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted). In certain embodiments, the R ^h substituents of the di- substituted amino group(–NR ^h

2) form a 5- to 6-membered heterocyclic ring.

[0043] The term“alkoxy” refers to a“substituted hydroxyl” of the formula (–OR ⁱ ), wherein R ⁱ is an optionally substituted alkyl group as defined herein, and the oxygen moiety is directly attached to the parent molecule.

[0044] The term“alkylthioxy” refers to a“substituted thiol” of the formula (–SR ^r ), wherein R ^r is an optionally substituted alkyl group as defined herein, and the sulfur moiety is directly attached to the parent molecule.

[0045] The term“alkylamino” refers to a“substituted amino” of the formula (–NR ^h

2), wherein R ^h is, independently, a hydrogen or an optionally substituted alkyl group as defined herein, and the nitrogen moiety is directly attached to the parent molecule.

[0046] The term“aryl” refer to stable aromatic mono- or polycyclic ring system having 3–20 ring atoms, of which all the ring atoms are carbon, and which may be substituted or unsubstituted. In certain embodiments of the present invention,“aryl” refers to a mono, bi, or tricyclic C ₄ –C ₂₀ aromatic ring system having one, two, or three aromatic rings which include, but not limited to, phenyl, biphenyl, naphthyl, and the like, which may bear one or more substituents. Aryl substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted).

[0047] The term“arylalkyl” refers to an aryl substituted alkyl group, wherein the terms “aryl” and“alkyl” are defined herein, and wherein the aryl group is attached to the alkyl group, which in turn is attached to the parent molecule. Exemplary arylalkyl groups are benzyl and phenethyl.

[0048] The term“aryloxy” refers to a“substituted hydroxyl” of the formula (–OR ⁱ ), wherein R ⁱ is an optionally substituted aryl group as defined herein, and the oxygen moiety is directly attached to the parent molecule.

[0049] The term“arylamino,” refers to a“substituted amino” of the formula (–NR ^h

2), wherein R ^h is, independently, a hydrogen or an optionally substituted aryl group as defined herein, and the nitrogen moiety is directly attached to the parent molecule.

[0050] The term“arylthioxy” refers to a“substituted thiol” of the formula (–SR ^r ), wherein R ^r is an optionally substituted aryl group as defined herein, and the sulfur moiety is directly attached to the parent molecule.

[0051] The terms“halo” and“halogen” refer to an atom selected from fluorine (fluoro,– F), chlorine (chloro,–Cl), bromine (bromo,–Br), and iodine (iodo,–I).

[0052] The term“heteroaliphatic” refers to an aliphatic moiety, as defined herein, which includes both saturated and unsaturated, nonaromatic, straight chain (i.e., unbranched), branched, acyclic, cyclic (i.e., heterocyclic), or polycyclic hydrocarbons, which are optionally substituted with one or more functional groups, and that contain one or more oxygen, sulfur, nitrogen, phosphorus, or silicon atoms, e.g., in place of carbon atoms. In certain

embodiments, heteroaliphatic moieties are substituted by independent replacement of one or more of the hydrogen atoms thereon with one or more substituents. As will be appreciated by one of ordinary skill in the art,“heteroaliphatic” is intended herein to include, but is not limited to, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocycloalkyl, heterocycloalkenyl, and heterocycloalkynyl moieties. Thus, the term“heteroaliphatic” includes the terms “heteroalkyl,”“heteroalkenyl”,“heteroalkynyl”, and the like. Furthermore, the terms “heteroalkyl”,“heteroalkenyl”,“heteroalkynyl”, and the like encompass both substituted and unsubstituted groups. In certain embodiments,“heteroaliphatic” is used to indicate those heteroaliphatic groups (cyclic, acyclic, substituted, unsubstituted, branched or unbranched) having 1–20 carbon atoms. Heteroaliphatic group substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, sulfinyl, sulfonyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino,

heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy,

heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted).

[0053] The term“heteroalkyl” refers to an alkyl moiety, as defined herein, which contain one or more oxygen, sulfur, nitrogen, phosphorus, or silicon atoms, e.g., in place of carbon atoms.

[0054] The term“heteroalkenyl” refers to an alkenyl moiety, as defined herein, which contain one or more oxygen, sulfur, nitrogen, phosphorus, or silicon atoms, e.g., in place of carbon atoms.

[0055] The term“heteroalkynyl” refers to an alkynyl moiety, as defined herein, which contain one or more oxygen, sulfur, nitrogen, phosphorus, or silicon atoms, e.g., in place of carbon atoms.

[0056] The term“heteroalkylamino” refers to a“substituted amino” of the formula (– NR ^h

2), wherein R ^h is, independently, a hydrogen or an optionally substituted heteroalkyl group, as defined herein, and the nitrogen moiety is directly attached to the parent molecule.

[0057] The term“heteroalkyloxy” refers to a“substituted hydroxyl” of the formula (– OR ⁱ ), wherein R ⁱ is an optionally substituted heteroalkyl group, as defined herein, and the oxygen moiety is directly attached to the parent molecule.

[0058] The term“heteroalkylthioxy” refers to a“substituted thiol” of the formula (–SR ^r ), wherein R ^r is an optionally substituted heteroalkyl group, as defined herein, and the sulfur moiety is directly attached to the parent molecule.

[0059] The term“carbocyclyl” or“carbocyclic” refers to a radical of a non–aromatic cyclic hydrocarbon group having from 3 to 14 ring carbon atoms (“C _3–14 carbocyclyl”) and zero heteroatoms in the non–aromatic ring system. In some embodiments, a carbocyclyl group has 3 to 10 ring carbon atoms (“C _3–10 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 8 ring carbon atoms (“C _3–8 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 7 ring carbon atoms (“C _3–7 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 6 ring carbon atoms (“C _3–6 carbocyclyl”). In some embodiments, a carbocyclyl group has 4 to 6 ring carbon atoms (“C _4–6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 6 ring carbon atoms (“C _5–6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 10 ring carbon atoms (“C _5–10 carbocyclyl”). Exemplary C _3–6 carbocyclyl groups include, without limitation, cyclopropyl (C ₃ ), cyclopropenyl (C ₃ ), cyclobutyl (C ₄ ), cyclobutenyl (C ₄ ), cyclopentyl (C ₅ ), cyclopentenyl (C ₅ ), cyclohexyl (C ₆ ), cyclohexenyl (C ₆ ), cyclohexadienyl (C ₆ ), and the like. Exemplary C _3–8 carbocyclyl groups include, without limitation, the aforementioned C _3–6 carbocyclyl groups as well as cycloheptyl (C ₇ ), cycloheptenyl (C ₇ ), cycloheptadienyl (C ₇ ), cycloheptatrienyl (C ₇ ), cyclooctyl (C ₈ ), cyclooctenyl (C ₈ ), bicyclo[2.2.1]heptanyl (C ₇ ), bicyclo[2.2.2]octanyl (C ₈ ), and the like. Exemplary C _3–10 carbocyclyl groups include, without limitation, the

aforementioned C _3–8 carbocyclyl groups as well as cyclononyl (C ₉ ), cyclononenyl (C ₉ ), cyclodecyl (C ₁₀ ), cyclodecenyl (C ₁₀ ), octahydro–1H–indenyl (C ₉ ), decahydronaphthalenyl (C ₁₀ ), spiro[4.5]decanyl (C ₁₀ ), and the like. As the foregoing examples illustrate, in certain embodiments, the carbocyclyl group is either monocyclic (“monocyclic carbocyclyl”) or polycyclic (e.g., containing a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic carbocyclyl”) or tricyclic system (“tricyclic carbocyclyl”)) and can be saturated or can contain one or more carbon–carbon double or triple bonds.“Carbocyclyl” also includes ring systems wherein the carbocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the carbocyclic ring system. Unless otherwise specified, each instance of a carbocyclyl group is independently unsubstituted (an“unsubstituted carbocyclyl”) or substituted (a“substituted carbocyclyl”) with one or more substituents. In certain embodiments, the carbocyclyl group is an unsubstituted C _3–14 carbocyclyl. In certain embodiments, the carbocyclyl group is a substituted C _3–14 carbocyclyl.

[0060] In some embodiments,“carbocyclyl” is a monocyclic, saturated carbocyclyl group having from 3 to 14 ring carbon atoms (“C _3–14 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 10 ring carbon atoms (“C _3–10 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms (“C _3–8 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms (“C _3–6 cycloalkyl”). In some embodiments, a cycloalkyl group has 4 to 6 ring carbon atoms (“C _4–6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms (“C _5–6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms (“C _5–10 cycloalkyl”). Examples of C _5–6 cycloalkyl groups include cyclopentyl (C ₅ ) and cyclohexyl (C ₅ ). Examples of C _3–6 cycloalkyl groups include the aforementioned C _5–6 cycloalkyl groups as well as cyclopropyl (C ₃ ) and cyclobutyl (C ₄ ). Examples of C _3–8 cycloalkyl groups include the aforementioned C _3–6 cycloalkyl groups as well as cycloheptyl (C ₇ ) and cyclooctyl (C ₈ ). Unless otherwise specified, each instance of a cycloalkyl group is independently unsubstituted (an“unsubstituted cycloalkyl”) or substituted (a“substituted cycloalkyl”) with one or more substituents. In certain embodiments, the cycloalkyl group is an unsubstituted C _3–14 cycloalkyl. In certain embodiments, the cycloalkyl group is a substituted C _3–14 cycloalkyl.

[0061] The term“heterocyclic,”“heterocycles,” or“heterocyclyl” refers to a cyclic heteroaliphatic group. A heterocyclic group refers to a non-aromatic, partially unsaturated or fully saturated, 3- to 12-membered ring system, which includes single rings of 3 to 8 atoms in size, and bi- and tri-cyclic ring systems which may include aromatic five- or six-membered aryl or heteroaryl groups fused to a non-aromatic ring. These heterocyclic rings include those having from one to three heteroatoms independently selected from oxygen, sulfur, and nitrogen, in which the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. In certain embodiments, the term heterocyclic refers to a non-aromatic 5-, 6-, or 7-membered ring or polycyclic group wherein at least one ring atom is a heteroatom selected from O, S, and N (wherein the nitrogen and sulfur heteroatoms may be optionally oxidized), and the remaining ring atoms are carbon, the radical being joined to the rest of the molecule via any of the ring atoms. Heterocyclyl groups include, but are not limited to, a bi- or tri-cyclic group, comprising fused five, six, or seven- membered rings having between one and three heteroatoms independently selected from the oxygen, sulfur, and nitrogen, wherein (i) each 5-membered ring has 0 to 2 double bonds, each 6-membered ring has 0 to 2 double bonds, and each 7-membered ring has 0 to 3 double bonds, (ii) the nitrogen and sulfur heteroatoms may be optionally oxidized, (iii) the nitrogen heteroatom may optionally be quaternized, and (iv) any of the above heterocyclic rings may be fused to an aryl or heteroaryl ring. Exemplary heterocycles include azacyclopropanyl, azacyclobutanyl, 1,3-diazatidinyl, piperidinyl, piperazinyl, azocanyl, thiaranyl, thietanyl, tetrahydrothiophenyl, dithiolanyl, thiacyclohexanyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropuranyl, dioxanyl, oxathiolanyl, morpholinyl, thioxanyl, tetrahydronaphthyl, and the like, which may bear one or more substituents. Substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, sulfinyl, sulfonyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted).

[0062] The term“heteroaryl” refer to stable aromatic mono- or polycyclic ring system having 3-20 ring atoms, of which one ring atom is selected from S, O, and N; zero, one, or two ring atoms are additional heteroatoms independently selected from S, O, and N; and the remaining ring atoms are carbon, the radical being joined to the rest of the molecule via any of the ring atoms. Exemplary heteroaryls include, but are not limited to pyrrolyl, pyrazolyl, imidazolyl, pyridinyl (pyridyl), pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, tetrazinyl, pyyrolizinyl, indolyl, quinolinyl, isoquinolinyl, benzoimidazolyl, indazolyl, quinolinyl, isoquinolinyl, quinolizinyl, cinnolinyl, quinazolynyl, phthalazinyl, naphthridinyl, quinoxalinyl, thiophenyl, thianaphthenyl, furanyl, benzofuranyl, benzothiazolyl, thiazolynyl, isothiazolyl, thiadiazolynyl, oxazolyl, isoxazolyl, oxadiaziolyl, oxadiaziolyl, and the like, which may bear one or more substituents. Heteroaryl substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, sulfinyl, sulfonyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted).

[0063] The term“heteroarylamino” refers to a“substituted amino” of the (–NR ^h

2), wherein R ^h is, independently, hydrogen or an optionally substituted heteroaryl group, as defined herein, and the nitrogen moiety is directly attached to the parent molecule.

[0064] The term“heteroaryloxy” refers to a“substituted hydroxyl” of the formula (– OR ⁱ ), wherein R ⁱ is an optionally substituted heteroaryl group, as defined herein, and the oxygen moiety is directly attached to the parent molecule.

[0065] The term“heteroarylthioxy” refers to a“substituted thiol” of the formula (–SR ^r ), wherein R ^r is an optionally substituted heteroaryl group, as defined herein, and the sulfur moiety is directly attached to the parent molecule.

[0066] The term“hydroxy” or“hydroxyl” refers to a group of the formula (–OH). A “substituted hydroxyl” refers to a group of the formula (–OR ⁱ ), wherein R ⁱ can be any substituent which results in a stable moiety (e.g., a suitable hydroxyl protecting group; aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, nitro, alkylaryl, arylalkyl, and the like, each of which may or may not be further substituted).

[0067] The term“imino” refers to a group of the formula (=NR ^r ), wherein R ^r corresponds to hydrogen or any substituent as described herein, that results in the formation of a stable moiety (for example, a suitable amino protecting group; aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, amino, hydroxyl, alkylaryl, arylalkyl, and the like, each of which may or may not be further substituted). In certain embodiments, imino refers to =NH wherein R ^r is hydrogen.

[0068] The term“nitro” refers to a group of the formula (–NO ₂ ).

[0069] The term“oxo” refers to a group of the formula (=O).

[0070] A“protecting group” is well known in the art and include those described in detail in Greene’s Protective Groups in Organic Synthesis, P. G. M. Wuts and T. W. Greene, 4 ^th edition, Wiley-Interscience, 2006, the entirety of which is incorporated herein by reference. Suitable“amino-protecting groups” (also referred to as“nitrogen protecting groups”) include methyl carbamate, ethyl carbamante, 9-fluorenylmethyl carbamate (Fmoc), 9-(2- sulfo)fluorenylmethyl carbamate, 9-(2,7-dibromo)fluoroenylmethyl carbamate, 2,7-di-t-butyl- [9-(10,10-dioxo-10,10,10,10-tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4- methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2- trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), 1-(1-adamantyl)-1- methylethyl carbamate (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2- dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate

(TCBOC), 1-methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1-(3,5-di-t-butylphenyl)-1- methylethyl carbamate (t-Bumeoc), 2-(2′- and 4′-pyridyl)ethyl carbamate (Pyoc), 2-(N,N- dicyclohexylcarboxamido)ethyl carbamate, t-butyl carbamate (BOC or Boc), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithio carbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitobenzyl carbamate, p-bromobenzyl carbamate, p- chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3- dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4- dimethylthiophenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2- triphenylphosphonioisopropyl carbamate (Ppoc), 1,1-dimethyl-2-cyanoethyl carbamate, m- chloro-p-acyloxybenzyl carbamate, p-(dihydroxyboryl)benzyl carbamate, 5- benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6-chromonylmethyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4- dimethoxy-6-nitrobenzyl carbamate, phenyl(o-nitrophenyl)methyl carbamate, phenothiazinyl- (10)-carbonyl derivative, N′-p-toluenesulfonylaminocarbonyl derivative, N′- phenylaminothiocarbonyl derivative, t-amyl carbamate, S-benzyl thiocarbamate, p- cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p-decyloxybenzyl carbamate, 2,2-dimethoxycarbonylvinyl carbamate, o-(N,N-dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl-3-(N,N- dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2- pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isoborynl carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p′-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1-methylcyclohexyl carbamate, 1-methyl-1- cyclopropylmethyl carbamate, 1-methyl-1-(3,5-dimethoxyphenyl)ethyl carbamate, 1-methyl- 1-(p-phenylazophenyl)ethyl carbamate, 1-methyl-1-phenylethyl carbamate, 1-methyl-1-(4- pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t- butylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, 2,4,6-trimethylbenzyl carbamate, formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropanamide, picolinamide, 3-pyridylcarboxamide, N- benzoylphenylalanyl derivative, benzamide, p-phenylbenzamide, o-nitophenylacetamide, o- nitrophenoxyacetamide, acetoacetamide, (N′-dithiobenzyloxycarbonylamino)acetamide, 3-(p- hydroxyphenyl)propanamide, 3-(o-nitrophenyl)propanamide, 2-methyl-2-(o- nitrophenoxy)propanamide, 2-methyl-2-(o-phenylazophenoxy)propanamide, 4- chlorobutanamide, 3-methyl-3-nitrobutanamide, o-nitrocinnamide, N-acetylmethionine derivative, o-nitrobenzamide, o-(benzoyloxymethyl)benzamide, 4,5-diphenyl-3-oxazolin-2- one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3-diphenylmaleimide, N-2,5- dimethylpyrrole, N-1,1,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5- substituted 1,3-dimethyl-1,3,5-triazacyclohexan-2-one, 5-substituted 1,3-dibenzyl-1,3,5- triazacyclohexan-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl-4- nitro-2-oxo-3-pyroolin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N-di(4- methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N- [(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N-2,7- dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-picolylamino N′- oxide, N-1,1-dimethylthiomethyleneamine, N-benzylideneamine, N-p- methoxybenzylideneamine, N-diphenylmethyleneamine, N-[(2- pyridyl)mesityl]methyleneamine, N-(N′,N′-dimethylaminomethylene)amine, N,N′- isopropylidenediamine, N-p-nitrobenzylideneamine, N-salicylideneamine, N-5- chlorosalicylideneamine, N-(5-chloro-2-hydroxyphenyl)phenylmethyleneamine, N- cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)amine, N-borane derivative, N-diphenylborinic acid derivative, N-[phenyl(pentacarbonylchromium- or

tungsten)carbonyl]amine, N-copper chelate, N-zinc chelate, N-nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkyl phosphoramidates, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4- dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4- methoxybenzenesulfenamide, triphenylmethylsulfenamide, 3-nitropyridinesulfenamide (Npys), p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6,-trimethyl-4- methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6- dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4- methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6- trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β- trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4′,8′- dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide,

trifluoromethylsulfonamide, and phenacylsulfonamide.

[0071] A“hydroxyl protecting group” (also referred to as an“oxygen protecting group”) is well known in the art and includes those described in detail in Greene (1999). Suitable hydroxyl protecting groups include methyl, methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2- methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2- (trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3- bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4- methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiopyranyl, 4- methoxytetrahydrothiopyranyl S,S-dioxide, 1-[(2-chloro-4-methyl)phenyl]-4- methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanobenzo furan-2-yl, 1-ethoxyethyl, 1- (2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1- benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-(phenylselenyl)ethyl, t- butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p- cyanobenzyl, p-phenylbenzyl, 2-picolyl, 4-picolyl, 3-methyl-2-picolyl N-oxido,

diphenylmethyl, p,p′-dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, α- naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p- methoxyphenyl)phenylmethyl, tri(p-methoxyphenyl)methyl, 4-(4′- bromophenacyloxyphenyl)diphenylmethyl, 4,4′,4″-tris(4,5- dichlorophthalimidophenyl)methyl, 4,4′,4″-tris(levulinoyloxyphenyl)methyl, 4,4′,4″- tris(benzoyloxyphenyl)methyl, 3-(imidazol-1-yl)bis(4′,4″-dimethoxyphenyl)methyl, 1,1- bis(4-methoxyphenyl)-1′-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10- oxo)anthryl, 1,3-benzodithiolan-2-yl, benzisothiazolyl S,S-dioxido, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS),

diethylisopropylsilyl (DEIPS), dimethylthexylsilyl, t-butyldimethylsilyl (TBDMS), t- butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl,

diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4- oxopentanoate (levulinate), 4,4-(ethylenedithio)pentanoate (levulinoyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6- trimethylbenzoate (mesitoate), alkyl methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), alkyl ethyl carbonate, alkyl 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl) ethyl carbonate (Psec), 2-(triphenylphosphonio) ethyl carbonate (Peoc), alkyl isobutyl carbonate, alkyl vinyl carbonate alkyl allyl carbonate, alkyl p-nitrophenyl carbonate, alkyl benzyl carbonate, alkyl p-methoxybenzyl carbonate, alkyl 3,4-dimethoxybenzyl carbonate, alkyl o-nitrobenzyl carbonate, alkyl p-nitrobenzyl carbonate, alkyl S-benzyl thiocarbonate, 4-ethoxy-1-napththyl carbonate, methyl

dithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylpentanoate, o- (dibromomethyl)benzoate, 2-formylbenzenesulfonate, 2-(methylthiomethoxy)ethyl, 4- (methylthiomethoxy)butyrate, 2-(methylthiomethoxymethyl)benzoate, 2,6-dichloro-4- methylphenoxyacetate, 2,6-dichloro-4-(1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(1,1- dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E)-2- methyl-2-butenoate, o-(methoxycarbonyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N′,N′- tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts). For protecting 1,2- or 1,3-diols, protecting groups include methylene acetal, ethylidene acetal, 1-t-butylethylidene ketal, 1-phenylethylidene ketal, (4- methoxyphenyl)ethylidene acetal, 2,2,2-trichloroethylidene acetal, acetonide,

cyclopentylidene ketal, cyclohexylidene ketal, cycloheptylidene ketal, benzylidene acetal, p- methoxybenzylidene acetal, 2,4-dimethoxybenzylidene ketal, 3,4-dimethoxybenzylidene acetal, 2-nitrobenzylidene acetal, methoxymethylene acetal, ethoxymethylene acetal, dimethoxymethylene ortho ester, 1-methoxyethylidene ortho ester, 1-ethoxyethylidine ortho ester, 1,2-dimethoxyethylidene ortho ester, α-methoxybenzylidene ortho ester, 1-(N,N- dimethylamino)ethylidene derivative, α-(N,N′-dimethylamino)benzylidene derivative, 2- oxacyclopentylidene ortho ester, di-t-butylsilylene group (DTBS), 1,3-(1,1,3,3- tetraisopropyldisiloxanylidene) derivative (TIPDS), tetra-t-butoxydisiloxane-1,3-diylidene derivative (TBDS), cyclic carbonates, cyclic boronates, ethyl boronate, and phenyl boronate.

