Compositions containing polymeric conjugates of chelators and method of use thereof

Abstract

Provided herein are compounds that bind metal ions (e.g., free metal ions or metal ions bound to low affinity ligands) in a sample or subject. Also provided herein are methods of using the compounds for chelating metal ions and for the treatment of diseases associated with abnormal levels of metal ions. Methods of preparing the compounds and pharmaceutical compositions are also provided.

Description

[0001] Attorney Docket No.125141.04766.MGH2022-378 COMPOSITIONS CONTAINING POLYMERIC CONJUGATES OF CHELATORS AND METHOD OF USE THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority from U.S. Provisional Patent Application Serial No.63 / 660,292, filed June 14, 2024, the contents of which are incorporated herein by reference. FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with Government support under Grant No. NHLBI #R01- HL143020, awarded by the National Institutes of Health. The US Government has certain rights in the invention. TECHNICAL FIELD Provided herein are compositions containing polymeric conjugates of chelators. Also provided are methods of using the compositions for treating diseases. BACKGROUND Certain metals are essential elements for biological system, but high concentration of certain metals is toxic. For example, iron is an essential metal nutrient for various biological processes. However, excess iron can lead to severe health complications, including heart failure, liver cirrhosis, cancer, arthritis, dyslipidemia, diabetes, gonadal dysfunction, and neurodegenerative diseases. Iron overload disorders, such as hereditary hemochromatosis and secondary iron overload due to repetitive blood transfusions, affect millions of individuals globally. Iron chelation therapy using small molecules is widely used to manage iron overload disorders. Nevertheless, FDA-approved iron chelators, including deferoxamine (DFO), deferiprone, and deferasirox, suffer from unfavorable pharmacokinetics (PK) and pharmacodynamics (PD), nonspecific tissue distribution, and significant adverse effects. In particular, DFO exhibit extremely short half-lives (5-15 min in rodents) and inefficient distribution within the body including the kidney, muscle, brain, and lungs, requiring frequent Attorney Docket No.125141.04766.MGH2022-378 dosing and potentially impacting patient compliance. The nonspecific distribution of DFO induces severe adverse effects, such as nephrotoxicity, anaphylaxis, and gastrointestinal disturbances, limiting their long-term use. Thus, there remains a need for alternative approaches for metal chelation therapy with desirable pharmacokinetic properties, more specific tissue distribution, and reduced adverse effects. SUMMARY The present application provides a compound of Formula I: (A)a—B Formula (I) or a pharmaceutically acceptable salt thereof, wherein: A is a labeling group or a group comprising a zwitterion; B is a biocompatible polymer substituted by one or more C groups and one or more – (D)d-E groups; each C is independently selected from the group consisting of H, OH, -(X1)m-C(=Y1)- (X2)n-R1, wherein, X1, X2 and Y1 are independently N, O, or S; R1is selected from or H, OH, NR2R3, SH, substituted or unsubstituted C1-6alkyl, C1-6heteroalkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, aryl, heteroaryl, C1-6alkoxy, aryloxy, or C1-6heteroalkoxy ; each D is an independently selected linking group; each E is an independently selected C or a metal chelating group; and a, d, m and n is 0 or 1, wherein at least one E is a metal chelating group. In some embodiment, the composition of Formula I contains at least one metal chelating group. In some embodiments, A comprises a radioisotope labelled group, chromogenic group, fluorescent group, or one or more cationic groups each independently selected from the group consisting of ammonium, C1-6 alkylammonium, di(C1-6 alkyl)ammonium, tri(C1-6 Attorney Docket No.125141.04766.MGH2022-378 alkyl)ammonium, a cationic 5-10 membered heteroaryl group, and a cationic 4-10 membered heterocycloalkyl group, wherein the cationic 5-10 membered heteroaryl group and cationic 4-10 membered heterocycloalkyl group are each optionally substituted by 1, 2, 3, or 4 independently selected C1-6 alkyl groups. In some embodiments, A comprises one or more cationic groups which are each independently selected from the group consisting of tri(C1-6 alkyl)ammonium and a cationic 5-10 membered heteroaryl group which is optionally substituted by 1, 2, 3, or 4 independently selected C1-6alkyl groups. In some embodiments, A comprises one or more cationic groups which are each independently selected from the group consisting of trimethylammonium and N-(C1-6alkyl)indolium, wherein the N-(C1-6alkyl)indolium is optionally substituted by 1 or 2 independently selected C1-6alkyl groups. In some embodiments, A comprises one or more anionic groups each independently selected from the group consisting of oxide, carbonate, carboxylate, phosphate, sulfide, sulfinate, and sulfonate. In some embodiments, A comprises one or more anionic groups which are each sulfonate. In some embodiments, A is selected from the group consisting of formulas A-1 and A-2: O RA indicates the bond between A and B; X is selected from the group consisting of a bond, C, CH2, NH, O, Se, and S; each RAis an independently selected anionic