[0072] In certain embodiments, the substituent present on an sulfur atom is a sulfur protecting group (also referred to as a“thiol protecting group”). Sulfur protecting groups include, but are not limited to,–R ^aa ,–N(R ^bb ) ₂ ,–C(=O)SR ^aa ,–C(=O)R ^aa ,–CO ₂ R ^aa ,–

C(=O)N(R ^bb ) ₂ ,–C(=NR ^bb )R ^aa ,–C(=NR ^bb )OR ^aa ,–C(=NR ^bb )N(R ^bb ) ₂ ,–S(=O)R ^aa ,–SO ₂ R ^aa ,– Si(R ^aa ) _3, –P(R ^cc ) ₂ ,–P(R ^cc ) ₃ ,–P(=O) ₂ R ^aa ,–P(=O)(R ^aa ) ₂ ,–P(=O)(OR ^cc ) ₂ ,–P(=O) ₂ N(R ^bb ) ₂ , and– P(=O)(NR ^bb ) ₂ , wherein R ^aa , R ^bb , and R ^cc are as defined herein. In some embodiments, sulfur protecting groups include, but are not limited to,−R ^aa ,−N(R ^bb ) ₂ ,−C(=O)SR ^aa ,−C(=O)R ^aa , −CO ₂ R ^aa ,−C(=O)N(R ^bb ) ₂ ,−C(=NR ^bb )R ^aa ,−C(=NR ^bb )OR ^aa ,−C(=NR ^bb )N(R ^bb ) ₂ ,−S(=O)R ^aa , −SO ₂ R ^aa ,−Si(R ^aa ) ₃ ,−P(R ^cc ) ₂ ,−P(R ^cc ) ⁺

3 X ⁻ ,−P(OR ^cc ) ₂ ,−P(OR ^cc ) ⁺

3 X ⁻ ,−P(=O)(R ^aa ) ₂ , −P(=O)(OR ^cc ) ₂ , and−P(=O)(N(R ^bb ) ₂ ) ₂ , wherein R ^aa , R ^bb , and R ^cc are as defined herein. Sulfur protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3 ^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. [0073] The term“carbohydrate” or“saccharide” refers to an aldehydic or ketonic derivative of polyhydric alcohols. Carbohydrates include compounds with relatively small molecules (e.g., sugars) as well as macromolecular or polymeric substances (e.g., starch, glycogen, and cellulose polysaccharides). The term“sugar” refers to monosaccharides, disaccharides, or polysaccharides. Monosaccharides are the simplest carbohydrates in that they cannot be hydrolyzed to smaller carbohydrates. Most monosaccharides can be represented by the general formula C _y H _2y O _y (e.g., C ₆ H ₁₂ O ₆ (a hexose such as glucose)), wherein y is an integer equal to or greater than 3. Certain polyhydric alcohols not represented by the general formula described above may also be considered monosaccharides. For example, deoxyribose is of the formula C ₅ H ₁₀ O ₄ and is a monosaccharide. Monosaccharides usually consist of five or six carbon atoms and are referred to as pentoses and hexoses, receptively. If the monosaccharide contains an aldehyde it is referred to as an aldose; and if it contains a ketone, it is referred to as a ketose. Monosaccharides may also consist of three, four, or seven carbon atoms in an aldose or ketose form and are referred to as trioses, tetroses, and heptoses, respectively. Glyceraldehyde and dihydroxyacetone are considered to be aldotriose and ketotriose sugars, respectively. Examples of aldotetrose sugars include erythrose and threose; and ketotetrose sugars include erythrulose. Aldopentose sugars include ribose, arabinose, xylose, and lyxose; and ketopentose sugars include ribulose, arabulose, xylulose, and lyxulose. Examples of aldohexose sugars include glucose (for example, dextrose), mannose, galactose, allose, altrose, talose, gulose, and idose; and ketohexose sugars include fructose, psicose, sorbose, and tagatose. Ketoheptose sugars include sedoheptulose. Each carbon atom of a monosaccharide bearing a hydroxyl group (–OH), with the exception of the first and last carbons, is asymmetric, making the carbon atom a stereocenter with two possible configurations (R or S). Because of this asymmetry, a number of isomers may exist for any given monosaccharide formula. The aldohexose ^D -glucose, for example, has the formula C ₆ H ₁₂ O ₆ , of which all but two of its six carbons atoms are stereogenic, making D-glucose one of the 16 (i.e., 2 ⁴ ) possible stereoisomers. The assignment of ^D or ^L is made according to the orientation of the asymmetric carbon furthest from the carbonyl group: in a standard Fischer projection if the hydroxyl group is on the right the molecule is a D sugar, otherwise it is an L sugar. The aldehyde or ketone group of a straight- chain monosaccharide will react reversibly with a hydroxyl group on a different carbon atom to form a hemiacetal or hemiketal, forming a heterocyclic ring with an oxygen bridge between two carbon atoms. Rings with five and six atoms are called furanose and pyranose forms, respectively, and exist in equilibrium with the straight-chain form. During the conversion from the straight-chain form to the cyclic form, the carbon atom containing the carbonyl oxygen, called the anomeric carbon, becomes a stereogenic center with two possible configurations: the oxygen atom may take a position either above or below the plane of the ring. The resulting possible pair of stereoisomers is called anomers. In an α anomer, the–OH substituent on the anomeric carbon rests on the opposite side (trans) of the ring from the– CH ₂ OH side branch. The alternative form, in which the–CH ₂ OH substituent and the anomeric hydroxyl are on the same side (cis) of the plane of the ring, is called a β anomer. A carbohydrate including two or more joined monosaccharide units is called a disaccharide or polysaccharide (e.g., a trisaccharide), respectively. The two or more monosaccharide units bound together by a covalent bond known as a glycosidic linkage formed via a dehydration reaction, resulting in the loss of a hydrogen atom from one monosaccharide and a hydroxyl group from another. Exemplary disaccharides include sucrose, lactulose, lactose, maltose, isomaltose, trehalose, cellobiose, xylobiose, laminaribiose, gentiobiose, mannobiose, melibiose, nigerose, and rutinose. Exemplary trisaccharides include, but are not limited to, isomaltotriose, nigerotriose, maltotriose, melezitose, maltotriulose, raffinose, and kestose. The term carbohydrate also includes other natural or synthetic stereoisomers of the carbohydrates described herein.

[0074] The term“pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and other animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1–19, incorporated herein by reference.

Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. The salts can be prepared during the final isolation and purification of the compounds or separately by reacting the appropriate compound in the form of the free base with a suitable acid. Representative acid addition salts include acetate, adipate, alginate, L-ascorbate, aspartate, benzoate, benzenesulfonate

(besylate), bisulfate, butyrate, camphorate, camphorsulfonate, citrate, digluconate, formate, fumarate, gentisate, glutarate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate (isethionate), lactate, maleate, malonate, DL-mandelate, mesitylenesulfonate,

methanesulfonate, naphthylenesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylproprionate, phosphonate, picrate, pivalate, propionate, pyroglutamate, succinate, sulfonate, tartrate, L-tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, para-toluenesulfonate (p-tosylate), and undecanoate. Also, basic groups in the compounds disclosed herein can be quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl, diethyl, dibutyl, and diamyl sulfates; decyl, lauryl, myristyl, and steryl chlorides, bromides, and iodides; and benzyl and phenethyl bromides. Examples of acids which can be employed to form therapeutically acceptable salts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid; and organic acids such as oxalic acid, maleic acid, succinic acid, and citric acid.“Basic addition salts” refer to salts derived from appropriate bases, these salts including alkali metal, alkaline earth metal, and quaternary amine salts. Hence, the present invention contemplates sodium, potassium, magnesium, and calcium salts of the compounds disclosed herein, and the like. Basic addition salts can be prepared during the final isolation and purification of the compounds, often by reacting a carboxyl group with a suitable base such as the hydroxide, carbonate, or bicarbonate of a metal cation or with ammonia or an organic primary, secondary, or tertiary amine. The cations of therapeutically acceptable salts include lithium, sodium (by using, e.g., NaOH), potassium (by using, e.g., KOH), calcium (by using, e.g., Ca(OH) ₂ ), magnesium (by using, e.g., Mg(OH) ₂ and magnesium acetate), zinc, (by using, e.g., Zn(OH) ₂ and zinc acetate), and aluminum, as well as nontoxic quaternary amine cations such as ammonium,

tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, tributylamine, pyridine, N,N-dimethylaniline, N- methylpiperidine, N-methylmorpholine, dicyclohexylamine, procaine, dibenzylamine, N,N- dibenzylphenethylamine, 1-ephenamine, and N,N-dibenzylethylenediamine. Other representative organic amines useful for the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine, choline hydroxide, hydroxyethyl morpholine, hydroxyethyl pyrrolidone, imidazole, n-methyl-d-glucamine, N,N'- dibenzylethylenediamine, N,N'-diethylethanolamine, N,N'-dimethylethanolamine, triethanolamine, and tromethamine. Basic amino acids (e.g., 1-glycine and 1-arginine) and amino acids which may be zwitterionic at neutral pH (e.g., betaine (N,N,N-trimethylglycine)) are also contemplated.

[0075] The term“tautomer” refers to a particular isomer of a compound in which a hydrogen and double bond have changed position with respect to the other atoms of the molecule. For a pair of tautomers to exist there must be a mechanism for interconversion. Examples of tautomers include keto-enol forms, imine-enamine forms, amide-imino alcohol forms, amidine-aminidine forms, nitroso-oxime forms, thio ketone-enethiol forms, N-nitroso- hydroxyazo forms, nitro-aci-nitro forms, lactam-lactim forms, ketene-ynol forms, enamine- enamine forms, and pyridione-hydroxypyridine forms.

[0076] The term“polymorphs” refers to a crystalline form of a compound (or a salt, hydrate, or solvate thereof). All polymorphs have the same elemental composition. Different crystalline forms usually have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability, and solubility. Recrystallization solvent, rate of crystallization, storage temperature, and other factors may cause one crystal form to dominate. Various polymorphs of a compound can be prepared by crystallization under different conditions.

[0077] The term“solvate” refers to forms of the compound, or a salt thereof, that are associated with a solvent, usually by a solvolysis reaction. This physical association may include hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. The compounds of the invention may be prepared, e.g., in crystalline form, and may be solvated. Suitable solvates include

pharmaceutically acceptable solvates and further include both stoichiometric solvates and non-stoichiometric solvates. In certain instances, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated in the crystal lattice of a crystalline solid.“Solvate” encompasses both solution-phase and isolable solvates.

Representative solvates include hydrates, ethanolates, and methanolates.

[0078] The term“hydrate” refers to a compound that is associated with water. Typically, the number of the water molecules contained in a hydrate of a compound is in a definite ratio to the number of the compound molecules in the hydrate. Therefore, a hydrate of a compound may be represented, for example, by the general formula R⋅xH ₂ O, wherein R is the compound and wherein x is a number greater than 0. A given compound may form more than one type of hydrates, including, e.g., monohydrates (x is 1), lower hydrates (x is a number greater than 0 and smaller than 1, e.g., hemihydrates (R⋅0.5H ₂ O)), and polyhydrates (x is a number greater than 1, e.g., dihydrates (R⋅2H ₂ O) and hexahydrates (R⋅6H ₂ O)).

[0079] The term“subject” refers to any animal. In certain embodiments, the subject is a mammal. In certain embodiments, the subject is a human (e.g., a man, a woman, or a child). The human may be of either sex and may be at any stage of development. In certain embodiments, the subject has been diagnosed with the condition or disease to be treated. In other embodiments, the subject is at risk of developing the condition or disease. In certain embodiments, the subject is an experimental animal (e.g., mouse, rat, rabbit, dog, pig, or primate). The experimental animal may be genetically engineered. In certain embodiments, the subject is a domesticated animal (e.g., dog, cat, bird, horse, cow, goat, sheep).

[0080] The terms“administer,”“administering,” or“administration” refers to implanting, absorbing, ingesting, injecting, or inhaling an inventive compound, or a pharmaceutical composition thereof.

[0081] The terms“treatment,”“treat,” and“treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a“pathological condition” (e.g., a disease, disorder, or condition, or one or more signs or symptoms thereof) described herein. In some embodiments, treatment may be administered after one or more signs or symptoms have developed or have been observed. In other embodiments, treatment may be administered in the absence of signs or symptoms of the disease or condition. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example, to delay or prevent recurrence.

[0082] The terms“condition,”“disease,” and“disorder” are used interchangeably.

[0083] An“effective amount” of a compound of the present invention or a

pharmaceutical composition thereof refers to an amount sufficient to elicit the desired biological response, i.e., treating the condition. As will be appreciated by those of ordinary skill in this art, the effective amount of a compound of the invention may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the condition being treated, the mode of administration, and the age and health of the subject. In certain embodiments, an effective amount is a therapeutically effective amount. In certain embodiments, an effective amount is a prophylactically effective amount. In certain embodiments, an effective amount is the amount of a compound described herein in a single dose. In certain embodiments, an effective amount is the combined amounts of a compound described herein in multiple doses.

[0084] In certain embodiments, an effective amount is a cleaning-effective amount. The “cleaning-effective” amount of the compound refers to an amount of the compound as described herein which is necessary to remove at least 10% of bacteria from a biofilm as determined by a reduction in numbers of bacteria within the biofilm when compared with a biofilm not exposed to the compound. In certain embodiments, the effective amount is a prophylactically effective amount to prevent normal biofilm formation between normal cleaning times as determined by a statistically significant increase in the number of cells within a biofilm or upon a clean surface. Prevention of normal biofilm formation is determined by the ability to disperse a biofilm using surfactants and or detergents or other chemical treatments which will result in the removal of bacterial cells from a biofilm. To distinguish between normal biofilm formation and treatment with a prophylactically effective amount of the compound as described herein, the treated biofilm must be shown to release 10% or more of its bacteria when compared with a similar biofilm that is not treated when both biofilms are exposed to surfactants and or detergents or other chemical treatments which will result in the removal of bacterial cells from a biofilm.

[0085] A“therapeutically effective amount” of a compound of the present invention or a pharmaceutical composition thereof is an amount sufficient to provide a therapeutic benefit in the treatment of a condition, e.g., iron overload, or to delay or minimize one or more symptoms associated with the condition. A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment of the condition. The term“therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms or causes of the condition, and/or enhances the therapeutic efficacy of another therapeutic agent. In certain embodiments, a therapeutically effective amount is an amount sufficient for chelating a metal described herein. In certain embodiments, a therapeutically effective amount is an amount sufficient for treating a pathological condition described herein. In certain embodiments, a therapeutically effective amount is an amount sufficient for chelating a metal described herein and for treating a pathological condition described herein.

[0086] A“prophylactically effective amount” of a compound of the present invention is an amount sufficient to prevent a condition, e.g., iron overload, or one or more symptoms associated with the condition or prevent its recurrence. A prophylactically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other agents, which provides a prophylactic benefit in the prevention of the condition. The term “prophylactically effective amount” can encompass an amount that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent. In certain embodiments, a prophylactically effective amount is an amount sufficient for chelating a metal described herein. In certain embodiments, a prophylactically effective amount is an amount sufficient for preventing a pathological condition described herein. In certain embodiments, a prophylactically effective amount is an amount sufficient for chelating a metal described herein and for preventing a pathological condition described herein. [0087] The term“biological sample” refers to any sample including tissue samples (such as tissue sections and needle biopsies of a tissue); cell samples (e.g., cytological smears (such as Pap or blood smears) or samples of cells obtained by microdissection); samples of whole organisms (such as samples of yeasts or bacteria); or cell fractions, fragments or organelles (such as obtained by lysing cells and separating the components thereof by centrifugation or otherwise). Other examples of biological samples include blood, serum, urine, semen, fecal matter, cerebrospinal fluid, interstitial fluid, mucous, tears, sweat, pus, biopsied tissue (e.g., obtained by a surgical biopsy or needle biopsy), nipple aspirates, milk, vaginal fluid, saliva, swabs (such as buccal swabs), or any material containing biomolecules that is derived from a first biological sample.

[0088] “Chelation,”“chelating,”“sequestration,” or“sequestering” is the formation or presence of two or more separate coordinate bonds between a polydentate (multiple-bonded) compound and a single central atom. The polydentate compound is typically an organic compound and referred to as a“chelator,”“chelant,”“chelating agent,”“sequestrator,” “sequestering agent,” or“ligand.” The central atom is usually a metal atom or metal ion (e.g., a metal atom or metal ion described herein, such as iron (e.g., Fe(III)), Al(III), chromium (e.g., Cr(VI)), and uranium (e.g., U(VI)), etc.). The chelator may form a stable complex with the central atom through coordinate bonds, inactivating the central atom so that the central atom is less likely to react with other molecules or atoms.

[0089] The term“reactive oxygen species” or“ROS” refers to molecules or ions formed by the incomplete reduction of oxygen. Reactive oxygen species include superoxide anion (O ^•- 2 ), peroxides such as hydrogen peroxide (H ₂ O ₂ ), hydroxyl radical (HO ^• ), and

hypochlorous acid (HClO). These molecules are typically chemically reactive. Reactive oxygen species may be formed by any number of mechanisms (e.g., enzymatically, by ionizing radiation, by reaction oxygen with a metal). In certain embodiments, the reactive oxygen species are formed by the reduction of oxygen by an iron ion, such as Fe ⁺² .

[0090] The term“antimicrobial” refers to a compound having a destructive killing action upon microbes or microorganisms.

[0091] The term“microorganism” refer to very minute, microscopic life forms or organisms, which may be either plant or animal, and which may include, but are not limited to, algae, bacteria, fungi, protozoae, and parasites.

[0092] The term“biofilm formation” refers to the attachment of microorganisms to surfaces and the subsequent development of multiple layers of cells. In certain embodiments, the biofilm is bacterial biofilm. [0093] The term“biocide” refers to a chemical substance or microorganism (e.g., bacteria, fungal cells, protozoa, etc.), which can deter, render harmless, or exert a controlling effect on any harmful organism by chemical or biological means. In some embodiments, the biocides are pesticides such as fungicides, herbicides, insecticides, algicides, molluscicides, miticides and rodenticides. In some embodiments, the biocides are antimicrobials such as germicides, antibiotics, antibacterials, antivirals, antifungals, antiprotozoals and antiparasites.

[0094] The term“fungicide” refers to a compound having either a fungicidal or fungistatic effect upon fungi contacted by the compound. DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS OF THE INVENTION

[0095] Infectious diseases are caused by microbes such as bacteria, fungi, and parasites. These pathogenic micobes typically require one or more metals (e.g., iron, calcium, magnesium, strontium, potassium, sodium, chromium, copper, manganese, molybdenum, zinc, and tungsten) to sustain life. For example, iron is used by cytochromes and as a cofactor for enzymes in electron-transport proteins. Without wishing to be bound by any particular theory, the inventive methods use desferrithiocin analogs, desazadesferrithiocin analogs, and N,N′-di(2-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid monohydrochloride (HBED) analogs as metal chelators in the treatment and/or prevention infectious diseases and the inhibition of biofilm formation.

[0096] In one aspect, the inventive methods for preventing and/or treating an infectious disease comprise administering to a subject in need thereof a compound of any one of Formulae (I-A)-(III-A), or a salt, tautomer, stereoisomer, solvate, hydrate, or a polymorph thereof.

[0097] In certain embodiments, the infectious disease is responsive to the chelation or sequestration of a metal. In certain embodiments, the metal is a monovalent, divalent, tetravalent, pentavalent, or hexavalent metal. In certain embodiments, the metal is a trivalent metal. In certain embodiments, the metal is iron (e.g., Fe(III)). In certain embodiments, the metal is aluminum, thallium, chromium, magnesium, calcium, strontium, nickel, manganese, cobalt, copper, zinc, silver, sodium, potassium, cadmium, mercury, lead, antimony, molybdenum, tungsten, a lanthanide (e.g., cerium), or an actinide (e.g., uranium).

[0098] In certain embodiments, the infectious disease being treated and/or prevented is a bacterial infection. In certain embodiments, the bacterial infection is caused by a Gram- positive bacterium. Exemplary Gram-positive bacteria include, but are not limited to, species of the genera Staphylococcus, Streptococcus, Micrococcus, Peptococcus, Peptostreptococcus, Enterococcus, Bacillus, Clostridium, Lactobacillus, Listeria, Erysipelothrix,

Propionibacterium, Eubacterium, and Corynebacterium. In certain embodiments, the Gram- positive bacterium is a bacterium of the phylum Firmicutes. In certain embodiments, the bacterium is a member of the phylum Firmicutes and the genus Enterococcus, i.e., the bacterial infection is an Enterococcus infection. Exemplary Enterococci bacteria include, but are not limited to, E. avium, E. durans, E. faecalis, E. faecium, E. gallinarum, E. solitarius, E. casseliflavus, and E. raffinosus. In certain embodiments, the Enterococcus infection is an E. faecalis infection. In certain embodiments, the Enterococcus infection is an E. faecium infection. In certain embodiments, the bacteria is a member of the phylum Firmicutes and the genus Staphylococcus, i.e., the bacterial infection is a Staphylococcus infection. Exemplary Staphylococci bacteria include, but are not limited to, S. arlettae, S. aureus, S. auricularis, S. capitis, S. caprae, S. carnous, S. chromogenes, S. cohii, S. condimenti, S. croceolyticus, S. delphini, S. devriesei, S. epidermis, S. equorum, S. felis, S. fluroettii, S. gallinarum, S.

haemolyticus, S. hominis, S. hyicus, S. intermedius, S. kloosii, S. leei, S. lenus, S. lugdunesis, S. lutrae, S. lyticans, S. massiliensis, S. microti, S. muscae, S. nepalensis, S. pasteuri, S.

penttenkoferi, S. piscifermentans, S. psuedointermedius, S. psudolugdensis, S. pulvereri, S. rostri, S. saccharolyticus, S. saprophyticus, S. schleiferi, S. sciuri, S. simiae, S. simulans, S. stepanovicii, S. succinus, S. vitulinus, S. warneri, and S. xylosus. In certain embodiments, the Staphylococcus infection is an S. aureus infection. In certain embodiments, the

Staphylococcus infection is an S. epidermis infection. In certain embodiments, the Gram- positive bacterium is selected from the group consisting of Staphylococcus aureus,

Staphylococcus auricularis, Staphylococcus capitis, Staphylococcus cohnii, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdanensis, Staphylococcus saccharolyticus, Staphylococcus saprophyticus, Staphylococcus schleiferi, Staphylococcus similans, Staphylococcus warneri, Staphylococcus xylosus, Streptococcus agalactiae, Streptococcus anginosus, Streptococcus bovis, Streptococcus canis, Streptococcus equi, Streptococcus milleri, Streptococcus mitior, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus salivarius, Streptococcus sanguis, Bacillus anthracis, Clostridium botulinum, Clostridium perfringens, Clostridium tetani, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus faecium, Erysipelothrix rhusiopathiae, Gardnerella vaginalis, Gemella morbillorum, Mycobacterium abcessus, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium haemophilium, Mycobacterium kansasii, Mycobacterium leprae,

Mycobacterium marinum, Mycobacterium scrofulaceum, Mycobacterium smegmatis, Mycobacterium terrae, Mycobacterium tuberculosis, Mycobacterium ulcerans, and

Peptococcus niger.

[0099] In certain embodiments, the bacterial infection being treated and/or prevented is an infection caused by a Gram-negative bacterium. Exemplary Gram-negative bacteria include, but are not limited to, Escherchia coli, Caulobacter crescentus, Pseudomonas, Agrobacterium tumefaciens, Branhamella catarrhalis, Citrobacter diversus, Enterobacter aerogenes, Klebsiella pneumoniae, Proteus mirabilis, Salmonella typhimurium, Neisseria meningitidis, Serratia marcescens, Shigella sonnei, Neisseria gonorrhoeae, Acinetobacter baumannii, Salmonella enteriditis, Fusobacterium nucleatum, Veillonella parvula,

Bacteroides forsythus, Actinobacillus actinomycetemcomitans, Aggregatibacter

actinomycetemcomitans, Porphyromonas gingivalis, Helicobacter pylori, Francisella tularensis, Yersinia pestis, Morganella morganii, Edwardsiella tarda, and Haemophilus influenzae. In certain embodiments, the Gram-negative bacteria species is Pseudomonas. In certain embodiments, the Gram-negative bacteria species is Pseudomonas aeruginosa.

[00100] In certain embodiments, the bacterial infection being treated and/or prevented is a chronic bacterial infection. As used herein, a“chronic bacterial infection” is a bacterial infection that is of a long duration or frequent recurrence. For example, a chronic middle ear infection, or otitis media, can occur when the Eustachian tube becomes blocked repeatedly due to allergies, multiple infections, ear trauma, or swelling of the adenoids. The definition of “long duration” will depend upon the particular infection. For example, in the case of a chronic middle ear infection, it may last for weeks to months. Exemplary chronic bacterial infections include, but are not limited to, urinary tract infection (most commonly caused by Escherichia coli and/or Staphylococcus saprophyticus), gastritis (most commonly caused by Helicobacter pylori), respiratory infection (such as those commonly afflicting patents with cystic fibrosis, most commonly caused by Pseudomonas aeuroginosa), cystitis (most commonly caused by Escherichia coli), pyelonephritis (most commonly caused by Proteus species, Escherichia coli and/or Pseudomonas sp), osteomyelitis (most commonly caused by Staphylococcus aureus, but also by Escherichia coli), bacteremia, skin infection, rosacea, acne, chronic wound infection, infectious kidney stones (can be caused by Proteus mirabilis), bacterial endocarditis, and sinus infection.

[00101] In certain embodiments, the bacterial infection being treated and/or prevented is caused by an organism resistant to one or more antibiotics. For example, in certain embodiments, the bacterial infection is caused by an organism resistant to penicillin. In certain embodiments, the bacterial infection is caused by an organism resistant to vancomycin (VR). In certain embodiments, the bacterial infection is caused by vancomycin- resistant E. faecalis. In certain embodiments, the bacterial infection is caused by

vancomycin-resistant E. faecium. In certain embodiments, the bacterial infection is caused by vancomycin-resistant Staphylococcus aureus (VRSA). In certain embodiments, the bacterial infection is caused by vancomycin-resistant Enterococci (VRE). In certain embodiments, the bacterial infection is caused by a methicillin-resistant (MR) organism. In certain embodiments, the bacterial infection is caused by methicillin-resistant S. aureus (MRSA). In certain embodiments, the bacterial infection is caused by methicillin-resistant Staphylococcus epidermidis (MRSE). In certain embodiments, the bacterial infection is caused by penicillin-resistant Streptococcus pneumonia. In certain embodiments, the bacterial infection is caused by quinolone-resistant Staphylococcus aureus (QRSA). In certain embodiments, the bacterial infection is caused by multi-drug resistant Mycobacterium tuberculosis.

[00102] In one aspect, the present invention provides methods of inhibiting the formation of biofilms comprising administering to a subject in need thereof a therapeutically effective amount of a compound capable of chelating a metal (e.g., compounds of any one of Fomulae (I-A)-(III-A)). In certain embodiments, the present invention provides methods of inhibiting the formation of biofilms comprising administering to a subject in need thereof a

therapeutically effective amount of a compound capable of chelating a metal and an antimicrobial agent. In certain embodiments, the biofilms are produced by one or more microorganisms selected from the group consisting of bacteria, archaea, protozoa, fungi and algae. In some embodiments, the biofilms are produced by bacteria. In some embodiments, the biofilms are produced by Gram-negative bacteria. In an embodiments, the biofilms are produced by microbial species such as S. epidermidis, E. faecalis, E. coli, P. mirabilis, P. aeruginosa, K. pneumoniae, S. aureus, S. viridans, K. oxytoca, S. saprophyticus, L.

pneumophila, Mycobacterium spp., C. freundii, A. hydrophila, F. nucleatum, A. naeslundii, P. stuartii, S. marcescens, or combinations thereof. In some embodiments, the biofilms are produced by Gram-positive bacteria.

[00103] In some embodiments, the bacterial infection is one or more infections selected from the group consisting of urinary tract infection, gastritis, respiratory infection, cystitis, pyelonephritis, osteomyelitis, bacteremia, skin infection, rosacea, acne, chronic wound infection, infectious kidney stones, bacterial endocarditis, and sinus infection. In certain embodiments, the infectious diseases is pneumonia, urinary tract infection, complicated intra- abdominal infection, or complicated skin/skin structure infection. In certain embodiments, the infectious diseases is nosocomial pneumonia, community-acquired pneumonia, urinary tract infection, complicated intra-abdominal infection, complicated skin/skin structure infection, infectious exacerbations of cystic fibrosis, sepsis, or melioidosis. In certain embodiments, the bacterial infection is respiratory infection. In certain embodiments, the bacterial infection is upper respiratory infection. In certain embodiments, the bacterial infection is pneumonia. In certain embodiments, the bacterial infection is bronchitis.

[00104] In another aspect, provided herein is a method for inhibiting bacterial cell growth comprising contacting bacteria with a compound capable of chelating a metal as described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[00105] In another aspect, provided herein is a method for inducing bacterial

hypersusceptibility comprising contacting a bacterium with a compound capable of chelating a metal as described herein, or a pharmaceutically acceptable salt thereof, or a composition thereof. Hypersusceptibility refers to a condition of abnormal susceptibility to poisons, infective agents, or agents that are entirely innocuous in the normal individual.

[00106] In certain embodiments, the bacterium/a is contacted with the compound in vitro. In certain embodiments, the bacterium/a is contacted with the compound in vivo. In certain embodiments, the bacterium is subsequently contacted with an antibiotic.

[00107] In some embodiments, the compound is administered with one or more additional therapeutically active agents. In certain embodiments, the additional therapeutically active agents are biocides. In certain embodiments, the biocides are antimicrobials. In certain embodiments, the antimicrobials are antibiotics.

[00108] The compounds of Formulae (I-A)-(III-A) can be typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily dosage of the compositions of the present invention will be decided by an attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject or organism will depend upon a variety of factors including the disease, disorder, or condition being treated and the severity of the disorder; the activity of the specific active ingredient employed; the specific composition employed; the age, body weight, general health, sex and diet of the subject; the time of administration, route of administration, and rate of excretion of the specific active ingredient employed; the duration of the treatment; drugs used in combination or coincidental with the specific active ingredient(s) employed; and like factors well known in the medical arts. [00109] The compound or pharmaceutical composition can be administered concurrently with, prior to, or subsequent to, one or more additional therapeutically active agents (e.g., antibiotics, anti-inflammatory agents). In general, each agent will be administered at a dose and/or on a time schedule determined for that agent. In will further be appreciated that the additional therapeutically active agent utilized in this combination can be administered together in a single composition or administered separately in different compositions. The particular combination to employ in a regimen will take into account compatibility of the inventive compound with the additional therapeutically active agent and/or the desired therapeutic effect to be achieved. In general, it is expected that additional therapeutically active agents utilized in combination be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in

combination will be lower than those utilized individually.

[00110] In certain embodiments, the subject administered the chelating agent as provided herein or pharmaceutical composition is a mammal. In certain embodiments, the subject is a human. In certain embodiments, the subject is a patient diagnosed with cystic fibrosis. In certain embodiments, the subject is an immunocompromised subject. In certain embodiments, the subject is a domesticated animal, such as a dog, cat, cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a companion animal such as a dog or cat. In certain embodiments, the subject is a livestock animal such as a cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a zoo animal. In another embodiment, the subject is an experimental animal such as a rodent or non-human primate.

[00111] In another aspect, the present invention provides methods to treat or prevent biofilm formation comprising administering to a subject in need thereof a therapeutically effective amount of a compound capable of chelating a metal or pharmaceutical composition thereof as described herein. In certain embodiments, the provided method treats, cleans, or disinfects a wound by administering the compound or composition as described herein. In certain embodiments, the wounds are chronic wounds, acute wounds, surgical wounds, surgical sites, second and third degree burns, stasis ulcers, tropic lesions, decubitus ulcers, severe cuts, or abrasions.

[00112] In another aspect, the present invention provides methods to treat or prevent biofilm formation comprising contacting an object with an effective amount of a compound capable of chelating a metal or the composition as described herein. In certain embodiments, the provided methods inhibit, reduce, or remove biofilms on an object. In certain

embodiments, the provided method is to inhibit or remove the biofilm on the surface of the object. In certain embodiments, the surface is a hard, rigid surface. In certain embodiments, the surface is selected from the group consisting of a drainpipe, glaze ceramic, porcelain, glass, metal, wood, chrome, plastic, vinyl, and formica. In certain embodiments, the surface is a soft, flexible surface. In certain embodiments, the surface is selected from the group consisting of shower curtains or liners, upholstery, laundry, and carpeting. In certain embodiments, the surface is a food preparation surface, such as kitchen counters, cutting boards, sinks, stoves, refrigerator surfaces, or on sponges. In certain embodiments, the surface is a bathroom surface such as toilets, sinks, bathtubs, showers, and drains. In certain embodiments, the surface is a medical device surface.

[00113] In some embodiment, the contacting of the compound or composition as described herein with the object is carried out by wiping, sponging, or soaking, or laundering means.

[00114] In some embodiments, the provided method is used to prevent or remove biofilm as a dentifrice, a mouthwash, a compound for the treatment of dental caries, acne treatment, cleaning and disinfecting contact lenses, and medically implanted devices that are permanent such as an artificial heart valve or hip joint, and those that are not permanent such as indwelling catheters, pacemakers, surgical pins etc. In some embodiments, the provided method is used to prevent or remove biofilm in situations involving bacterial infection of a host, either human or animal, for example in a topical dressing for burn patients. An example of such a situation would be the infection by P. aeruginosa of superficial wounds such as are found in burn patients or in the lung of a cystic fibrosis patient. In some embodiments, the provided method can be used to control or prevent the development of biofilm in the process of manufacturing integrated circuits, circuit boards or other electronic or microelectronic devices. Metal chelators useful in the present invention

[00115] Compounds provided herein have been found capble of chelating metals, for example, iron. These metal chelators are in useful in treating or preventing diseases and conditions associated microbialn infections that re caused by pathogenic micobes typically requiring one or more metals (e.g., iron, calcium, magnesium, strontium, potassium, sodium, chromium, copper, manganese, molybdenum, zinc, and tungsten) to sustain life. Some of those compounds have been previously described in U.S. Application Publication Noes: US 20100093812, US 20130210870, US 20120184586, US 20120184586, US 20080214630, US 20130030028, US 20140235680, US 2014/0343110, and US 20140323534; and the International Application Publication Noes: WO 2008/115433, WO 2011/028255, WO 2006/107626, WO 2013/090750, and WO 2013/090766, all of which are incorporated by reference herein by entireties. In one aspect of the present invention, the compound used in the inventive methods, compositions, and kits is a compound of Formula (I-A):

and pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, hydrates, or polymorphs thereof, wherein:

R ₁ is hydrogen, optionally substituted alkyl, optionally substituted acyl, an oxygen

protecting group, ;

R ₂ is hydrogen, optionally substituted alkyl, optionally substituted acyl, an oxygen protecting group,–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –R″, or–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –(CH ₂ ) _n – NR ₁₀ –C(=O)O–R″;

each occurrence of R ₃ is independently optionally substituted alkyl, optionally substituted arylalkyl, or–OR ₈ ;

R ₄ , R ₅ , and R ₆ are each independently hydrogen or optionally substituted alkyl; R ₇ is–OR ₉ ,–SR ₉ , or–N(R ^N1 ) ₂ ;

each instance of R ^N1 is independently hydrogen, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -OR ^O1 , or a nitrogen protecting group;

R ^O1 is hydrogen, optionally substituted alkyl, or an oxygen protecting group; R ₈ is hydrogen, optionally substituted alkyl, optionally substituted acyl, an oxygen

protecting group, , ;

R ₉ is hydrogen, optionally substituted alkyl, ,

an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

R ₁₀ is hydrogen, optionally substituted alkyl, optionally substituted acyl, or a nitrogen protecting group;

each instance of R′ is independently hydrogen, optionally substituted C _1-6 alkyl, optionally substituted acyl, or an oxygen protecting group;

R″ is hydrogen, optionally substituted alkyl, optionally substituted acyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group,

, o ;

at least one of R ₁ , R ₈ , R ₉ , and R″ is each occurrence of n is independently an integer from 1 to 8, inclusive; m is an integer from 0 to 1, inclusive;

k is an integer from 0 to 4, inclusive;

x is an integer from 1 to 8, inclusive; and

y is an integer from 0 to 8, inclusive.

[00116] In one aspect of the present invention, the metal chelator used in the inventive methods, compositions, and kits is a compound of Formula (II-A):

or a pharmaceutically acceptable salt thereof;

wherein:

R ₁ is hydrogen, optionally substituted alkyl, optionally substituted acyl, an oxygen

protecting group,

R ₂ is hydrogen, optionally substituted alkyl, optionally substituted acyl, an oxygen protecting group,–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –R″, or–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –(CH ₂ ) _n –NR ₁₀ – C(=O)O–R″;

each occurrence of R ₃ is independently optionally substituted alkyl, optionally substituted arylalkyl, or–OR ₈ ;

R ₄ , R ₅ , and R ₆ are each independently hydrogen or optionally substituted alkyl, ;

R ₇ is–OR ₉ ,–SR ₉ , or–N(R ^N1 ) ₂ ;

each instance of R ^N1 is independently hydrogen, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -OR ^O1 , or a nitrogen protecting group;

R ^O1 is hydrogen, optionally substituted alkyl, or an oxygen protecting group; R ₈ is hydrogen, optionally substituted alkyl, optionally substituted acyl, an oxygen

protecting group, ;

R ₉ is hydrogen, optionally substituted alkyl,

, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

R ₁₀ is hydrogen, optionally substituted alkyl, optionally substituted acyl, or a nitrogen protecting group;

R′ is hydrogen or an oxygen protecting group;

R″ is hydrogen, optionally substituted alkyl, optionally substituted acyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group,

;

each occurrence of n is independently an integer from 1 to 8, inclusive;

k1 is an integer from 0 to 3, inclusive, as valency permits;

m1 is an integer from 0 to 3, inclusive, as valency permits;

x is an integer from 1 to 8, inclusive; and

y is an integer from 0 to 8, inclusive. [00117] In certain embodiments, at least one of R ₁ and R ₉ is or

; or R ₂ is–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –R″ or–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –

(CH ₂ ) _n –NR ₁₀ –C(=O)O–R″, and R″ is ; or R ₃ is

–OR ₈ , R ₈ is and k is 1, 2, 3, or 4.

[00118] In certain embodiments of Formula (I-A) or (II-A), R ₁ is hydrogen, optionally substituted alkyl, optionally substituted acyl, or an oxygen protecting group;

R ₂ is hydrogen, optionally substituted alkyl, optionally substituted acyl, an oxygen protecting group,–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –R″, or–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –(CH ₂ ) _n –NR ₁₀ – C(=O)O–R″;

each occurrence of R ₃ is independently optionally substituted alkyl, optionally substituted arylalkyl, or–OR ₈ ;

R ₄ , R ₅ , and R ₆ are each independently hydrogen or optionally substituted alkyl;

R ₇ is–OR ₉ ,–SR ₉ , or–N(R ^N1 ) ₂ ;

each instance of R ^N1 is independently hydrogen, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -OR ^O1 , or a nitrogen protecting group;

R ^O1 is hydrogen, optionally substituted alkyl, or an oxygen protecting group;

R ₈ is hydrogen, optionally substituted alkyl, acyl, or an oxygen protecting group; R ₉ is hydrogen, optionally substituted alkyl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

R ₁₀ is hydrogen, optionally substituted alkyl, optionally substituted acyl, or a nitrogen protecting group;

R′ is hydrogen or an oxygen protecting group;

R″ is hydrogen, optionally substituted alkyl, optionally substituted acyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

each occurrence of n is independently an integer from 1 to 8, inclusive;

k is an integer from 0 to 4, inclusive;

x is an integer from 1 to 8, inclusive; and

y is an integer from 0 to 8, inclusive.

[00119] In compounds of Formula (I-A) or (II-A), R ₁ is hydrogen, optionally substituted

alkyl, optionally substituted acyl, an oxygen protecting group, , or

. In certain embodiments, R ₁ is hydrogen. In certain embodiments, R ₁ is optionally substituted alkyl. In certain embodiments, R ₁ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₁ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₁ is methyl. In certain embodiments, R ₁ is ethyl. In certain embodiments, R ₁ is propyl. In certain

embodiments, R ₁ is butyl. In certain embodiments, R ₁ is optionally substituted acyl. In certain embodiments, R ₁ is acetyl. In certain embodiments, R ₁ is pivaloyl. In certain embodiments, R ₁ is an oxygen protecting group. In certain embodiments, R ₁ is silyl. In certain

embodiments, R ₁ is TBDPS, TBDMS, TIPS, TES, or TMS. In certain embodiments, R ₁ is MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R ₁ is In certain embodiments, R ₁ is . In certain

embodiments, R ₁ is In certain embodiments, R ₁ is In

certain embodiments, R ₁ is . In certain embodiments, R ₁ is

; wherein all R′ are oxygen protecting groups. In certain embodiments, R ₁

is ; wherein all R′ are oxygen protecting groups. In certain embodiments,

R ₁ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R ₁ is wherein all R' are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R ₁ is

. In certain embodiments, R ₁ is . In certain embodiments, R ₁ is . in certain embodiments, R ₁ is . In certain embodiments, R ₁ is . in certain embodiments, R ₁ is

; wherein all R' are oxygen protecting groups. In certain embodiments, R ₁ is ; wherein all R' are oxygen protecting groups. In certain embodiments, R ₁ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R ₁ is

; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz.

[00120] As used herein, Bn refers to–CH ₂ Ph. As used herein, Bz refers to–C(=O)Ph.