group; each RCis an independently selected cationic group; and L1, L2, and L3are each an independently selected C1-6 alkylene group. In some embodiments, each RCis independently selected from the group consisting of ammonium, C1-6alkylammonium, di(C1-6alkyl)ammonium, and tri(C1-6alkyl)ammonium. In Attorney Docket No.125141.04766.MGH2022-378 some embodiments, each RCis an independently selected tri(C1-6 alkyl)ammonium group. In some embodiments, each RCis trimethylammonium. In some embodiments, each RAis independently selected from the group consisting of oxide, carbonate, carboxylate, phosphate, sulfide, sulfinate, and sulfonate. In some embodiments, each RAis sulfonate. In some embodiments, L1is propylene. In some embodiments, L2is propylene. In some embodiments, L3is ethylene. In some embodiments, X is a bond. In some embodiments, X is CH2. In some embodiments, A is: . In some with significant potential to mitigate the side effects associated with conventional iron chelation therapies for patients with iron overload disorders, thereby enhancing therapeutic efficacy and improving pharmacokinetic profiles. A type of renal-clearable nanochelator, referred to as ZW-DFO-EPL- was previous reported, wherein ZW is a group containing zwitterion. These nanochelators, constructed on an FDA-approved natural food preservative epsilon-poly-l-lysine (EPL) backbone, bind and eliminate excess iron solely through urinary excretion, evading the immune system and nonspecific tissue distribution. In preclinical models, these nanochelators demonstrated improved PK and biodistribution profiles, offering enhanced efficacy and safety compared to existing iron chelators. However, the lab-scale synthesis using unoptimized chemical procedures posed a challenge for clinical translation. Moreover, the relatively short blood half-life and suboptimal PK of ZW-DFO-EPL- were impediments to advancing to first-in- Attorney Docket No.125141.04766.MGH2022-378 human clinical trials. Thus, there is a need for alternative nanochelators and improved synthesis scheme to for scale-up preparation of these nanochelators. In some embodiments, B is selected from the group consisting of a biocompatible polymer selected from a group consisting of polyalkylene oxide, such as polyethylene glycol, polypropylene glycol, a biocompatible polypeptide and a biocompatible polyester, or a copolymer thereof, wherein each of which is substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, B is selected from the group consisting of polylysine, polylactic acid, poly(lactic-co-glycolic acid), polyaspartic acid, polyglutamic acid, polycaprolactone, polyglycolide, poly(ethylene glycol), and a copolymer thereof, each of which is substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, B is polylysine substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, the polylysine is ε-poly-L-lysine substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, B is: wherein: indicates the bond between B and A; indicates the monomeric units containing C or E are randomly connected; s is an integer from 5 to 50; and t is an integer from 1 to 10. In some embodiments, molecular weight of B is 1,000-100,000 or B has a hydrodynamic radius of from about 1 nm to about 10 nm. Attorney Docket No.125141.04766.MGH2022-378 In some embodiments, each C is independently selected from the group consisting of hydrogen and an anionic group comprising one or more alkylene groups, one or more carbonyl groups, or one or more carboxyl groups, or any combination thereof. In some embodiments, C is an anionic group of the following formula: O O R11wherein: indicates the bond between C and B; R11 and R12 are independently selected from H, OH, substituted or unsubstituted C1-6 alkyl, C1-6heteroalkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, aryl, heteroaryl, C1-6alkoxy, aryloxy, or C1-6 heteroalkoxy; and p is an integer from 1 to 10. In some embodiments, p is an integer from 1 to 5. In some embodiments, D is a linking group having at least two functional moieties to form a linkage with either B and E and comprising one or more alkylene groups, one or more carbonyl groups, or one or more carboxyl groups, or any combination thereof. In some embodiments, D is a linking group of the following formula: O O E wherein: indicates the bond between D and B; indicates the bond between D and E; R13 and R14 are independently selected from H, OH, substituted or unsubstituted C1-6 alkyl, C1-6heteroalkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, aryl, heteroaryl, C1-6alkoxy, aryloxy, or C1-6 heteroalkoxy and Attorney Docket No.125141.04766.MGH2022-378 q is an integer from 1-20, 2-15, 3-15, 3-12, 3-10 or 5-10. In some embodiments, q is an integer from 1 to 5. In some embodiments, E is a metal chelating moiety selected from the group consisting of an iron chelating group, a lead chelating group, a copper chelating group, an arsenic chelating group, a mercury chelating group, and a manganese chelating group. In some embodiments, E is an iron chelating group. In some embodiments, E is selected from the group consisting of dimercaptosuccinic acid, dimercaprol, ethylenediaminetetraacetic acid, p-aminosalicyclic acid, D-penicillamine, deferoxamine, deferiprone, and deferasirox. In some embodiments, E is deferoxamine or its derivatives. In some embodiments, B is polylysine and E is an iron chelating group, wherein the