[00121] In compounds of Formula (I-A) or (II-A), R ₂ is hydrogen, optionally substituted alkyl, optionally substituted acyl, an oxygen protecting group,–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y – R″, or–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –(CH ₂ ) _n –NR ₁₀ –C(=O)O–R″. In certain embodiments, R ₂ is hydrogen. In certain embodiments, R ₂ is optionally substituted alkyl. In certain embodiments, R ₂ is C _1-12 alkyl optionally substituted with one or more substituents independently selected from the group consisting of hydroxyl, alkyloxy, and–CO ₂ H. In certain embodiments, R ₂ is– (CH ₂ ) ₂ –OH,–(CH ₂ ) ₃ –OH,–(CH ₂ ) ₄ –OH,–(CH ₂ ) ₅ –OH,–(CH ₂ ) ₆ –OH,–(CH ₂ ) ₇ –OH, or– (CH ₂ ) ₈ –OH. In certain embodiments, R ₂ is–(CH ₂ ) ₂ –OCH ₃ ,–(CH ₂ ) ₃ –OCH ₃ ,–(CH ₂ ) ₄ –OCH ₃ , –(CH ₂ ) ₅ –OCH ₃ ,–(CH ₂ ) ₆ –OCH ₃ ,–(CH ₂ ) ₇ –OCH ₃ , or–(CH ₂ ) ₈ –OCH ₃ . In certain embodiments, R ₂ is–CH ₂ –CO ₂ H,–(CH ₂ ) ₂ –CO ₂ H,–(CH ₂ ) ₃ –CO ₂ H,–(CH ₂ ) ₄ –CO ₂ H, or–(CH ₂ ) ₅ –CO ₂ H. In certain embodiments, R ₂ is C _1-12 alkyl substituted at least with–CO ₂ R ₃₁ , wherein R ₃₁ is substituted or unsubstituted C _1-6 alkyl (e.g.,–CH ₃ ). In certain embodiments, R ₂ is–CH ₂ – CO ₂ R ₃₁ ,–(CH ₂ ) ₂ –CO ₂ R ₃₁ ,–(CH ₂ ) ₃ –CO ₂ R ₃₁ ,–(CH ₂ ) ₄ –CO ₂ R ₃₁ , or–(CH ₂ ) ₅ –CO ₂ R ₃₁ . In certain embodiments, R ₂ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₂ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₂ is methyl. In certain embodiments, R ₂ is ethyl. In certain embodiments, R ₂ is propyl. In certain embodiments, R ₂ is butyl. In certain embodiments, R ₂ is optionally substituted acyl. In certain embodiments, R ₂ is acetyl. In certain embodiments, R ₂ is pivaloyl. In certain embodiments, R ₂ is an oxygen protecting group. In certain embodiments, R ₂ is silyl. In certain embodiments, R ₂ is TBDPS, TBDMS, TIPS, TES, or TMS. In certain embodiments, R ₂ is MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R ₂ is–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –R″. In certain embodiments, R ₂ is . In certain embodiments, R ₂ is . In certain embodiments, R ₂ is . In certain embodiments, R ₂ is . In certain embodiments, R ₂ is . In certain embodiments, R

2 is . In certain embodiments, R ₂ is

. In certain embodiments, R ₂ is

. In certain embodiments, R ₂ is , wherein R is optionally substituted aryl. In certain embodiments, R ₂ is wherein R″ is optionally substituted phenyl. In certain embodiments, R ₂ is , wherein R″ is optionally substituted phenyl. In certain

e , wherein R″ is of the formula:

, wherein R ₁ , R ₃ , k, R ₄ , R ₅ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is , wherein R″ is of the formula: , wherein R ₁ , R ₄ , R ₅ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is , wherein R″ is of the formula:

, wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is , wherein R″ is of the formula:

, wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is , wherein R″ is of the formula:

, wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is , wherein R″ is of the formula: , wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is , wherein R″ is of the formula:

, wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain

embodiments, R ₂ is of the formula: In certain embodiments, R ₂ is , wherein R″ is optionally substituted heteroaryl. In certain embodiments, R ₂ is , wherein R″ is optionally substituted monocyclic heteroaryl. In certain embodiments, R ₂ is , wherein R″ is optionally substituted pyridinyl. In certain embodiments, R ₂ is

, wherein R″ is of the formula:

wherein R ₁ , R ₃ , k, R ₄ , R ₅ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is wherein R" is of the formula:

wherein R ₁ , R ₄ , R ₅ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is wherein R" is of the formula:

wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is wherein R" is of the formula:

wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is wherein R" is of the formula:

wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is wherein R" is of the formula:

wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is , wherein R″ is of the formula: wherein R ₁ , R ₆ , and R ₇ are as defined herein. In certain embodiments, R ₂ is of the formula:

. In certain embodiments, R ₂ is o . In certain embodiments, R ₂ is or

, wherein R ₃₂ is substituted or unsubstituted C _1-6

alkyl (e.g.,–CH ₃ ). In certain embodiments, R ₂ is . In certain embodiments, R

2 is . In certain embodiments, R ₂ is In certain embodiments, R ₂ is In certain embodiments, R ₂ is . In certain embodiments, R ₂ is

; wherein all R′ are oxygen protecting groups. In certain

embodiments, R ₂ is ; wherein all R′ are oxygen protecting groups.

In certain embodiments, R

2 is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain

embodiments, R ₂ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain

embodiments, R ₂ is . In certain embodiments, R ₂ is

In certain embodiments, R ₂ is In certain embodiments, R ₂ is . In certain embodiments, R ₂ is

. In certain embodiments, R ₂ is

wherein all R′ are ox en rotecting groups. In certain embodiments, R ₂ is

wherein all R′ are oxygen protecting groups. In certain

embodiments, R ₂ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain

embodiments, R ₂ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain

embodiments, R ₂ is–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –(CH ₂ ) _n –NR ₁₀ –C(=O)O–R″. In certain embodiments, R ₂ is–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –(CH ₂ ) _n –NH–C(=O)O–R″. In certain

embodiments, R ₂ is . In certain embodiments, R ₂ is . In certain embodiments, R ₂ is

. In certain embodiments, R ₂ is

. In certain embodiments, R ₂ is

. In certain embodiments, R ₂ is In certain embodiments, R ₂ is In certain embodiments, R ₂ is In certain embodiments, R ₂ is . In certain embodiments, R ₂ is

In certain embodiments, R ₂ is

In certain embodiments, R ₂ is

; wherein all R′ are oxygen protecting

groups. In certain embodiments, R ₂ is ; wherein all R′ are oxygen protecting groups. In certain embodiments, R ₂ is

; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain

embodiments, R ₂ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In

certain embodiments, R ₂ is . In certain

embodiments, R ₂ is . In certain

embodiments, R ₂ is In certain

embodiments, R ₂ is In certain embodiments,

R ₂ is In certain embodiments, R ₂ is In certain embodiments, R ₂ is

wherein all R′ are oxygen protecting

groups. In certain embodiments, R ₂ is ; wherein all R′ are oxygen protecting groups. In certain embodiments, R ₂ is

; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain

embodiments, R ₂ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz.

[00122] In compounds of Formula (I-A), R ₁ and all occurrences of R ₂ are hydrogen.

[00123] In compounds of Formula (I-A) or (II-A), each occurrence of R ₃ is independently optionally substituted alkyl, optionally substituted arylalkyl, or–OR ₈ . In certain

embodiments, at least one occurrence of R ₃ is optionally substituted alkyl. In certain embodiments, at least one occurrence of R ₃ is optionally substituted C _1-6 alkyl. In certain embodiments, at least one occurrence of R ₃ is methyl. In certain embodiments, at least one occurrence of R ₃ is ethyl. In certain embodiments, at least one occurrence of R ₃ is propyl. In certain embodiments, at least one occurrence of R ₃ is butyl. In certain embodiments, at least one occurrence of R ₃ is optionally substituted arylalkyl. In certain embodiments, at least one occurrence of R ₃ is benzyl. In certain embodiments, at least one occurrence of R ₃ is–OR ₈ . In certain embodiments, at least one occurrence of R ₃ is–OH. In certain embodiments, at least one occurrence of R ₃ is–O–alkyl. In certain embodiments, at least one occurrence of R ₃ is– O–(C _1-6 alkyl). In certain embodiments, at least one occurrence of R ₃ is–OMe. In certain embodiments, at least one occurrence of R ₃ is–OEt. In certain embodiments, at least one occurrence of R ₃ is–OPr. In certain embodiments, at least one occurrence of R ₃ is–OBu. In certain embodiments, at least one occurrence of R ₃ is–O–acyl. In certain embodiments, at least one occurrence of R ₃ is–O–C(=O)–CH ₃ . In certain embodiments, at least one

occurrence of R ₃ is . In certain embodiments, at least one

occurrence of R ₃ is In certain embodiments, at least one occurrence of

R ₃ is . In certain embodiments, at least one occurrence of R ₃ is

In certain embodiments, at least one occurrence of R ₃ is In certain embodiments, at least one occurrence of R ₃ is

; wherein all R′ are oxygen protecting groups. In certain embodiments,

at least one occurrence of R ₃ is wherein all R′ are oxygen protecting

groups. In certain embodiments, at least one occurrence of R ₃ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, at least one occurrence of R ₃ is

wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, at least one occurrence of R ₃ is . In certain embodiments, at least one occurrence of R ₃ is In certain embodiments, at least one occurrence of R ₃ is

. In certain embodiments, at least one occurrence of R ₃ is

In certain embodiments, at least one occurrence of R ₃ is

In certain embodiments, at least one occurrence of R ₃ is

wherein all R′ are oxygen protecting groups. In certain embodiments, at least one occurrence of R ₃ is ; wherein all R′ are oxygen protecting

groups. In certain embodiments, at least one occurrence of R ₃ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, at least one occurrence of R ₃ is

; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz.

[00124] In compounds of Formula (I-A) or (II-A), R ₄ is hydrogen or optionally substituted alkyl. In certain embodiments, R ₄ is hydrogen. In certain embodiments, R ₄ is optionally substituted alkyl. In certain embodiments, R ₄ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₄ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₄ is methyl. In certain embodiments, R ₄ is ethyl. In certain embodiments, R ₄ is propyl. In certain embodiments, R ₄ is butyl.

[00125] In compounds of Formula (I-A) or (II-A), R ₅ is hydrogen or optionally substituted alkyl. In certain embodiments, R ₅ is hydrogen. In certain embodiments, R ₅ is optionally substituted alkyl. In certain embodiments, R ₅ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₅ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₅ is methyl. In certain embodiments, R ₅ is ethyl. In certain embodiments, R ₅ is propyl. In certain embodiments, R ₅ is butyl.

[00126] In certain embodiments of Formula (I-A) or (II-A), R ₄ and R ₅ are each hydrogen. In certain embodiments, R ₄ and R ₅ are each independently optionally substituted alkyl. In certain embodiments, R ₄ and R ₅ are each independently optionally substituted C _1-6 alkyl. In certain embodiments, R ₄ and R ₅ are each independently unsubstituted C _1-6 alkyl. In certain embodiments, R ₄ and R ₅ are each methyl. In certain embodiments, R ₄ and R ₅ are each ethyl.

[00127] In compounds of Formula (I-A) or (II-A), R ₆ is hydrogen or optionally substituted alkyl. In certain embodiments, R ₆ is hydrogen. In certain embodiments, R ₆ is optionally substituted alkyl. In certain embodiments, R ₆ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₆ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₆ is methyl. In certain embodiments, R ₆ is ethyl. In certain embodiments, R ₆ is propyl. In certain embodiments, R ₆ is butyl.

[00128] In certain embodiments of Formula (I-A) or (II-A), R ₄ and R ₅ are each hydrogen; and R ₆ is optionally substituted alkyl. In certain embodiments, R ₄ and R ₅ are each hydrogen; and R ₆ is optionally substituted C _1-6 alkyl.. In certain embodiments, R ₄ and R ₅ are each hydrogen; and R ₆ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₄ and R ₅ are each hydrogen; and R ₆ is methyl. In certain embodiments, R ₄ and R ₅ are each hydrogen; and R ₆ is ethyl. In certain embodiments, R ₄ and R ₅ are each hydrogen; and R ₆ is propyl. In certain embodiments, R ₄ and R ₅ are each hydrogen; and R ₆ is butyl.

[00129] In certain embodiments of Formula (I-A) or (II-A), R ₄ and R ₅ are each optionally substituted alkyl; and R ₆ is methyl. In certain embodiments, R ₄ and R ₅ are each optionally substituted C _1-6 alkyl; and R ₆ is methyl. In certain embodiments, R ₄ and R ₅ are each methyl; and R ₆ is methyl. In certain embodiments, R ₄ and R ₅ are each ethyl; and R ₆ is methyl.

[00130] In certain embodiments of Formula (I-A) or (II-A), R ₄ and R ₅ are each optionally substituted alkyl; and R ₆ is hydrogen. In certain embodiments, R ₄ and R ₅ are each optionally substituted C _1-6 alkyl; and R ₆ is hydrogen. In certain embodiments, R ₄ and R ₅ are each methyl; and R ₆ is hydrogen. In certain embodiments, R ₄ and R ₅ are each ethyl; and R ₆ is hydrogen. In certain embodiments, R ₄ , R ₅ , and R ₆ are each hydrogen.

[00131] In compounds of Formula (I-A) or (II-A), R ₇ is–OR ₉ ,–SR ₉ , or–N(R ^N1 ) ₂ . In certain embodiments, R ₇ is–N(R ^N1 ) _2, wherein each instance of R ^N1 is independently hydrogen, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -OR ^O1 , or a nitrogen protecting group; and R ^O1 is hydrogen, optionally substituted alkyl, or an oxygen protecting group. In certain embodiments, R ₇ is–N(R ^N1 ) ₂ , wherein each instance of R ^N1 is independently hydrogen, optionally substituted alkyl, -OR ^O1 , or a nitrogen protecting group; and R ^O1 is hydrogen, optionally substituted alkyl, or an oxygen protecting group. In certain embodiments, R ₇ is– N(OR ^O1 )R ^N1 , wherein R ^N1 is hydrogen or optionally substituted alkyl; and R ^O1 is hydrogen or optionally substituted alkyl. In certain embodiments, R ₇ is–N(OH)R ^N1 , wherein R ^N1 is hydrogen or optionally substituted alkyl. In certain embodiments, R ₇ is–N(OH)CH ₃ . In certain embodiments, R ₇ is–OR ₉ . In certain embodiments, R ₇ is–OH. In certain

embodiments, R ₇ is–O–alkyl. In certain embodiments, R ₇ is–O–(C _1-6 alkyl). In certain embodiments, R ₇ is–OMe. In certain embodiments, R ₇ is–OEt. In certain embodiments, R ₇

is–OPr. In certain embodiments, R ₇ is . In certain embodiments, R ₇

is . In certain embodiments, R ₇ is In certain

embodiments, R ₇ is . In certain embodiments, R ₇ is

In certain embodiments, R ₇ is wherein all R′

are oxygen protecting groups. In certain embodiments, R ₇ is wherein all R′ are oxygen protecting groups. In certain embodiments, R ₇ is

wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl,

acetyl, pivaloyl, or Bz. In certain embodiments, R ₇ is wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl,

or Bz. In certain embodiments, R ₇ is . In certain embodiments, R ₇ is

In certain embodiments, R ₇ is In certain

embodiments, R ₇ is . In certain embodiments, R ₇ is

In certain embodiments, R ₇ is ; wherein all R′ are oxygen protecting groups. In certain embodiments, R ₇ is ; wherein

all R′ are oxygen protecting groups. In certain embodiments, R ₇ is

wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl,

acetyl, pivaloyl, or Bz. In certain embodiments, R ₇ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl,

or Bz. In certain embodiments, R ₇ is . In certain embodiments, R ₇ is

In certain embodiments, R ₇ is In certain

embodiments, R ₇ is . In certain embodiments, R ₇ is In certain embodiments, R ₇ is wherein all R′

are oxygen protecting groups. In certain embodiments, R ₇ is ; wherein

all R′ are oxygen protecting groups. In certain embodiments, R ₇ is

wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl,

acetyl, pivaloyl, or Bz. In certain embodiments, R ₇ is wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl,

or Bz. In certain embodiments, R ₇ is . In certain embodiments, R ₇ is

In certain embodiments, R ₇ is In certain embodiments, R ₇ is . In certain embodiments, R ₇ is

. In certain embodiments, R ₇ is ; wherein all R′

are oxygen protecting groups. In certain embodiments, R ₇ is ; wherein

all R′ are oxygen protecting groups. In certain embodiments, R ₇ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl,

acetyl, pivaloyl, or Bz. In certain embodiments, R ₇ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. [00132] In compounds of Formula (I-A) or (II-A), R ₈ is hydrogen, optionally substituted

alkyl, optionally substituted acyl, an oxygen protecting group,

. In certain embodiments, R ₈ is hydrogen. In certain embodiments, R ₈ is optionally substituted alkyl. In certain embodiments, R ₈ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₈ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₈ is methyl. In certain embodiments, R ₈ is ethyl. In certain embodiments, R ₈ is propyl. In certain

embodiments, R ₈ is butyl. In certain embodiments, R ₈ is acyl. In certain embodiments, R ₈ is acetyl. In certain embodiments, R ₈ is pivaloyl. In certain embodiments, R ₈ is an oxygen protecting group. In certain embodiments, R ₈ is silyl. In certain embodiments, R ₈ is TBDPS, TBDMS, TIPS, TES, or TMS. In certain embodiments, R ₈ is MOM, THP, t-Bu, Bn, allyl,

acetyl, pivaloyl, or Bz. In certain embodiments, R ₈ is In certain

embodiments, R ₈ is In certain embodiments, R ₈ is In

certain embodiments, R ₈ is In certain embodiments, R ₈ is In certain embodiments, R ₈ is ; wherein all R′ are

oxygen protecting groups. In certain embodiments, R ₈ is wherein all R′

are oxygen protecting groups. In certain embodiments, R ₈ is wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl,

pivaloyl, or Bz. In certain embodiments, R ₈ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In

certain embodiments, R ₈ is . In certain embodiments, R ₈ is

In certain embodiments, R ₈ is In certain embodiments, R ₈ is In certain embodiments, R ₈ is In

certain embodiments, R ₈ is ; wherein all R′ are oxygen protecting groups.

In certain embodiments, R ₈ is ; wherein all R′ are oxygen protecting

groups. In certain embodiments, R ₈ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain

embodiments, R ₈ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz.

[00133] In compounds of Formula (I-A) or (II-A), R ₉ is hydrogen, optionally substituted

alkyl, , an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom. In certain embodiments, R ₉ is hydrogen. In certain embodiments, R ₉ is optionally substituted alkyl. In certain embodiments, R ₉ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₉ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₉ is methyl. In certain embodiments, R ₉ is ethyl. In certain embodiments, R ₉ is propyl. In certain embodiments, R ₉ is butyl. In certain

embodiments, R ₉ is In certain embodiments, R ₉ is

In certain embodiments, R ₉ is . In certain embodiments, R ₉ is

. In certain embodiments, R ₉ is In certain

embodiments, R ₉ is ; wherein all R′ are oxygen protecting groups. In

certain embodiments, R ₉ is ; wherein all R′ are oxygen protecting groups. In certain embodiments, R ₉ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain

embodiments, R ₉ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R ₉

is In certain embodiments, R ₉ is . In certain

embodiments, R ₉ is In certain embodiments, R ₉ is In

certain embodiments, R ₉ is . In certain embodiments, R ₉ is

; wherein all R′ are oxygen protecting groups. In certain embodiments, R ₉ is ; wherein all R′ are oxygen protecting groups. In certain embodiments,

R ₉ is wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R ₉ is

; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R ₉ is an oxygen protecting group when attached to an oxygen atom. In certain embodiments, when attached to an oxygen atom, R ₉ is silyl. In certain embodiments, when attached to an oxygen atom, R ₉ is TBDPS, TBDMS, TIPS, TES, or TMS. In certain embodiments, when attached to an oxygen atom, R ₉ is MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R ₉ is a sulfur protecting group when attached to a sulfur atom. In certain embodiments, when attached to a sulfur atom, R ₉ is acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2- pyridine-sulfenyl, or triphenylmethyl.

[00134] In compounds of Formula (I-A) or (II-A), R ₁₀ is hydrogen, optionally substituted alkyl, optionally substituted acyl, or a nitrogen protecting group. In certain embodiments, R ₁₀ is hydrogen. In certain embodiments, R ₁₀ is optionally substituted alkyl. In certain

embodiments, R ₁₀ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₁₀ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₁₀ is methyl. In certain embodiments, R ₁₀ is ethyl. In certain embodiments, R ₁₀ is propyl. In certain embodiments, R ₁₀ is butyl. In certain embodiments, R ₁₀ is optionally substituted acyl. In certain embodiments, R ₁₀ is acetyl. In certain embodiments, R ₁₀ is pivaloyl. In certain embodiments, R ₁₀ is a nitrogen protecting group. In certain embodiments, R ₁₀ is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, or Ts.

[00135] As generally defined herein, each instance of R' is independently hydrogen, optionally substituted C _1-6 alkyl, optionally substituted acyl, or an oxygen protecting group. In certain embodiments, R' is optionally substituted C _1-6 alkyl, optionally substituted acyl, or an oxygen protecting group. In certain embodiments, all R' are hydrogen. In certain embodiments, all R' are oxygen protecting group. In certain embodiments, R' is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz.

[00136] In compounds of Formula (I-A) or (II-A), at least one R′ is hydrogen or an oxygen protecting group. In certain embodiments, at least one R′ is hydrogen. In certain embodiments, at least one R′ is an oxygen protecting group. In certain embodiments, at least one R′ is silyl. In certain embodiments, at least one R′ is TBDPS. In certain embodiments, at least one R′ is TBDMS. In certain embodiments, at least one R′ is TIPS. In certain

embodiments, at least one R′ is TES. In certain embodiments, at least one R′ is TMS. In certain embodiments, at least one R′ is MOM. In certain embodiments, at least one R′ is THP. In certain embodiments, at least one R′ is t-Bu. In certain embodiments, at least one R′ is Bn. In certain embodiments, at least one R′ is allyl. In certain embodiments, at least one R′ is acetyl. In certain embodiments, at least one R′ is pivaloyl. In certain embodiments, at least one R′ is Bz. In certain embodiments, all R′ are hydrogen. In certain embodiments, all R′ are oxygen protecting groups. In certain embodiments, all R′ are silyl. In certain embodiments, all R′ are TBDPS. In certain embodiments, all R′ are TBDMS. In certain embodiments, all R′ are TIPS. In certain embodiments, all R′ are TES. In certain embodiments, all R′ are TMS. In certain embodiments, all R′ are MOM. In certain embodiments, all R′ are THP. In certain embodiments, all R′ are t-Bu. In certain embodiments, all R′ are Bn. In certain embodiments, all R′ are allyl. In certain embodiments, all R′ are acetyl. In certain embodiments, all R′ are pivaloyl. In certain embodiments, all R′ are Bz.

[00137] In compounds of Formula (I-A) or (II-A), R″ is hydrogen, optionally substituted

alkyl, optionally substituted acyl, an oxygen protecting group, or . In certain embodiments, R″ is hydrogen. In certain embodiments, R″ is optionally substituted alkyl. In certain embodiments, R″ is optionally substituted C _1-6 alkyl. In certain embodiments, R″ is unsubstituted C _1-6 alkyl. In certain embodiments, R″ is methyl. In certain embodiments, R″ is substituted methyl. In certain embodiments, R″ is–CH ₂ –CO ₂ H. In certain embodiments, R″ is–CH ₂ –CO ₂ (substituted or unsubstituted C _1-6 alkyl) (e.g.,–CH ₂ – CO ₂ Me). In certain embodiments, R″ is ethyl. In certain embodiments, R″ is propyl. In certain embodiments, R″ is butyl. In certain embodiments, R″ is acyl. In certain

embodiments, R″ is acetyl. In certain embodiments, R″ is pivaloyl. In certain embodiments, R″ is an oxygen protecting group. In certain embodiments, R″ is silyl. In certain

embodiments, R″ is TBDPS, TBDMS, TIPS, TES, or TMS. In certain embodiments, R″ is MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R″ is

In certain embodiments, R″ is In certain

embodiments, R″ is In certain embodiments, R″ is In

certain embodiments, R″ is In certain embodiments, R″ is ; wherein all R′ are oxygen protecting groups. In certain embodiments, R″

is ; wherein all R′ are oxygen protecting groups. In certain embodiments,

R″ is ; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R″ is

; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R″ is

In certain embodiments, R″ is . In certain

embodiments, R″ is In certain embodiments, R″ is In certain embodiments, R″ is In certain embodiments, R″ is

; wherein all R′ are oxygen protecting groups. In certain embodiments, R″

is ; wherein all R′ are oxygen protecting groups. In certain embodiments,

R″ is wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz. In certain embodiments, R″ is

; wherein all R′ are silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or Bz.

[00138] In compounds of Formula (I-A), at least one of R ₁ , R ₈ , R ₉ , and R″ is

. In certain embodiments, at least one of R ₁ , R ₈ , R ₉ , and R″ is , , , or . In certain embodiments, at least two of R ₁ , R ₈ , R ₉ , and R″ are

. In certain embodiments, at least two of R ₁ , R ₈ ,

R ₉ , and R″ are , , , or

. In certain embodiments, at least three of R ₁ , R ₈ , R ₉ , and R″ are . In certain embodiments, at least three of R ₁ , R ₈ , R ₉ , and R″ are , , , or

. In certain embodiments, R ₁ , R ₈ , R ₉ , and R″ are each

In certain embodiments, R ₁ , R ₈ , R ₉ , and R″ are

each

[00139] In compounds of Formula (I-A) or (II-A), each occurrence of n is independently an integer from 1 to 8, inclusive. In certain embodiments, at least one occurrence of n is 1. In certain embodiments, at least one occurrence of n is 2. In certain embodiments, at least one occurrence of n is 3. In certain embodiments, at least one occurrence of n is 4. In certain embodiments, at least one occurrence of n is 5. In certain embodiments, at least one occurrence of n is 6. In certain embodiments, at least one occurrence of n is 7. In certain embodiments, at least one occurrence of n is 8.

[00140] In compounds of Formula (I-A), m is an integer from 0 to 1, inclusive. In certain embodiments, m is 0. In certain embodiments, m is 1.

[00141] In compounds of Formula (I-A), k is an integer from 0 to 4, inclusive. In certain embodiments, k is 0. In certain embodiments, k is 1. In certain embodiments, k is 2. In certain embodiments, k is 3. In certain embodiments, k is 4. [00142] In compounds of Formula (II-A), k1 is an integer from 0 to 3, inclusive. In certain embodiments, k1 is 0. In certain embodiments, k1 is 1. In certain embodiments, k1 is 2. In certain embodiments, k1 is 3.

[00143] In compounds of Formula (I-A) or (II-A), x is an integer from 1 to 8, inclusive. In certain embodiments, x is 1. In certain embodiments, x is 2. In certain embodiments, x is 3. In certain embodiments, x is 4. In certain embodiments, x is 5. In certain embodiments, x is 6. In certain embodiments, x is 7. In certain embodiments, x is 8.

[00144] In compounds of Formula (I-A) or (II-A), y is an integer from 0 to 8, inclusive. In certain embodiments, y is 0. In certain embodiments, y is 1. In certain embodiments, y is 2. In certain embodiments, y is 3. In certain embodiments, y is 4. In certain embodiments, y is 5. In certain embodiments, y is 6. In certain embodiments, y is 7. In certain embodiments, y is 8.

[00145] In compounds of Formula (I-A) or (II-A), all combinations of n, x, and y are contemplated. In certain embodiments, n is 2; x is 0; and y is 1. In certain embodiments, n is 2; x is 0; and y is 2. In certain embodiments, n is 2; x is 0; and y is 3. In certain embodiments, n is 2; x is 0; and y is 4.

[00146] The compound of Formula (I-A) may have one or more chiral centers. In certain embodiments, the compound of Formula (I-A) is of Formula (I-B):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00147] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00148] When m is 1, the group–OR ₂ of Formula (I-A) may be at any position, as valency permits, of the phenyl ring of Formula (I-A). In certain embodiments, m is 1,–OR ₂ of Formula (I-A) is at the 3′-position of the phenyl ring of Formula (I-A), and thus the compound of Formula (I-A) is of Formula (I-C):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00149] In certain embodiments, the compound of Formula (I-A) is of the formula:

, , or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00150] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00151] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00152] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00153] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00154] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00155] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00156] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00157] In certain embodiments the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00158] In certain embodiments, m is 1, -OR ₂ of Formula (I-A) is at the 4'-position of the phenyl ring of Formula ( -A), and the compound of Formula (I-A) is of Formula (I-D):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00159 In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceu tic ally acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00160] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00161] In certain embodiments, the compound of Formula (I-A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00162] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00163] In certain embodiments, the compound of Formula (I-A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00164] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00165] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00166] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00167] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[0016 In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[0016 In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00170] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

,

, , , , or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00171] In certain embodiments, the compound of Formula (I-A) is of the formula:

, , or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00172] In certain embodiments, the compound of Formula (I-A) is of the formula:

, , or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00173] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00174] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00175] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00176] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00177] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00178] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00179] In certain embodiments, the compound of Formula (I-A) is of Formula (E-1) or (E-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00180] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00181] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00182] In certain embodiments, the compound of Formula (I-A) is of Formula (I-E-3) or (I-E-4):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00183] In certain embodiments, the compound of Formula (A) is of the formula:

,

,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00184] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00185] In certain embodiments, the compound of Formula (I-A) is of Formula (I-X-1):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00186] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00187] In certain embodiments the com ound of Formula I-A is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00188] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00189] In certain embodiments, the compound of Formula (I-A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00190] In certain embodiments, the compound of Formula (I-A) is of Formula (I-F-1) or (I-F-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00191 In certain embodiments the com ound of Formula I-A is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00192] In certain embodiments, the compound of Formula (I-A) is of the formula:

, , , ,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00193] In certain embodiments, the compound of Formula (I-A) is of Formula (I-F-3) or (I-F-4 :

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00194] In certain embodiments, the compound of Formula (I-A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00195] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

,

, , or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00196] In certain embodiments, the compound of Formula (I-A) is of Formula (I-G-1) or (I-G-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00197] In certain embodiments, the compound of Formula (I-A) is of the formula:

, , or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00198] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00199] In certain embodiments, the compound of Formula (I-A) is of Formula (I-H-1) or (I-H-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00200] In certain embodiments, the compound of Formula (I-A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00201] In certain embodiments, the compound of Formula (I-A) is of Formula (I-I-1) or (I-I-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00202] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00203] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00204] In certain embodiments, the compound of Formula (I-A) is of Formula (I-J-1) or (I- -2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00205] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00206] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00207] In certain embodiments, the compound of Formula (I-A) is of Formula (I-K-1) or (I-K-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00208] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00209] In certain embodiments, the compound of Formula (I-A) is of the formula:

, ,

,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00210] In certain embodiments, the compound of Formula (I-A) is of Formula (I-L-1) or (I-L-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00211] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00212] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

,

,

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00213] In certain embodiments, the compound of Formula (I-A) is of Formula (I-M-1) or (I-M-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

00214 In certain embodiments the com ound of Formula I-A is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00215] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

, ,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00216] In certain embodiments, the compound of Formula (I-A) is of Formula (I-N-1) or (I-N-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00217] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

, ,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00218] In certain embodiments, the compound of Formula (I-A) is of the formula:

, ,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00219] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00220] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

,

,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00221] In certain embodiments, the compound of Formula (I-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00222] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00223] In certain embodiments, the compound of Formula (I-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00224] In certain embodiments, the compounds of Formula (II-A) is of Formula (II-A-x):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00225] In certain embodiments, the compounds of Formula (II-A) is of one of the following formula

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00226] In certain embodiments, the compounds of Formula (II-A) is of one of the following formula

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00227] In certain embodiments, the compounds of Formula (II-A) is of one of the following formulae:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00228] In certain embodiments, the compounds of Formula (II- A) is of one of the following formula

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00229] In certain embodiments, the compounds of Formula (II- A) is of one of the following formula

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00230] In certain embodiments, the compounds of Formula (II-A) is of the following formula:

[00231] In certain embodiments, the compounds of Formula (II-A) is of one of the following formulae:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00232] In certain embodiments, the compounds of Formula (II-A) is of one of the following formulae:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00233] In certain embodiments, the compounds of Formula (II-A) is of one of the following formulae:

,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00234] In certain embodiments, the compounds of Formula (II-A) is of one of the following formulae:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00235] In certain embodiments the com ounds of Formula II-A) is of Formula (II-A-a):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00236] The group–OR ₂ of Formula (II-A-a) may be at any position, as valency permits, of the pyridyl ring of Formula (II-A-a). In certain embodiments,–OR ₂ of Formula (II-A-a) is at the 3′-position of the pyridyl ring of Formula (II-A-a), and the compound of Formula (II- A-a) is of Formula (II-C):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00237] In certain embodiments,–OR ² of Formula (II-A-a) is at the 4′-position of the pyridyl ring of Formula (II-A-a), and the compound of Formula (II-A-a) is of Formula (II- D):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00238] In certain embodiments, the compound of Formula (II-A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00239] In certain embodiments, the compound of Formula (II-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00240] In certain embodiments, the compound of Formula (II-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00241] In certain embodiments, the compound of Formula (II-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00242] In certain embodiments, the compound of Formula (II-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00243 In certain embodiments the com ound of Formula II-A is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00244] In certain embodiments, the compound of Formula (II-A) is of Formula (II-E):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00245] In certain embodiments, the compound of Formula (II-A) is of Formula (II-F):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00246] In certain embodiments, the compound of Formula (II-A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00247] In certain embodiments, the compound of Formula (II-A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00248] In certain embodiments, the compound of Formula (II-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00249] In certain embodiments, the compound of Formula (II-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00250] In certain embodiments, the compound of Formula (II-A) is of Formula (II-G):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00251] In certain embodiments, the compound of Formula (II-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00252] In certain embodiments, the compound of Formula (II-A) is of Formula (II-H):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00253] In certain embodiments, the compound of Formula (II-A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00254] In certain embodiments, the compound of Formula (A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00255] In certain embodiments the com ound of Formula A is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00256] In certain embodiments, the compound of Formula (A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof, wherein R ₃₀ is H, substituted or unsubstituted C _1-6 alkyl (e.g.,–CH ₃ ), or an oxygen protecting group; and a is 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 4, 5, 6, 7, or 8).

[00257] In certain embodiments, the compound of Formula (A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00258] In certain embodiments, the compound of Formula (A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00259] In certain embodiments, the compound of Formula (A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof, wherein b is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g. , 1, 2, 3, 4, or 5).

[00260] In certain embodiments, the compound of Formula (A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00261] In certain embodiments, the compound of Formula (A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00262] In certain embodiments, the compound of Formula (A) is of the formula:

,

,

,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00263 In certain embodiments the com ound of Formula A is of the formula:

,

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00264] In certain embodiments, the compound of Formula (A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00265] In certain embodiments, the compound of Formula (A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00266] In certain embodiments, the compound of Formula (A) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00267] In certain embodiments, the compound of Formula (A) is of the formula:

, ,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00268] In certain embodiments, the compound of Formula (A) is of the formula:

,

,

, ,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00269] In certain embodiments, the compound of Formula (A) is not of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00270] In certain embodiments, when R ₇ is–OH, R ₂ is not H or–(CH ₂ CH ₂ O) ₂ CH ₃ . In certain embodiments, when R ₇ is–OH, R ₂ is not H or–[(CH ₂ ) _n –O] _x –[(CH ₂ ) _n –O] _y –R″. In certain embodiments, when R ₇ is–OH,–OR ₂ is attached to the 5′-position of the pyridinyl ring. [00271] In certain embodiments, the compounds useful in the inventive methods are of Formula (II-J):

wherein:

represents a single bond or double bond;

W ₁ -W ₃ are independently CR ₂₂ , CHR ₂₂ , NR ₂₃ , oxygen, or sulfur, provided that: when W ₃ is nitrogen, R ₂₃ is null, and

when R ₂₁ is methyl or hydrogen, W ₁ is not sulfur;

W ₄ is CHR ₂₂ , CR ₂₂ , or NR ₂₃ , as valency permits;

Z is–OR ₁₁ ,–NR ₁₂ R ₁₃ , morpholine, or optionally substituted piperazinyl;

R ₁₁ is–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ ,–[(CH ₂ ) _p –NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ , or– [(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ ;

R ₁₂ is hydrogen, optionally substituted alkyl,–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ ,– [(CH ₂ ) _p – NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ , or–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ ;

R ₁₃ is hydrogen or optionally substituted alkyl;

p and q are independently an integer from 1 to 8, inclusive;

u is an integer from 0 to 8, inclusive;

v is an integer from 1 to 8, inclusive;

R ₁₄ and R ₁₅ are independently hydrogen, optionally substituted alkyl, or optionally substituted acyl;

R ₁₆ is hydrogen, optionally substituted alkyl, or optionally substituted alkoxyl; R ₁₇ is–OR ₁₈ or–N(R ^N1 ) ₂ ;

each instance of R ^N1 is independently hydrogen, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -OR ^O1 , or a nitrogen protecting group;

R ^O1 is hydrogen, optionally substituted alkyl, or an oxygen protecting group; R ₁₈ is hydrogen, optionally substituted alkyl, or optionally substituted arylalkyl; R ₁₉ is optionally substituted alkyl or–(CH ₂ ) _s –N(OH)C(=O)R ₂₀ ;

s is an integer from 1 to 8, inclusive;

R ₂₀ is optionally substituted alkyl; R ₂₁ is hydrogen or optionally substituted alkyl;

each occurrence of R ₂₂ is independently null, hydrogen, or optionally substituted alkyl; and

each occurrence of R ₂₃ is independently null, hydrogen, or optionally substituted alkyl; or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00272] In certain embodiments, the compounds useful in the inventive methods are of Formula (II-J), and pharmaceutically acceptable salts thereof, wherein:

represents a single bond or double bond;

each one of W ₁ , W ₂ , and W ₃ is independently CR ₂₂ , CHR ₂₂ , NR ₂₃ , oxygen, or sulfur, provided that:

when W ₃ is nitrogen, R ₂₃ is null, and

when R ₂₁ is methyl or hydrogen, W ₁ is not sulfur;

W ₄ is CHR ₂₂ , CR ₂₂ , or NR ₂₃ , as valency permits;

Z is–OR ₁₁ ,–NR ₁₂ R ₁₃ , morpholine, or optionally substituted piperazinyl;

R ₁₁ is–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ ,–[(CH ₂ ) _p –NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ , or–

[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ ;

R ₁₂ is hydrogen, optionally substituted alkyl,–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ ,–

[(CH ₂ ) _p – NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ , or–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ ;

R ₁₃ is hydrogen or optionally substituted alkyl;

p and q are independently an integer from 1 to 8, inclusive;

u is an integer from 0 to 8, inclusive;

v is an integer from 1 to 8, inclusive;

R ₁₄ and R ₁₅ are independently hydrogen, optionally substituted alkyl, or optionally substituted acyl;

R ₁₆ is hydrogen, optionally substituted alkyl, or optionally substituted alkoxyl;

R ₁₇ is–OR ₁₈ or–N(R ^N1 ) ₂ ;

each instance of is R ^N1 is independently hydrogen, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -OR ^O1 , or a nitrogen protecting group;

R ^O1 is hydrogen, optionally substituted alkyl, or an oxygen protecting group;

R ₁₈ is hydrogen, optionally substituted alkyl, or optionally substituted arylalkyl;

R ₂₁ is hydrogen or optionally substituted alkyl; each occurrence of R ₂₂ is independently null, hydrogen, or optionally substituted alkyl; and

each occurrence of R ₂₃ is independently null, hydrogen, or optionally substituted alkyl.

[00273] In certain embodiments of Formula (II-J), the compounds useful in the inventive methods are of one of the following formulae:

[00274] In certain embodiments, the compounds useful in the inventive methods are of Formula (II-J′):

wherein:

represents a single bond or double bond;

W ₁ -W ₃ are independently CR ₂₂ , CHR ₂₂ , NR ₂₃ , oxygen, or sulfur, provided that:

when W ₃ is nitrogen, R ₂₃ is null, and

when R ₂₁ is methyl or hydrogen, W ₁ is not sulfur;

W ₄ is CHR ₂₂ , CR ₂₂ , or NR ₂₃ , as valency permits;

Z is–OR ₁₁ ,–NR ₁₂ R ₁₃ , morpholine, or optionally substituted piperazinyl;

R ₁₁ is–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ ,–[(CH ₂ ) _p –NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ , or–

[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ ;

R ₁₂ is hydrogen, optionally substituted alkyl,–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ ,–

[(CH ₂ ) _p – NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ , or–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ ; R ₁₃ is hydrogen or optionally substituted alkyl;

p and q are independently an integer from 1 to 8, inclusive;

u is an integer from 0 to 8, inclusive;

v is an integer from 1 to 8, inclusive;

R ₁₄ and R ₁₅ are independently hydrogen, optionally substituted alkyl, or optionally substituted acyl;

R ₁₆ is hydrogen, optionally substituted alkyl, or optionally substituted alkoxyl;

R ₁₇ is–OR ₁₈ or–N(R ^N1 ) ₂ ;

each instance of is R ^N1 is independently hydrogen, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heteroaryl, -OR ^O1 , or a nitrogen protecting group;

R ^O1 is hydrogen, optionally substituted alkyl, or an oxygen protecting group;

R ₁₈ is hydrogen, optionally substituted alkyl, or optionally substituted arylalkyl;

R ₁₉ is optionally substituted alkyl or–(CH ₂ ) _s –N(OH)C(=O)R ₂₀ ;

s is an integer from 1 to 8, inclusive;

R ₂₀ is optionally substituted alkyl;

R ₂₁ is hydrogen or optionally substituted alkyl;

each occurrence of R ₂₂ is independently null, hydrogen, or optionally substituted alkyl; and

each occurrence of R ₂₃ is independently null, hydrogen, or optionally substituted alkyl; or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00275] In certain embodiments of Formula (II-J′), the compounds useful in the inventive methods are of one of the following formulae:

, .

[00276] In compounds of Formula (II-J) or (II-J′), Z is–OR ₁₁ ,–NR ₁₂ R ₁₃ , optionally substituted heteroaryl, or optionally substituted heterocyclyl. In certain embodimetns, Z is– OR ₁₁ ,–NR ₁₂ R ₁₃ , morpholine, or optionally substituted piperazinyl. In compounds of Formula (II-J), Z is–OR ₁₁ ,–NR ₁₂ R ₁₃ , morpholine, or optionally substituted piperazinyl. In certain embodiments, Z is–OR ₁₁ . In certain embodiments, Z is–O–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ . In certain embodiments, Z is In certain embodiments, Z is In certain embodiments, Z is In certain embodiments, Z is In certain embodiments, Z is . In certain embodiments, Z is In certain embodiments, Z is . In certain embodiments, Z is–O–[(CH ₂ ) _p – NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ . In certain embodiments, Z is–O–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v – R ₁₅ . In certain embodiments, Z is–NR ₁₂ R ₁₃ . In certain embodiments, Z is morpholine. In certain embodiments, Z is unsubstituted piperazinyl. In certain embodiments, Z is substituted piperazinyl. In certain embodiments, Z is piperazinyl substituted at the 4-position with an optionally substituted alkyl. In certain embodiments, Z is 4-(2-hydroxyethyl)-piperazin-1-yl.

[00277] In compounds of Formula (II-J) or (II-J′), R ₁₁ is–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ , –[(CH ₂ ) _p –NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ , or–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ . In certain embodiments, R ₁₁ is–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ . In certain embodiments, R ₁₁ is In certain embodiments, R ₁₁ is In certain embodiments, R ₁₁ is . In certain embodiments, R ₁₁ is . In certain embodiments, R ₁₁ is . In certain embodiments, R ₁₁ is In certain embodiments, R ₁₁ is In certain embodiments, R ₁₁ is–[(CH ₂ ) _p – NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ . In certain embodiments, R ₁₁ is–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v – R ₁₅ .

[00278] In compounds of Formula (II-J) or (II-J′), R ₁₂ is hydrogen, optionally substituted alkyl,–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ ,–[(CH ₂ ) _p – NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ , or–[(CH ₂ ) _p – O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ . In certain embodiments, R ₁₂ is hydrogen. In certain embodiments, R ₁₂ is optionally substituted alkyl. In certain embodiments, R ₁₂ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₁₂ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₁₂ is methyl. In certain embodiments, R ₁₂ is ethyl. In certain embodiments, R ₁₂ is propyl. In certain embodiments, R ₁₂ is butyl. In certain embodiments, R ₁₂ is–[(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –O] _v –R ₁₄ . In certain embodiments, R ₁₂ is In certain embodiments, R ₁₂ is . In certain embodiments, R ₁₂ is In certain embodiments, R ₁₂ is . In certain embodiments, R ₁₂ is . In certain embodiments, R ₁₂ is In certain embodiments, R ₁₂ is In certain embodiments, R ₁₂ is–[(CH ₂ ) _p – NH] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ . In certain embodiments, R ₁₂ is– [(CH ₂ ) _p –O] _u –[(CH ₂ ) _q –NR ₁₄ ] _v –R ₁₅ .

[00279] In compounds of Formula (II-J) or (II-J′), R ₁₃ is hydrogen or optionally substituted alkyl. In certain embodiments, R ₁₃ is hydrogen. In certain embodiments, R ₁₃ is optionally substituted alkyl. In certain embodiments, R ₁₃ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₁₃ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₁₃ is methyl. In certain embodiments, R ₁₃ is ethyl. In certain embodiments, R ₁₃ is propyl. In certain embodiments, R ₁₃ is butyl.

[00280] In compounds of Formula (II-J) or (II-J′), p is an integer from 1 to 8, inclusive. In certain embodiments, p is 1. In certain embodiments, p is 2. In certain embodiments, p is 3. In certain embodiments, p is 4. In certain embodiments, p is 5. In certain embodiments, p is 6. In certain embodiments, p is 7. In certain embodiments, p is 8.

[00281] In compounds of Formula (II-J) or (II-J′), q is an integer from 1 to 8, inclusive. In certain embodiments, q is 1. In certain embodiments, q is 2. In certain embodiments, q is 3. In certain embodiments, q is 4. In certain embodiments, q is 5. In certain embodiments, q is 6. In certain embodiments, q is 7. In certain embodiments, q is 8.

[00282] In compounds of Formula (II-J) or (II-J′), u is an integer from 0 to 8, inclusive. In certain embodiments, u is 0. In certain embodiments, u is 1. In certain embodiments, u is 2. In certain embodiments, u is 3. In certain embodiments, u is 4. In certain embodiments, u is 5. In certain embodiments, u is 6. In certain embodiments, u is 7. In certain embodiments, u is 8.

[00283] In compounds of Formula (II-J) or (II-J′), v is an integer from 1 to 8, inclusive. In certain embodiments, v is 1. In certain embodiments, v is 2. In certain embodiments, v is 3. In certain embodiments, v is 4. In certain embodiments, v is 5. In certain embodiments, v is 6. In certain embodiments, v is 7. In certain embodiments, v is 8.

[00284] In compounds of Formula (II-J) or (II-J′), R ₁₄ is hydrogen, optionally substituted alkyl, or optionally substituted acyl. In certain embodiments, R ₁₄ is hydrogen. In certain embodiments, R ₁₄ is optionally substituted alkyl. In certain embodiments, R ₁₄ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₁₄ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₁₄ is methyl. In certain embodiments, R ₁₄ is ethyl. In certain embodiments, R ₁₄ is propyl. In certain embodiments, R ₁₄ is butyl. In certain embodiments, R ₁₄ is acyl. In certain embodiments, R ₁₄ is acetyl.

[00285] In compounds of Formula (II-J) or (II-J′), R ₁₅ is hydrogen, optionally substituted alkyl, or optionally substituted acyl. In certain embodiments, R ₁₅ is hydrogen. In certain embodiments, R ₁₅ is optionally substituted alkyl. In certain embodiments, R ₁₅ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₁₅ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₁₅ is methyl. In certain embodiments, R ₁₅ is ethyl. In certain embodiments, R ₁₅ is propyl. In certain embodiments, R ₁₅ is butyl. In certain embodiments, R ₁₅ is optionally substituted acyl. In certain embodiments, R ₁₅ is acetyl. [00286] In compounds of Formula (II-J) or (II-J′), R ₁₆ is hydrogen, optionally substituted alkyl, or optionally substituted alkoxyl. In certain embodiments, R ₁₆ is hydrogen. In certain embodiments, R ₁₆ is optionally substituted alkyl. In certain embodiments, R ₁₆ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₁₆ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₁₆ is methyl. In certain embodiments, R ₁₆ is ethyl. In certain embodiments, R ₁₆ is propyl. In certain embodiments, R ₁₆ is butyl. In certain embodiments, R ₁₆ is optionally substituted alkoxyl. In certain embodiments, R ₁₆ is C _1-6 alkoxyl. In certain embodiments, R ₁₆ is methoxyl. In certain embodiments, R ₁₆ is ethoxyl. In certain embodiments, R ₁₆ is propoxyl. In certain embodiments, R ₁₆ is butoxyl.

In compounds of Formula (II-J) or (II-J′), R ₁₇ is–OR ₁₈ or–N(R ^N1 ) ₂ . In certain embodiments, R ₁₇ is–OR ₁₈ . In certain embodiments, R ₁₇ is–OH. In certain embodiments, R ₁₇ is–O–alkyl. In certain embodiments, R ₁₇ is–O–(C _1-6 alkyl). In certain embodiments, R ₁₇ is– OMe. In certain embodiments, R ₁₇ is–OEt. In certain embodiments, R ₁₇ is–OPr. In certain embodiments, R ₁₇ is–OBu. In certain embodiments, R ₁₇ is–O–arylalkyl. In certain embodiments, R ₁₇ is–O–phenalkyl. In certain embodiments, R ₁₇ is–O–Bn. In certain embodiments, R ₁₇ is–O–phenethyl. In certain embodiments, R ₁₇ is–N(OH)R ^N1 . In certain embodiments, R ₁₇ is–N(OH)–alkyl. In certain embodiments, R ₁₇ is–N(OH)–(C _1-6 alkyl). In certain embodiments, R ₁₇ is–N(OH)–(CH ₂ ) _s –N(OH)C(=O)R ₂₀ . In certain embodiments, R ₁₇ is–N(R ^N1 ) ₂ , wherein each instance of is R ^N1 is independently hydrogen or optionally substituted alkyl.

[00287] In compounds of Formula (II-J) or (II-J′), R ₁₈ is hydrogen, optionally substituted alkyl, or optionally substituted arylalkyl. In certain embodiments, R ₁₈ is hydrogen. In certain embodiments, R ₁₈ is optionally substituted alkyl. In certain embodiments, R ₁₈ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₁₈ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₁₈ is methyl. In certain embodiments, R ₁₈ is ethyl. In certain embodiments, R ₁₈ is propyl. In certain embodiments, R ₁₈ is butyl. In certain embodiments, R ₁₈ is arylalkyl. In certain embodiments, R ₁₈ is aryl–(C _1-6 alkyl). In certain embodiments, R ₁₈ is phenyl–(C _1-6 alkyl). In certain embodiments, R ₁₈ is Bn. In certain embodiments, R ₁₈ is phenethyl.

[00288] In compounds of Formula (II-J) or (II-J′), R ₁₉ is alkyl or–(CH ₂ ) _s –

N(OH)C(=O)R ₂₀ .

[00289] In certain embodiments, R ₁₉ is optionally substituted alkyl. In certain

embodiments, R ₁₉ is optionally substituted C _1-6 alkyl.. In certain embodiments, R ₁₉ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₁₉ is methyl. In certain embodiments, R ₁₉ is ethyl. In certain embodiments, R ₁₉ is propyl. In certain embodiments, R ₁₉ is butyl. In certain embodiments, R ₁₉ is–(CH ₂ ) _s –N(OH)C(=O)R ₂₀ .

[00290] In compounds of Formula (II-J) or (II-J′), s is an integer from 1 to 8, inclusise. In certain embodiments, s is 1. In certain embodiments, s is 2. In certain embodiments, s is 3. In certain embodiments, s is 4. In certain embodiments, s is 5. In certain embodiments, s is 6. In certain embodiments, s is 7. In certain embodiments, s is 8.

[00291] In compounds of Formula (II-J) or (II-J′), R ₂₀ is optionally substituted alkyl. In certain embodiments, R ₂₀ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₂₀ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₂₀ is methyl. In certain embodiments, R ₂₀ is ethyl. In certain embodiments, R ₂₀ is propyl. In certain embodiments, R ₂₀ is butyl.

[00292] In compounds of Formula (II-J) or (II-J′), R ₂₁ is hydrogen or optionally substituted alkyl. In certain embodiments, R ₂₁ is hydrogen. In certain embodiments, R ₂₁ is optionally substituted alkyl. In certain embodiments, R ₂₁ is optionally substituted C _1-6 alkyl. In certain embodiments, R ₂₁ is unsubstituted C _1-6 alkyl. In certain embodiments, R ₂₁ is methyl. In certain embodiments, R ₂₁ is ethyl. In certain embodiments, R ₂₁ is propyl. In certain embodiments, R ₂₁ is butyl.

[00293] In compounds of Formula (II-J) or (II-J′), each occurrence of R ₂₂ is

independently null, hydrogen, or optionally substituted alkyl. In certain embodiments, at least one R ₂₂ is null. In certain embodiments, at least one R ₂₂ is hydrogen. In certain embodiments, at least one R ₂₂ is optionally substituted alkyl. In certain embodiments, at least one R ₂₂ is optionally substituted C _1-6 alkyl. In certain embodiments, at least one R ₂₂ is unsubstituted C _1-6 alkyl. In certain embodiments, at least one R ₂₂ is methyl. In certain embodiments, at least one R ₂₂ is ethyl. In certain embodiments, at least one R ₂₂ is propyl. In certain embodiments, at least one R ₂₂ is butyl.

[00294] In compounds of Formula (II-J) or (II-J′), each occurrence of R ₂₃ is

independently null, hydrogen, or optionally substituted alkyl. In certain embodiments, at least one R ₂₃ is null. In certain embodiments, at least one R ₂₃ is hydrogen. In certain embodiments, at least one R ₂₃ is optionally substituted alkyl. In certain embodiments, at least one R ₂₃ is optionally substituted C _1-6 alkyl. In certain embodiments, at least one R ₂₃ is unsubstituted C _1-6 alkyl. In certain embodiments, at least one R ₂₃ is methyl. In certain embodiments, at least one R ₂₃ is ethyl. In certain embodiments, at least one R ₂₃ is propyl. In certain embodiments, at least one R ₂₃ is butyl. [00295] In certain embodiments, the compound of Formula (II-J) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00296] In certain embodiments, the compound of Formula (II-J) is of the formula:

,

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00297] The compound of Formula (II-J) may have one or more chiral centers. In certain embodiments, the compound of Formula (II-J) is of Formula (II-K):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00298] In certain embodiments, the compound of Formula (II-J) is of the formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00299] In certain embodiments, the compound of Formula (II-J) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00300] In certain embodiments the compound of Formula (II-J) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00301] certain embodiments, the compound of Formula (II-J) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00302] In certain embodiments the compound of Formula (II-J) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00303] In certain embodiments, the compound of Formula (II-J') is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00304] In certain embodiments, the compound of Formula (II-J′) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00305] In certain embodiments, the compound of Formula (II-J') is of one of the following formul

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00306] In certain embodiments, the compound of Formula (II-J') is of one of the following formul

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00307] In certain embodiments, the compound of Formula (II-J′) is of one of the following formulae:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00308] In certain embodiments, the compound of Formula (II-J′) is of one of the following formulae:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00309] In certain embodiments, the compound of Formula (II-J′) is of the following formula:

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof, wherein each instance of R ^N2 and R ^N3 is independently hydrogen, optionally substituted alkyl, or optionally substituted acyl.

[00310] In certain embodiments, the compound of Formula (II-J′) is of the following formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof, wherein

each instance of R ^N2 and R ^N3 is independently hydrogen, optionally substituted alkyl, or optionally substituted acyl;

each instance of R ^p and R ^q is independently hydrogen, halogen, -CN, -NO ₂ , -N ₃ , optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted phenyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted alkoxy, an optionally substituted amino group, or optionally substituted acyl,

p1 is 0 or an integer of 1 to 5, inclusive; and

q1 is 0 or an integer of 1 to 5, inclusive. [00311] In certain embodiments, the compound of Formula (II-J′) is of the following formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00312] In certain embodiments, the compound of Formula (II-J′) is of the following formulae:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00313] The compounds of the invention may be provided in various salts forms. In certain embodiments, the inventive compounds are provided as alkali metal salts. In certain embodiments, the chelating agents as provided herein are provided as alkaline earth metal salts. In certain embodiments, when R ₉ is–OH, the compound may be provided as a carboxylate salt with a positively charged counterion. In certain embodiments, the counterion is betaine, choline hydroxide, diethanolamine, diethylamine, ethanolamine,

hydroxyethylmorpholine, 4-(2-hydroxyethyl morpholine), 1-(2-hydroxyethyl pyrrolidine), 1- (2-hydroxyethyl)-piperidine, 1,2-EDSA, HCl, H ₂ SO ₄ , MSA, p-TSA, hydroxyethyl pyrroldine, imidazone, lysine (e.g., L-lysine), arginine (e.g., L-arginine), histidine (e.g., L- histidine) N-methyl-D-glucamine (NMG), N, N′-dibenzyl-ethylenediamine, N, N′-diethyl- ethanolamine, triethanolamine, tromethamine, calcium (e.g., Ca(OH) ₂ ), magnesium (e.g., Mg(OH) ₂ , magnesium acetate), potassium (e.g., KOH, potassium 2-ethylhexanoate), sodium (e.g., NaOH, sodium acetate, sodium 2-ethylhexanoate), zinc (e.g., Zn(OH) ₂ , zinc acetate), Zn(OH) ₂ /Mg(OH) ₂ , EDA, or piperazinyl. In certain embodiments, the counterion is lysine. In certain embodiments, the counterion is N-methyl-D-glucamine (NMG). In certain

embodiments, the counterion is tromethamine. In certain embodiments, the counterion is calcium. In certain embodiments, the counterion is magnesium. In certain embodiments, the counterion is cesium. In certain embodiments, the counterion is potassium. In certain embodiments, the counterion is sodium. In certain embodiments, the counterion is lithium. In certain embodiments, the counterion is zinc. In certain embodiments, the counterion is piperzine. In certain embodiments, the counterion is MgOH ⁺ . In certain embodiments, the counterion is ZnOH ⁺ .

[00314] In certain embodiments, a polymorph of a salt of a compound of the invention is provided. In certain embodiments, a polymorph of a magnesium salt of a compound of the invention is provided. In certain embodiments, a polymorph of a sodium salt of a compound of the invention is provided. In certain embodiments, a polymorph of a salt of a carboxylate compound of the invention, wherein R ₉ is–OH, is provided. In certain embodiments, a polymorph of a magnesium salt of a carboxylate compound of the invention, wherein R ₉ is– OH, is provided. In certain embodiments, a polymorph of a sodium salt of a carboxylate compound of the invention, wherein R ₉ is–OH, is provided.

[00315] The cation and anion in a salt disclosed herein may combine in a 1:1 molar ratio. Other molar ratios (e.g., 1:1.5, 1:2, 1:6, and 2:1) are also possible. Salts shown herein may be, for the sole purpose of convenience in notation, shown in a 1:1 ratio. All possible

stoichiometric arrangements are encompassed by the scope of the present invention.

[00316] In certain embodiments, a salt of a compound of any one of the Formulae (I-P-1)- ( I-P-4) is provided. In certain embodiments, the present invention provides a sodium salt of any one of the Formulae (I-P-1)-( I-P-4) as shown in the formula:

, , or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00317] As used herein, MM refers to a metal or metal complex cation. In certain embodiments, MM is a Group IA metal cation. In certain embodiments, MM is Na. In certain embodiments, MM is K. In certain embodiments, MM is a Group IIA metal cation complex. In certain embodiments, MM is Mg(OH).

[00318] In certain embodiments, the compound of Formula (II-A) is of the Formula (II-I- i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00319] In certain embodiments, a salt of a compound of the Formula (II-i-1) is provided. In certain embodiments, a salt of the Formula (II-i-1) is provided as shown in the Formula (II-i-1-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00320] In certain embodiments, the compound of Formula (II-A) is of the Formula (II-I- 1):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00321] In certain embodiments, a salt of a compound of the Formula (II-I-1) is provided. In certain embodiments, a salt of the Formula (II-I-1) is provided as shown in the Formula (II-I-1-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00322] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-1-ii):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00323] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-1-iii):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00324] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-1-iv):

( ), or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00325] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00326] In certain embodiments, a salt of a compound of the Formula (II-I-2) is provided. In certain embodiments, a salt of the Formula (II-I-2) is provided as shown in the Formula (II-I-2-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00327] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-2-ii):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00328] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-2-iii):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00329] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-2-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00330] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-3):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00331] In certain embodiments, a salt of a compound of the Formula (II-I-3) is provided. In certain embodiments, a salt of the Formula (II-I-3) is provided as shown in the Formula (II-I-3-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00332] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-3-ii):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00333] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-3-iii):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00334] In certain embodiments, the compound of the Formula (II-A) is of the Formula (II-I-3-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00335] In certain embodiments, the compound of Formula (II-A) is of the formula:

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00336] In certain embodiments, the compound of Formula (II-A) is of the formula:

,

,

,

, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00337] In certain embodiments, the salt of a compound of Formula (II-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00338] In certain embodiments, the compound of Formula (II-A) is of the formulae:

,

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00339] In certain embodiments, the compound of Formula (II-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00340] In certain embodiments, the salt of a compound of Formula (II-A) is of the formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00341] Additional exemplary compounds of Formula (A) include, but are not limited to:

,

and pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, hydrates, and polymorphs thereof.

[00342] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 1):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00343] In certain embodiments, a salt of a compound of the Formula (II-J-1) is provided. In certain embodiments, a salt of the Formula (II-J-1) is provided as shown in the Formula (II-J-1-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00344] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-1-ii) to (II-J-1-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00345] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 2):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00346] In certain embodiments, a salt of a compound of the Formula (II-J-2) is provided. In certain embodiments, a salt of the Formula (II-J-2) is provided as shown in the Formula (II-J-2-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00347] In certain embodiments, the compound of the Formula (II- A) is of any one of the Formulae (II-J-2-ii) to (II-J-2-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof

[00348] In certain embodiments, the compound of Formula (II- J) is of the Formula (II- J- 3):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00349] In certain embodiments, a salt of a compound of the Formula (II-J-3) is provided. In certain embodiments, a salt of the Formula (II-J-3) is provided as shown in the Formula (II-J-3-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00350] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-3-ii) to (II-J-3-iv):

,

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00351] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 4):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00352] In certain embodiments, a salt of a compound of the Formula (II-J-4) is provided. In certain embodiments, a salt of the Formula (II-J-4) is provided as shown in the Formula (II-J-4-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00353] In certain embodiments, the compound of the Formula (A) is of any one of the Formulae (II-J-4-ii) to (II-J-4-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00354] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J 5):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00355] In certain embodiments, a salt of a compound of the Formula (II-J-5) is provided. In certain embodiments, a salt of the Formula (II-J-5) is provided as shown in the Formula (II-J-5-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00356] In certain embodiments, the compound of the Formula (II- A) is of any one of the Formulae (II- -5-ii) to (II-J-5-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00357] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 6):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00358] In certain embodiments, a salt of a compound of the Formula (II-J-6) is provided. In certain embodiments, a salt of the Formula (II-J-6) is provided as shown in the Formula (II-J-6-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00359] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-6-ii) to (II-J-6-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00360] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 7):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00361] In certain embodiments, a salt of a compound of the Formula (II-J-7) is provided. In certain embodiments, a salt of the Formula (II-J-7) is provided as shown in the Formula (II-J-7-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00362] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-7-ii) to (II-J-7-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00363] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 8):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00364] In certain embodiments, a salt of a compound of the Formula (II-J-8) is provided. In certain embodiments, a salt of the Formula (II-J-8) is provided as shown in the Formula (II-J-8-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00365] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-8-ii) to (II-J-8-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00366] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 9):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00367] In certain embodiments, a salt of a compound of the Formula (II-J-9) is provided. In certain embodiments, a salt of the Formula (II-J-9) is provided as shown in the Formula (II-J-9-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00368] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-9-ii) to (II-J-9-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00369] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 10):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00370] In certain embodiments, a salt of a compound of the Formula (II-J-10) is provided. In certain embodiments, a salt of the Formula (II-J-10) is provided as shown in the Formula (II-J-10-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00371] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-10-ii) to (II-J-10-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00372] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 11):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00373] In certain embodiments, a salt of a compound of the Formula (II-J-11) is provided. In certain embodiments, a salt of the Formula (II-J-11) is provided as shown in the Formula (II-J-11-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00374] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-11-ii) to (II-J-11-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof [00375] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 12):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00376] In certain embodiments, a salt of a compound of the Formula (II-J-12) is provided. In certain embodiments, a salt of the Formula (II-J-12) is provided as shown in the Formu -J-12-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00377] In certain embodiments, the compound of the Formula (A) is of any one of the Formulae (II-J-12-ii -J-12-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00378] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 13):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00379] In certain embodiments, a salt of a compound of the Formula (II-J-13) is provided. In certain embodiments, a salt of the Formula (II-J-13) is provided as shown Formula (II- -13-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00380] In certain embodiments, the compound of the Formula (II- A) is of any one of the Formulae (II-J-13-ii) to (II-J-13-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00381] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 14):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00382] In certain embodiments, a salt of a compound of the Formula (II-J-14) is provided. In certain embodiments, a salt of the Formula (II-J-14) is provided as shown in the Formula (II-J-14-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00383] In certain embodiments, the compound of the Formula (A) is of any one of the Formulae (II-J-14-ii) to (II-J-14-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00384] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 15):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00385] In certain embodiments, a salt of a compound of the Formula (II-J-15) is provided. In certain embodiments, a salt of the Formula (II-J-15) is provided as shown in the Formula (II-J-15-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00386] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-15-ii) to (II-J-15-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00387] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 16):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00388] In certain embodiments, a salt of a compound of the Formula (II-J-16) is provided. In certain embodiments, a salt of the Formula (II-J-16) is provided as shown Formula (I -J-16-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00389] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-16-ii) to (II-J-16-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00390] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 17):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00391] In certain embodiments, a salt of a compound of the Formula (II-J-17) is provided. In certain embodiments, a salt of the Formula (II-J-17) is provided as shown in the Formula (II-J-17-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00392] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-17-ii) to (II-J-17-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00393] In certain embodiments, the compound of Formula (II- J) is of the Formula (II- J- 18):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00394] In certain embodiments, a salt of a compound of the Formula (II-J-18) is provided. In certain embodiments, a salt of the Formula (II-J-18) is provided as shown in the Formula (II-J-18-i :

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00395] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-18-ii) to (II-J-18-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00396] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 19):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00397] In certain embodiments, a salt of a compound of the Formula (II-J-19) is provided. In certain embodiments, a salt of the Formula (II-J-19) is provided as shown in the Formula (II-J-19-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00398] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-19-ii) to (II-J-19-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00399] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 20):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00400] In certain embodiments, a salt of a compound of the Formula (II-J-20) is provided. In certain embodiments, a salt of the Formula (II-J-20) is provided as shown in the Formula (II-J-20-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00401] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-20-ii) to (II-J-20-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00402] In certain embodiments, the compound of Formula (II-J) is of the Formula (II-J- 21):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00403] In certain embodiments, a salt of a compound of the Formula (II-J-21) is provided. In certain embodiments, a salt of the Formula (II-J-21) is provided as shown in the Formula (II-J-21-i):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00404] In certain embodiments, the compound of the Formula (II-A) is of any one of the Formulae (II-J-21-ii) to (II-J-21-iv):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00405] In certain embodiments, the compound used in the inventive method is a compound of Formula (III-A)

or a pharmaceutically acceptable salt thereof,

wherein:

each instance of R ^H1 and R ^H2 is independently hydrogen, halo, -CN, -NO ₂ , halogen, optionally substituted alkyl, -OR ^HA , -N(R ^HB ) ₂ , or–CO ₂ R ^HA ;

each occurrence of R ^HA is independently hydrogen, optionally substituted alkyl, or an oxygen protecting group;

each occurrence of R ^HB is independently hydrogen, optionally substituted alkyl, or an amino protecting group;

each of R ^H3 , R ^H4 , R ^H5 , and R ^H6 is independently hydrogen, halo, optionally substituted alkyl, or optionally substituted alkoxyl;

or R ^H3 and R ^H4 are taken together to form =O;

or R ^H5 and R ^H6 are taken together to form =O; each R ^H7 and R ^H8 is independently hydrogen, optionally substituted alkyl, or a nitrogen protecting group;

L ^H is an optionally substituted C _1-8 alkylene or optionally substituted heteroalkylene; and

each of h and g is independently 0, 1, 2, 3, 4, or 5.

[00406] In certain embodiments, the compound used in the inventive method is a compound of Formula (III-A-i)

( ),

or a pharmaceutically acceptable salt thereof.

[00407] In certain embodiments, the compound used in the inventive method is a compound of Formula (III-A-ii):

or a pharmaceutically acceptable salt thereof.

[00408] As generally defined herein, R ^H1 is hydrogen, halo, -CN, -NO ₂ , halogen, optionally substituted alkyl, -OR ^A , -N(R ^B ) ₂ , or–CO ₂ R ^A . In certain embodiments, R ^H1 is hydrogen. In certain embodiments, R ^H1 is halo. In certain embodiments, R ^H1 is optionally substituted alkyl. In certain embodiments, R ^H1 is unsubstituted alkyl. In certain embodiments, R ^H1 is methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, or t-butyl. In certain embodiments, R ^H1 is -OR ^A . In certain embodiments, R ^H1 is -OH. In certain embodiments, R ^H1 is–CO ₂ R ^A . In certain embodiments, R ^H1 is–CO ₂ CH ₃ .

[00409] As generally defined herein, R ^H2 is hydrogen, halo, -CN, -NO ₂ , halogen, optionally substituted alkyl, -OR ^HA , -N(R ^HB ) ₂ , or–CO ₂ R ^HA . In certain embodiments, R ^H2 is hydrogen. In certain embodiments, R ^H2 is halo. In certain embodiments, R ^H2 is optionally substituted alkyl. In certain embodiments, R ^H2 is unsubstituted alkyl. In certain embodiments, R ^H2 is methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, or t-butyl. In certain embodiments, R ^H2 is -OR ^HA . In certain embodiments, R ^H2 is -OH. In certain embodiments, R ^H2 is–CO ₂ R ^HA . In certain embodiments, R ^H2 is–CO ₂ CH ₃ . [00410] As generally defined herein, L ^H is an optionally substituted C _1-8 alkylene or optionally substituted heteroalkylene. In certain embodiments, L ^H is an optionally substituted C _1-8 alkylene. In certain embodiments, L ^H is unsubstituted C _1-8 alkylene. In certain embodiments, L ^H is–CH ₂ –. In certain embodiments, L ^H is–(CH ₂ ) ₂ –. In certain embodiments, L ^H is–(CH ₂ ) ₃ –. In certain embodiments, L ^H is substituted C _1-8 alkylene. In certain

embodiments, L ^H is C _1-8 alkylene substituted by an hydroxyl group. In certain embodiments, L ^H is–CH ₂ CH(OH)CH ₂ –. In certain embodiments, L ^H is an optionally substituted

heteroalkylene. In certain embodiments, L ^H is–(CH ₂ ) _1-5 -NR ^HN -(CH ₂ ) _1-5 -, wherein R ^HN is hydrogen, optionally substituted alkyl, optionally substituted acyl, or a nitrogen protecting group. In certain embodiments, L ^H is–(CH ₂ ) _1-5 -NH-(CH ₂ ) _1-5 -, wherein R ^HN is hydrogen, optionally substituted alkyl, optionally substituted acyl, or a nitrogen protecting group.

[00411] As generally defined herein, R ^HA is independently hydrogen, optionally substituted alkyl, or an oxygen protecting group. In certain embodiments, R ^HA is hydrogen. In certain embodiments, R ^HA is optionally substituted alkyl. In certain embodiments, R ^HA is unsubstituted alkyl (e.g., methyl or ethyl). In certain embodiments, R ^HA is substituted alkyl. In certain embodiments, R ^HA is an oxygen protecting group (e.g., acyl or Boc).

[00412] As generally defined herein, R ^HB is independently hydrogen, optionally substituted alkyl, or an amino protecting group. In certain embodiments, R ^HB is hydrogen. In certain embodiments, R ^HB is optionally substituted alkyl. In certain embodiments, R ^HB is unsubstituted alkyl (e.g., methyl or ethyl). In certain embodiments, R ^HB is substituted alkyl. In certain embodiments, R ^HB is a nitrogen protecting group (e.g., acyl or Fmoc).

[00413] In certain embodiments, h is 0. In certain embodiments, h is 1. In certain embodiments, h is 2. In certain embodiments, h is 3. In certain embodiments, h is 4. In certain embodiments, his 5.

[00414] In certain embodiments, g is 0. In certain embodiments, g is 1. In certain embodiments, g is 2. In certain embodiments, g is 3. In certain embodiments, g is 4. In certain embodiments, g is 5.

[00415] In certain embodiments, the compound of Formula (III-A) is of Formula (III-B):

or a pharmaceutically acceptable salt thereof.

[00416] In certain embodiments, the compound of Formula (III-A) is of Formula (III-B-i):

or a pharmaceutically acceptable salt thereof.

[00417] In certain embodiments, R ^H1 and R ^H2 are different. In certain embodiments, R ^H1 and R ^H2 are the same. In certain embodiments, both R ^H1 and R ^H2 are hydrogen.

[00418] In certain embodiments, the compound of Formula (III-A) is of Formula (III-B- ii):

wherein M is a monovalent, pharmaceutically acceptable cation.

[00419] As generally defined herein, M is a monovalent, pharmaceutically acceptable cation. The phrase“pharmaceutically acceptable” means that the cation is suitable for administration to a subject. In certain embodiments, M is an inorganic cation. In certain embodiments, M is an alkali metal cation. In certain embodiments, M is Li ⁺ , Na ⁺ , K ⁺ , or Cs ⁺ . In certain embodiments, M is Na ⁺ . In certain embodiments, M is K ⁺ . In certain embodiments, M is NH ⁺

4 . In certain embodiments, M is (MgOH) ⁺ . [00420] In certain embodiments, the compound of the Formula (III-A) is of the following formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00421] In certain embodiments, the compound of the Formula (III-A) is of the following formula:

.

[00422] In certain embodiments, the compound of the Formula (III-A) is of the following formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof. [00423] In certain embodiments, the compound of the Formula (III-A) is of the following formula:

or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof.

[00424] In certain embodiments, the compound used in the inventive method is a compound of Formula (III-E):

or a pharmaceutically acceptable salt thereof.

[00425] In certain embodiments, the compound used in the inventive method is a compound of Formula (III-E-i)

or a pharmaceutically acceptable salt thereof.

[00426] In certain embodiments, the compound used in the inventive method is a compound of Formula (III-E-ii)

or a pharmaceutically acceptable salt thereof, wherein R ^HN is hydrogen, optionally substituted alkyl, optionally substituted acyl, or a nitrogen protecting group.

[00427] In certain embodiments, the compound used in the inventive method is a compound of the following formula:

or a pharmaceutically acceptable salt thereof.

[00428] In certain embodiments, the compound used in the inventive method is a compound of the following formula:

, or a pharmaceutically acceptable salt thereof.

[00429] In certain embodiments, the compound used in the inventive method is a compound of the following formula:

[00430] In certain embodiments, the compound used in the inventive method is a compound of the following formula:

. Compositions, Kits, and Administration

[00431] In one aspect, the invention also provides a pharmaceutical composition comprising a compound of any one of Formulae (I-A)-(III-A), or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or a polymorph thereof, and optionally a carrier for treating or preventing an infectious disease and/or biofilm formation. The pharmaceutical composition may further comprise another antimicrobial agent (e.g., antibiotics).

[00432] Infectious diseases are typically caused by microbial pathogens (e.g., viruses, viroids, prions, microorganisms such as bacteria, nematodes such as roundworms and pinworms, arthropods such as ticks, mites, fleas, and lice, fungi such as ringworm, and parasites such as protozoa, multicellular parasites, or tapeworms) into the cells (“host cells”) of a subject (“host”). In certain embodiments, the infectious disease is a bacterial infection. In certain embodiments, the infectious disease is a mycobacterial infection. In certain embodiments, the infectious disease is a viral infection. In certain embodiments, the infectious disease is a parasitic infection. In certain embodiments, the infectious disease is a multicellular-parasitic infection. In certain embodiments, the infectious disease is a fungal infection. In certain embodiments, the infectious disease is a protozoan infection.

[00433] The present invention provides compositions for use to treat or prevent biofilm formation comprising a compound as described herein, and salts, tautomers, stereoisomers, solvates, hydrates, and polymorphs thereof, and optionally a carrier. In certain embodiments, the compound or a salt thereof is provided in an effective amount in the composition. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount. In certain embodiments, the effective amount is a clean-effective amount. In certain embodiments, the effective amount is to prevent biofilm formation. In certain embodiments, the effective amount is to remove biofilm formed. In certain embodiments, the provided composition further comprises a surfactant. In certain embodiments, the surfactant is selected from the group consisting of anionic, nonionic, amphoteric, biological surfactants, and mixtures thereof. In certain embodiments, the provided composition further comprises one or more disinfecting agents. Disinfecting agents can comprise alcohols (such as ethanol or isopropanol), aldehydes (such as glutaraldehyde), oxidizing agents (such as sodium hypochlorite, calcium hypochlorite, chloramine, hydrogen peroxide, iodine, peracetic acid, performic acid, potassium permanganate, and postassium peroxymonosulfate), phenolics (such as phenol, o-phenylphenol, chloroxylenol, hexachlorophene, and thymol). A disinfectant can be a spray or a liquid. A disinfectant can be concentrated or ready-to-use. A disinfectant can be for commercial or household use. A composition of the invention can also be incorporated into household disinfectants, laundry detergent, and household cleaning solutions

[00434] In certain embodiments, the provided compositions can be useful for

decontaminating, inhibiting growth, or preventing growth on surfaces where microorganisms form a biofilm (e.g., tubing). Therefore, in some embodiments, a method of the invention includes rinsing or decontaminating a surface by contacting the surface with a composition of the invention. Further, in some embodiments, a method of the invention includes inhibiting biofilm growth or preventing biofilm growth by incorporating, coating, impregnating, flusing, or rinsing an object with the provided composition. In some embodiments, a composition of the invention can be incorporated into a surface by coating or impregnating the surface of an object.

[00435] In certain embodiments, the present invention provides pharmaceutical compositions comprising a compound as described herein, and pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, hydrates, and polymorphs thereof, and optionally a pharmaceutically acceptable carrier. In certain embodiments, the present invention provides pharmaceutical compositions for use to treat or prevent an infectious disease comprising a compound as described herein, and pharmaceutically acceptable salts, tautomers,

stereoisomers, solvates, hydrates, and polymorphs thereof, and optionally a pharmaceutically acceptable carrier. In certain embodiments, the present invention provides pharmaceutical compositions for use to treat or prevent biofilm formation comprising a compound as described herein, and pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, hydrates, and polymorphs thereof, and optionally a pharmaceutically acceptable carrier. In certain embodiments, the compound or a pharmaceutically acceptable salt thereof, is provided in an effective amount in the pharmaceutical composition. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount.

[00436] In certain embodiments, the provided compositions or pharmaceutical

compositions further comprise an additional therapeutically active agent. In certain embodimetns, the antimicrobial agent is selected from the group consisting of biocides, fungicides, antibiotics, and mixtures thereof. In certain embodimetns, the antimicrobial agent is an antibiotic. [00437] Exemplary additional therapeutically active agents include, but are not limited to, antibacterial agents (e.g., antibiotics), antiviral agents, fungicides, protozoacides,

parasiticides, anesthetics, steroidal or non–steroidal anti–inflammatory agents, antihistamine, antigens, vaccines, antibodies, decongestant, sedatives, opioids, pain–relieving agents, analgesics, anti–pyretics, hormones, prostaglandins, etc. Therapeutically active agents include small organic molecules such as drug compounds (e.g., compounds approved by the US Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, and vitamins.

[00438] In certain embodimetns, the additional therapeutically active agent is an antibacterial agent. Exemplary antibacterial agents for uses in combination with a chelating agent as described herein include, but are not limited to, (-)-Florfenicol, Acetylsulfisoxazole, Actinonin, Amikacin sulfate, Benzethonium chloride, Cephalosporins (e.g., 7- Aminocephalosporanic acid, 7-Aminodeacetoxycephalosporanic acid, Cefaclor, Cefadroxil, Cefamandole, Cefazolin, Cefepime, Cefixime, Cefmenoxime, Cefmetazole, Cefoperazone, Cefotaxime, Cefotetan, Cefotiam, Cefoxitin, Cefpirome, Cefpodoxime proxetil, Cefsulodin, Cefsulodin sodium, Ceftazidime, Ceftizoxime, Ceftriaxone, Cefuroxime, Cephalexin, Cephaloridine, Cephalosporin C, Cephalothin, Cephalothin sodium, Cephapirin, Cephradine), Cetrimide Chelerythrine, Chlorhexidine(e.g., Chlorhexidine gluconate), Chlorhexidine acetate, Chlorhexidine gluconate, Chlorothalonil, Ciprofloxacin (e.g., Enrofloxacin),

Clarithromycin, Clavulanic acid (e.g., Amoxicillin-clavulanic acid), Clindamycin, Co- Trimoxazole, Dichlorophene, Didecyldimethylammonium chloride, Dihydrostreptomycin, Enoxacin, Ethambutol, Fleroxacin, Furazolidone, Grepafloxacin hydrochloride,

Levofloxacin, Linezolid, Lomefloxacin, Methylisothiazolinone, Monolaurin, Oxolinic acid, Pefloxacin, Penicillin (e.g., 6-Aminopenicillanic acid, Amoxicillin (e.g., Amoxicillin- clavulanic acid), Ampicillin, Ampicillin sodium, Azlocillin, Carbenicillin, Cefoxitin, Cephaloridine, Cloxacillin, Dicloxacillin, Mecillinam, Methicillin, Mezlocillin, Nafcillin, Oxacillin, Penicillin G, Penicillin G potassium, Penicillin G procaine Penicillin G sodium, Penicillin V, Piperacillin, Piperacillin-tazobactam, Sulbactam, Tazobactam, Ticarcillin), Povidone-iodine, Rotproofing agents, Salinomycin, Sparfloxacin, Spirocheticides (e.g., Arsphenamine, Neoarsphenamine), Sulbactam, Sulfaquinoxaline, Tetracyclines (e.g., Achromycin V, Demeclocycline, Doxycycline, Doxycycline monohydrate, Minocycline, Oxytetracycline, Oxytetracycline hydrochloride, Tetracycline, Tetracycline hydrochloride), Thiamphenicol, Tinidazole, Triclosan, Trovafloxacin, Tuberculostatics (e.g., 4- Aminosalicylic acid, AZD 5847, Aminosalicylic acid, Ethionamide), Vidarabine, Zinc pyrithione, Zirconium phosphate.

[00439] In certain embodimetns, the additional therapeutically active agent is an antiviral agent. Exemplary antiviral agents for uses in combination with a chelating agent as described herein include, but are not limited to, (-)-Oseltamivir, β-D-Ribofuranose, 1-acetate 2,3,5- tribenzoate, 1-Docosanol, 2-Amino-6-chloropurine, 5-Iodo-2'-deoxyuridine, 6-Chloropurine, Abacavir sulfate, Abacavir-epivir mixture, Acyclovir, Acyclovir sodium, Adefovir dipivoxil, Amantadine (e.g., Amantadine hydrochloride), Amantadine hydrochloride, Anti-HIV agents (e.g., Abacavir, Amprenavir, Atazanavir, Azidothymidine, Bryostatin (e.g., Bryostatin 1, Bryostatin 10, Bryostatin 11, Bryostatin 12, Bryostatin 13, Bryostatin 14, Bryostatin 15, Bryostatin 16, Bryostatin 17, Bryostatin 18, Bryostatin 19, Bryostatin 2, Bryostatin 20, Bryostatin 3, Bryostatin 4, Bryostatin 5, Bryostatin 6, Bryostatin 7, Bryostatin 8, Bryostatin 9), Dideoxycytidine, Dideoxyinosine, Efavirenz, Indinavir, Lamivudine, Lopinavir,

Nevirapine, Ritonavir, Saquinavir, Stavudine, Tenofovir), Azauridine, ombivir,

Deoxynojirimycin, Docosanol, Fomivirsen sodium, Foscarnet, Ganciclovir, Integrase inhibitors (e.g., 5CITEP, Chloropeptin I, Complestatin, Dolutegravir, Elvitegravir, L 708906, L 731988, MK 2048, Raltegravir, Raltegravir potassium), MK 5172, MK 8742, Palivizumab, Pegylated interferon alfa-2b, Phosphonoacetic acid, Ribavirin, Simeprevir, Sofosbuvir, Tubercidin, Vidarabine, Virus entry inhibitors (e.g., Enfuvirtide, Maraviroc).

[00440] In certain embodimetns, the additional therapeutically active agent is a fungicide. Exemplary fungicides for uses in combination with a chelating agent as described herein include, but are not limited to, (-)-Fumagillin, (-)-Metalaxyl, 1,2, 5-Fluorocytosine,

Acrisorcin, Anilazine, Antifouling agents, Azoxystrobin, Benomyl, Bordeaux mixture, Captan, Carbendazim, Caspofungin acetate, Chlorothalonil, Clotrimazole, Dichlofluanid, Dinocap, Dodine, Fenhexamid, Fenpropimorph, Ferbam, Fluconazole, Fosetyl Al,

Griseofulvin, Guanidines (e.g., Agmatine, Amiloride hydrochloride, Biguanides (e.g., Imidodicarbonimidic diamide, N,N-dimethyl-,hydrochloride (1:1)(e.g., Metformin hydrochloride), Metformin), Cimetidine, Guanethidine, Guanfacine, Guanidine,

Guanidinium, Methylguanidine, Sulfaguanidine), Iprobenfos, Iprodione, Isoprothiolane, Itraconazole, Ketoconazole, Mancozeb, Metalaxyl, Metiram, Miconazole, Natamycin, Nystatin, Oxycarboxine, Pentachloronitrobenzene, Prochloraz, Procymidone, Propiconazole, Pyrazophos, Reduced viscotoxin A3, Salicylanilide, Tebuconazole, Terbinafine,

Thiabendazole, Thiophanate, Thiophanate methyl, Triadimefon, Vinclozolin, Voriconazole.

[00441] In certain embodimetns, the additional therapeutically active agent is a

protozoacide. Exemplary protozoacides for uses in combination with a chelating agent as described herein include, but are not limited to, Amebicides, Antimalarials (e.g., Artemisinin, Chloroquine (e.g., Chloroquine phosphate), Mefloquine, Sulfadoxine), Coccidiostats, Leishmanicides, Trichomonacides, Trypanosomicides (e.g., Eflornithine).

[00442] In certain embodiments, the additional therapeutically active agent is an antibiotic. Exemplary antibiotics for uses in combination with a chelating agent as described herein include, but are not limited to, Abamectin, Actinomycin (e.g., Actinomycin A, Actinomycin C, Actinomycin D, Aurantin), Adriamycin, Alatrofloxacin mesylate, Amikacin sulfate, Aminosalicylic acid, Anthracyclines (e.g., Aclarubicin, Adriamycin, Doxorubicin,

Epirubicin, Idarubicin), Antimycin (e.g., Antimycin A), Avermectin, BAL 30072, Bacitracin, Bleomycin, Cephalosporins (e.g., 7-Aminocephalosporanic acid, 7- Aminodeacetoxycephalosporanic acid, Cefaclor, Cefadroxil, Cefamandole, Cefazolin, Cefepime, Cefixime, Cefmenoxime, Cefmetazole, Cefoperazone, Cefotaxime, Cefotetan, Cefotiam, Cefoxitin, Cefpirome, Cefpodoxime proxetil, Cefsulodin, Cefsulodin sodium, Ceftazidime, Ceftizoxime, Ceftriaxone, Cefuroxime, Cephalexin, Cephaloridine,

Cephalosporin C, Cephalothin, Cephalothin sodium, Cephapirin, Cephradine), Ciprofloxacin (Enrofloxacin), Clarithromycin, Clavulanic acid (Amoxicillin-clavulanic acid), Clindamycin, Colicin, Cyclosporin (e.g., Cyclosporin A), Dalfopristin/quinupristin, Daunorubicin,

Doxorubicin, Epirubicin, GSK 1322322, Geneticin, Gentamicin, Gentamicin sulfate,

Gramicidin (e.g., Gramicidin A), Grepafloxacin hydrochloride, Ivermectin, Kanamycin (e.g., Kanamycin A), Lasalocid, Leucomycin, Levofloxacin, Linezolid, Lomefloxacin, Lovastatin, MK 7655, Meropenem, Mevastatin, Mithramycin, Mitomycin, Monomycin, Natamycin, Neocarzinostatin, Neomycin (e.g., Neomycin sulfate), Nystatin, Oligomycin, Olivomycin, Pefloxacin, Penicillin (e.g., 6-Aminopenicillanic acid, Amoxicillin (e.g., Amoxicillin- clavulanic acid), Ampicillin, Ampicillin sodium, Azlocillin, Carbenicillin, Cefoxitin, Cephaloridine, Cloxacillin, Dicloxacillin, Mecillinam, Methicillin, Mezlocillin, Nafcillin, Oxacillin, Penicillin G, Penicillin G potassium, Penicillin G procaine, Penicillin G sodium, Penicillin V, Piperacillin, Piperacillin-tazobactam, Sulbactam, Tazobactam, Ticarcillin), Phleomycin, Polymyxin (e.g., Colistin, Polymyxin B), Pyocin (e.g., Pyocin R), RPX 7009, Rapamycin, Ristocetin, Salinomycin, Sparfloxacin, Spectinomycin, Spiramycin, Streptogramin, Streptovaricin, Tedizolid phosphate, Teicoplanin, Telithromycin, Tetracyclines (e.g., Achromycin V, Demeclocycline, Doxycycline, Doxycycline

monohydrate, Minocycline, Oxytetracycline, Oxytetracycline hydrochloride Tetracycline, Tetracycline hydrochloride), Trichostatin A, Trovafloxacin, Tunicamycin, Tyrocidine, Valinomycin.

[00443] Pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. In general, such preparatory methods include the steps of bringing the compound of the present invention (the“active ingredient”) into association with a carrier or excipient, and/or one or more other accessory ingredients, and then, if necessary and/or desirable, shaping, and/or packaging the product into a desired single- or multi-dose unit.

[00444] Pharmaceutical compositions can be prepared, packaged, and/or sold in bulk, as a single unit dose, and/or as a plurality of single unit doses. A“unit dose” is a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and/or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage.

[00445] Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition of the invention will vary, depending upon the identity, size, and/or condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100% (w/w) active ingredient.

[00446] Pharmaceutically acceptable excipients used in the manufacture of provided pharmaceutical compositions include inert diluents, dispersing and/or granulating agents, surface active agents and/or emulsifiers, disintegrating agents, binding agents, preservatives, buffering agents, lubricating agents, and/or oils. Excipients such as cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, and perfuming agents may also be present in the composition.

[00447] Exemplary diluents include calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate lactose, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, cornstarch, powdered sugar, and mixtures thereof.

[00448] Exemplary granulating and/or dispersing agents include potato starch, corn starch, tapioca starch, sodium starch glycolate, clays, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose, and wood products, natural sponge, cation-exchange resins, calcium carbonate, silicates, sodium carbonate, cross-linked poly(vinyl-pyrrolidone) (crospovidone), sodium carboxymethyl starch (sodium starch glycolate), carboxymethyl cellulose, cross- linked sodium carboxymethyl cellulose (croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate (Veegum), sodium lauryl sulfate, quaternary ammonium compounds, and mixtures thereof.

[00449] Exemplary surface active agents and/or emulsifiers include natural emulsifiers (e.g., acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin), colloidal clays (e.g., bentonite (aluminum silicate) and Veegum (magnesium aluminum silicate)), long chain amino acid derivatives, high molecular weight alcohols (e.g., stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g., carboxy polymethylene, polyacrylic acid, acrylic acid polymer, and carboxyvinyl polymer), carrageenan, cellulosic derivatives (e.g., carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g., polyoxyethylene sorbitan monolaurate (Tween 20),

polyoxyethylene sorbitan (Tween 60), polyoxyethylene sorbitan monooleate (Tween 80), sorbitan monopalmitate (Span 40), sorbitan monostearate (Span 60), sorbitan tristearate (Span 65), glyceryl monooleate, sorbitan monooleate (Span 80)), polyoxyethylene esters (e.g., polyoxyethylene monostearate (Myrj 45), polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and Solutol), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g., Cremophor™), polyoxyethylene ethers, (e.g., polyoxyethylene lauryl ether (Brij 30)), poly(vinyl-pyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, Pluronic F-68, Poloxamer188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, and/or mixtures thereof.

[00450] Exemplary binding agents include starch (e.g., cornstarch and starch paste), gelatin, sugars (e.g., sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol, etc.), natural and synthetic gums (e.g., acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl

methylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl-pyrrolidone), magnesium aluminum silicate (Veegum), and larch arabogalactan), alginates, polyethylene oxide, polyethylene glycol, inorganic calcium salts, silicic acid, polymethacrylates, waxes, water, alcohol, and/or mixtures thereof.

[00451] Exemplary preservatives include antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, alcohol preservatives, acidic preservatives, and other preservatives.

[00452] Exemplary antioxidants include alpha tocopherol, ascorbic acid, acorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, and sodium sulfite.

[00453] Exemplary chelating agents include ethylenediaminetetraacetic acid (EDTA) and salts and hydrates thereof (e.g., sodium edetate, disodium edetate, trisodium edetate, calcium disodium edetate, dipotassium edetate, and the like), citric acid and salts and hydrates thereof (e.g., citric acid monohydrate), fumaric acid and salts and hydrates thereof, malic acid and salts and hydrates thereof, phosphoric acid and salts and hydrates thereof, and tartaric acid and salts and hydrates thereof. Exemplary antimicrobial preservatives include benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and thimerosal.

[00454] Exemplary antifungal preservatives include butyl paraben, methyl paraben, ethyl paraben, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and sorbic acid.

[00455] Exemplary alcohol preservatives include ethanol, polyethylene glycol, phenol, phenolic compounds, bisphenol, chlorobutanol, hydroxybenzoate, and phenylethyl alcohol.

[00456] Exemplary acidic preservatives include vitamin A, vitamin C, vitamin E, beta- carotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and phytic acid.

[00457] Other preservatives include tocopherol, tocopherol acetate, deteroxime mesylate, cetrimide, butylated hydroxyanisol (BHA), butylated hydroxytoluened (BHT),

ethylenediamine, sodium lauryl sulfate (SLS), sodium lauryl ether sulfate (SLES), sodium bisulfite, sodium metabisulfite, potassium sulfite, potassium metabisulfite, Glydant Plus, Phenonip, methylparaben, Germall 115, Germaben II, Neolone, Kathon, and Euxyl. In certain embodiments, the preservative is an anti-oxidant. In other embodiments, the preservative is a chelating agent.

[00458] Exemplary buffering agents include citrate buffer solutions, acetate buffer solutions, phosphate buffer solutions, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium glubionate, calcium gluceptate, calcium gluconate, D- gluconic acid, calcium glycerophosphate, calcium lactate, propanoic acid, calcium levulinate, pentanoic acid, dibasic calcium phosphate, phosphoric acid, tribasic calcium phosphate, calcium hydroxide phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixtures, dibasic potassium phosphate, monobasic potassium phosphate, potassium phosphate mixtures, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, dibasic sodium phosphate, monobasic sodium phosphate, sodium phosphate mixtures, tromethamine, magnesium hydroxide, aluminum hydroxide, alginic acid, pyrogen-free water, isotonic saline, Ringer’s solution, ethyl alcohol, and mixtures thereof.

[00459] Exemplary lubricating agents include magnesium stearate, calcium stearate, stearic acid, silica, talc, malt, glyceryl behanate, hydrogenated vegetable oils, polyethylene glycol, sodium benzoate, sodium acetate, sodium chloride, leucine, magnesium lauryl sulfate, sodium lauryl sulfate, and mixtures thereof.

[00460] Exemplary natural oils include almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, camomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macademia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils. Exemplary synthetic oils include, but are not limited to, butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, and mixtures thereof.

[00461] Liquid dosage forms for oral and parenteral administration include

pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredients, the liquid dosage forms may comprise inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (e.g., cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. In certain embodiments for parenteral administration, the conjugates of the invention are mixed with solubilizing agents such as Cremophor™, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and mixtures thereof.

[00462] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions can be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer’s solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or di-glycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables.

[00463] The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.

[00464] In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle.

[00465] Compositions for rectal or vaginal administration are typically suppositories which can be prepared by mixing the conjugates of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active ingredient. [00466] While it may be possible for the compounds disclosed herein, or pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, hydrates, or polymorphs thereof, to be administered orally as they are, it is also possible to present them as a pharmaceutical formulation or dosage. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active ingredient is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or (a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, (c) humectants such as glycerol, (d) disintegrating agents such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, (e) solution retarding agents such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, (h) absorbents such as kaolin and bentonite clay, and (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may comprise buffering agents.

[00467] Solid compositions of a similar type can be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Solid compositions of a similar type can be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene glycols and the like.

[00468] The active ingredient can be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active ingredient can be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may comprise buffering agents. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner.

Examples of embedding compositions which can be used include polymeric substances and waxes.

[00469] Dosage forms for topical and/or transdermal administration of a compound of this invention may include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants and/or patches. Generally, the active ingredient is admixed under sterile conditions with a pharmaceutically acceptable carrier or excipient and/or any needed preservatives and/or buffers as can be required. Additionally, the present invention contemplates the use of transdermal patches, which often have the added advantage of providing controlled delivery of an active ingredient to the body. Such dosage forms can be prepared, for example, by dissolving and/or dispensing the active ingredient in the proper medium. Alternatively or additionally, the rate can be controlled by either providing a rate controlling membrane and/or by dispersing the active ingredient in a polymer matrix and/or gel.

[00470] Suitable devices for use in delivering intradermal pharmaceutical compositions described herein include short needle devices. Intradermal compositions can be administered by devices which limit the effective penetration length of a needle into the skin. Ballistic powder/particle delivery devices which use compressed gas to accelerate vaccine in powder form through the outer layers of the skin to the dermis are suitable. Alternatively or additionally, conventional syringes can be used in the classical mantoux method of intradermal administration.

[00471] Formulations suitable for topical administration include, but are not limited to, liquid and/or semi-liquid preparations such as liniments, lotions, oil in water and/or water in oil emulsions such as creams, ointments and/or pastes, and/or solutions and/or suspensions. Topically-administrable formulations may, for example, comprise from about 1% to about 10% (w/w) active ingredient, although the concentration of the active ingredient can be as high as the solubility limit of the active ingredient in the solvent. Formulations for topical administration may further comprise one or more of the additional ingredients described herein.

[00472] Low boiling propellants generally include liquid propellants having a boiling point of below 65 °F at atmospheric pressure. Generally the propellant may constitute 50 to 99.9% (w/w) of the composition, and the active ingredient may constitute 0.1 to 20% (w/w) of the composition. The propellant may further comprise additional ingredients such as a liquid non-ionic and/or solid anionic surfactant and/or a solid diluent (which may have a particle size of the same order as particles comprising the active ingredient).

[00473] Pharmaceutical compositions of the invention formulated for pulmonary delivery may provide the active ingredient in the form of droplets of a solution and/or suspension. Such formulations can be prepared, packaged, and/or sold as aqueous and/or dilute alcoholic solutions and/or suspensions, optionally sterile, comprising the active ingredient, and may conveniently be administered using any nebulization and/or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface active agent, and/or a preservative such as methylhydroxybenzoate. The droplets provided by this route of administration may have an average diameter in the range from about 0.1 to about 200 nanometers.

[00474] Formulations described herein as being useful for pulmonary delivery are useful for intranasal delivery of a pharmaceutical composition of the invention. Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle from about 0.2 to 500 micrometers. Such a formulation is administered by rapid inhalation through the nasal passage from a container of the powder held close to the nares.

[00475] Formulations for nasal administration may, for example, comprise from about as little as 0.1% (w/w) and as much as 100% (w/w) of the active ingredient, and may comprise one or more of the additional ingredients described herein. A pharmaceutical composition of the invention can be prepared, packaged, and/or sold in a formulation for buccal

administration. Such formulations may, for example, be in the form of tablets and/or lozenges made using conventional methods, and may contain, for example, 0.1 to 20% (w/w) active ingredient, the balance comprising an orally dissolvable and/or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations for buccal administration may comprise a powder and/or an aerosolized and/or atomized solution and/or suspension comprising the active ingredient. Such powdered, aerosolized, and/or aerosolized formulations, when dispersed, may have an average particle and/or droplet size in the range from about 0.1 to about 200 nanometers, and may further comprise one or more of the additional ingredients described herein.

[00476] A pharmaceutical composition of the invention can be prepared, packaged, and/or sold in a formulation for ophthalmic administration. Such formulations may, for example, be in the form of eye drops including, for example, a 0.1-1.0% (w/w) solution and/or suspension of the active ingredient in an aqueous or oily liquid carrier or excipient. Such drops may further comprise buffering agents, salts, and/or one or more other of the additional ingredients described herein. Other opthalmically-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form and/or in a liposomal preparation. Ear drops and/or eye drops are contemplated as being within the scope of this invention.

[00477] Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. Modification of pharmaceutical

compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and/or perform such modification with ordinary experimentation.

[00478] Compounds provided herein are typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject or organism will depend upon a variety of factors including the disease being treated and the severity of the disorder; the activity of the specific active ingredient employed; the specific composition employed; the age, body weight, general health, sex, and diet of the subject; the time of administration, route of administration, and rate of excretion of the specific active ingredient employed; the duration of the treatment; drugs used in combination or coincidental with the specific active ingredient employed; and like factors well known in the medical arts.

[00479] The compounds and compositions provided herein can be administered by any route, including enteral (e.g., oral), parenteral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical (as by powders, ointments, creams, and/or drops), mucosal, nasal, bucal, sublingual; by intratracheal instillation, bronchial instillation, and/or inhalation; and/or as an oral spray, nasal spray, and/or aerosol. Specifically contemplated routes are oral administration, intravenous administration (e.g., systemic intravenous injection), regional administration via blood and/or lymph supply, and/or direct administration to an affected site. The inventive compounds and compositions may also be mixed with blood ex vivo, and the resulting mixture may be administered (e.g., intravenously) to a subject. In general the most appropriate route of administration will depend upon a variety of factors including the nature of the agent (e.g., its stability in the environment of the gastrointestinal tract), and/or the condition of the subject (e.g., whether the subject is able to tolerate oral administration).

[00480] The exact amount of a compound required to achieve an effective amount will vary from subject to subject, depending, for example, on species, age, and general condition of a subject, severity of the side effects or disorder, identity of the particular compound, mode of administration, and the like. An effective amount may be included in a single dose (e.g., single oral dose) or multiple doses (e.g., multiple oral doses). In certain embodiments, when multiple doses are administered to a subject or applied to a tissue or cell, any two doses of the multiple doses include different or substantially the same amounts of a compound described herein. In certain embodiments, when multiple doses are administered to a subject or applied to a tissue or cell, the frequency of administering the multiple doses to the subject or applying the multiple doses to the tissue or cell is three doses a day, two doses a day, one dose a day, one dose every other day, one dose every third day, one dose every week, one dose every two weeks, one dose every three weeks, or one dose every four weeks. In certain embodiments, the frequency of administering the multiple doses to the subject or applying the multiple doses to the tissue or cell is one dose per day. In certain embodiments, the frequency of administering the multiple doses to the subject or applying the multiple doses to the tissue or cell is two doses per day. In certain embodiments, the frequency of

administering the multiple doses to the subject or applying the multiple doses to the tissue or cell is three doses per day. In certain embodiments, when multiple doses are administered to a subject or applied to a tissue or cell, the duration between the first dose and last dose of the multiple doses is one day, two days, four days, one week, two weeks, three weeks, one month, two months, three months, four months, six months, nine months, one year, two years, three years, four years, five years, seven years, ten years, fifteen years, twenty years, or the lifetime of the subject, tissue, or cell. In certain embodiments, the duration between the first dose and last dose of the multiple doses is three months, six months, or one year. In certain embodiments, the duration between the first dose and last dose of the multiple doses is the lifetime of the subject, tissue, or cell. In certain embodiments, a dose (e.g., a single dose, or any dose of multiple doses) described herein includes independently between 0.1 µg and 1 µg, between 0.001 mg and 0.01 mg, between 0.01 mg and 0.1 mg, between 0.1 mg and 1 mg, between 1 mg and 3 mg, between 3 mg and 10 mg, between 10 mg and 30 mg, between 30 mg and 100 mg, between 100 mg and 300 mg, between 300 mg and 1,000 mg, or between 1 g and 10 g, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 1 mg and 3 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 3 mg and 10 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 10 mg and 30 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 30 mg and 100 mg, inclusive, of a compound described herein.

[00481] It will be appreciated that dose ranges as described herein provide guidance for the administration of provided pharmaceutical compositions to an adult. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult.

[00482] It will be also appreciated that a compound or composition, as described herein, can be administered in combination with one or more additional therapeutically active agents. The compounds or compositions can be administered in combination with additional therapeutically active agents that improve their bioavailability, reduce and/or modify their metabolism, inhibit their excretion, and/or modify their distribution within the body. It will also be appreciated that the therapy employed may achieve a desired effect for the same disorder, and/or it may achieve different effects.

[00483] The compound or composition can be administered concurrently with, prior to, or subsequent to, one or more additional therapeutically active agents. In general, each agent will be administered at a dose and/or on a time schedule determined for that agent. In will further be appreciated that the additional therapeutically active agent utilized in this combination can be administered together in a single composition or administered separately in different compositions. The particular combination to employ in a regimen will take into account compatibility of the inventive compound with the additional therapeutically active agent and/or the desired therapeutic effect to be achieved. In general, it is expected that additional therapeutically active agents in combination be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually. [00484] Exemplary additional therapeutically active agents include, but are not limited to, anti-cancer agents, anti-diabetic agents, anti-inflammatory agents, immunosuppressant agents, and a pain-relieving agent. Therapeutically active agents include small organic molecules such as drug compounds (e.g., compounds approved by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells.

[00485] Also encompassed by the invention are kits (e.g., pharmaceutical packs). The kits provided may comprise a composition or compound as described herein and a container (e.g., a vial, ampule, bottle, syringe, and/or dispenser package, or other suitable container). The kits provided may comprise a pharmaceutical composition or compound and a container (e.g., a vial, ampule, bottle, syringe, and/or dispenser package, or other suitable container). In some embodiments, provided kits may optionally further include a second container comprising a pharmaceutical excipient for dilution or suspension of the pharmaceutical composition or compound as described herein. In some embodiments, the inventive pharmaceutical composition or compound provided in the first container and the second container are combined to form one unit dosage form.

[00486] In another aspect, the invention provides a kit comprising a compound of any one of Formulae (I-A)-(III-A), or a salt, tautomer, stereoisomer, solvate, hydrate, or a polymorph thereof, and optionally a carrier to treat or prevent an infectious disease and/or biofilm formation in a subject.

[00487] In yet another aspect, the invention provides a kit comprising a compound capable of chelating a metal, or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or a polymorph thereof, and optionally a pharmaceutically acceptable carrier for treating and/or preventing an infectious disease. In yet another aspect, the invention provides a kit comprising a compound capable of chelating a metal, or a salt, tautomer, stereoisomer, solvate, hydrate, or a polymorph thereof, and optionally a carrier for treating and/or preventing formation of biofilms. In certain embodiments, the kit is to treat or prevent biofilm formation in a subject. In certain embodiments, the kit is to treat or prevent biofilm formation on an object. In certain embodiments, the kit is to treat or prevent biofilm formation on a surface. In certain embodiments, the kit further comprises an antimicrobial agent (e.g., antibiotics). In certain embodiments, the inventive kits include a first container containing a therapeutically effective amount of a compound capable of chelating a metal (e.g., a compound of any one of Formulae (I-A)-(III-A)), or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof; and instructions for administering the compound to the subject to treat and/or prevent an infectious disease and/or biofilm formation in a subject. In certain embodiments, the inventive kits include a first container containing a therapeutically effective amount of a compound capable of chelating a metal (e.g., a compound of any one of Formulae (I-A)-(III-A)), or a pharmaceutically acceptable salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof; and an antimicrobial agent; and a second container containing instructions for administering the compound to the subject to treat and/or prevent an infectious disease and/or biofilm formation. In certain embodiments, the inventive kits include a first container containing a therapeutically effective amount of a compound capable of chelating a metal (e.g., a compound of any one of Formulae (I-A)-(III-A)), or a salt, tautomer, stereoisomer, solvate, hydrate, or polymorph thereof; and instructions for applying the compound to an object to treat and/or prevent biofilm formation. In certain embodiments, the kit is a cleaning kit. In certain embodiments, the kit further comprises a disinfectant. A kit may also include multiple unit dosages, for example, for multiple days of treatment. In certain embodiments, the instruction includes a notice in the form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceutical products, which notice reflects approval by the agency of manufacture, use, or sale for human administration. E ^{QUIVALENTS AND} S ^COPE

[00488] In the claims articles such as“a,”“an,” and“the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include“or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

[00489] Furthermore, the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the invention, or aspects of the invention, is/are referred to as comprising particular elements and/or features, certain embodiments of the invention or aspects of the invention consist, or consist essentially of, such elements and/or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein. It is also noted that the terms“comprising” and“containing” are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub–range within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[00490] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the invention can be excluded from any claim, for any reason, whether or not related to the existence of prior art.

[00491] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present invention, as defined in the following claims.