polylysine is substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, the polylysine is ε-poly-L-lysine (i.e., EPL) substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, B is ε-poly-L-lysine and E is deferoxamine (i.e., DFO), wherein the ε-poly-L-lysine is substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, the molar ratio (i.e., stoichiometry) of the metal chelating agent E (e.g., an iron chelating agent) to the biocompatible polymer B in the compounds of Formula I is from about 20:1 to about 1:1, for example, about 20:1 to about 2:1, about 20:1 to about 4:1, about 20:1 to about 6:1, about 20:1 to about 8:1, about 10:1 to about 1:1, about 10:1 to about 2:1, about 10:1 to about 4:1, about 10:1 to about 6:1, about 8:1 to about 1:1, about 8:1 to about 2:1, about 8:1 to about 4:1, about 6:1 to about 1:1, about 6:1 to about 2:1, or about 4:1 to about 1:1. In some embodiments, the molar ratio (i.e., stoichiometry) of the metal chelating agent E (e.g., an iron chelating agent) to the biocompatible polymer B in the compounds of Formula I is about 4:1, about 6:1, about 8:1, or about 10:1. In some embodiments: A is selected from the group consisting of formulas A-1 and A-2: Attorney Docket No.125141.04766.MGH2022-378 O L3O RA indicates the bond between A and B; each RAis an independently selected anionic group; each RCis an independently selected cationic group; and L1, L2, and L3are each an independently selected C1-6 alkylene group; B is selected from the group consisting of a biocompatible polypeptide and a biocompatible polyester, each of which is substituted by one or more C groups and one or more - (D)d-E groups; C is an anionic group of the following formula: O O wherein: indicates the bond between C and B; p is an integer from 1 to 10; D is a linking group of the following formula: O O E wherein: Attorney Docket No.125141.04766.MGH2022-378 indicates the bond between D and B; indicates the bond between D and E; and q is an integer from 1 to 20 or 1 to 10; and E is a metal chelating group. In some embodiments: A is a group of the following formula: wherein: indicates the bond between A and B; each RAis independently selected from the group consisting of oxide, carbonate, carboxylate, phosphate, sulfide, sulfinate, and sulfonate; each RCis independently selected from the group consisting of ammonium, C1-6alkylammonium, di(C1-6alkyl)ammonium, and tri(C1-6alkyl)ammonium; and L1, L2, and L3are each an independently selected C1-6 alkylene group; B is selected from the group consisting of polylysine, polylactic acid, and poly(lactic-co- glycolic acid), polyaspartic acid, polyglutamic acid, polycaprolactone, polyglycolide, poly(ethylene glycol), and a copolymer thereof, each of which are substituted by one or more C groups and one or more -(D)d-E groups; C is an anionic group of the following formula: O O R6BpO R5 Attorney Docket No.125141.04766.MGH2022-378 wherein: indicates the bond between C and B; p is an integer from 1 to 10; D is a linking group of the following formula: O O R6Ewherein: indicates the bond between D and B; indicates the bond between D and E; and q is an integer from 1 to 10; and E is a metal chelating group. In some embodiments: A is a group of the following formula: wherein: indicates the bond between A and B; each RAis sulfonate; each RCis tri(C1-6alkyl)ammonium; and L1, L2, and L3are each an independently selected C1-6 alkylene group; Attorney Docket No.125141.04766.MGH2022-378 B is polylysine which is substituted by one or more C groups and one or more -(D)d-E groups; C is an anionic group of the following formula: wherein: indicates the bond between C and B; p is an integer from 1 to 5; D is a linking group of the following formula: O O R6Ewherein: indicates the bond between D and B; indicates the bond between D and E; and q is an integer from 1 to 5; and E is a metal chelating group. In some embodiments, E is selected from the group consisting of an iron chelating group, a lead chelating group, and a copper chelating group. In some embodiments, E is an iron chelating group. In some embodiments, E is selected from the group consisting of dimercaptosuccinic acid, dimercaprol, ethylenediaminetetraacetic acid, P-aminosalicyclic acid, D-penicillamine, deferoxamine, deferiprone, and deferasirox. In some embodiments, E is deferoxamine. The present application further provides a pharmaceutical composition comprising the compound provided herein (e.g., a compound of Formula I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Attorney Docket No.125141.04766.MGH2022-378 The present application further provides a method of treating a disease or a disorder associated with an abnormal amount of free metal ions in a subject comprising: administering a therapeutically effective amount of a composition comprising a compound as described herein to a subject in need thereof. In some embodiments, the disease or disorder is thalassemia, myelodysplastic syndrome, sickle cell anemia, Blackfan Diamond anemia, rheumatoid arthritis, hemolysis, chronic iron overload due to transfusion-dependent anemias, acute kidney injury, traumatic brain injury, Alzheimer's disease, or a combination thereof. The acute kidney injury includes prerenal, intrarenal (intrinsic) or postrenal and is caused by, not limited to, Rhabdomyolysis, ischemia, cardiac surgery, nephrotoxic substance, acute tubular necrosis (ATN), glomerular damage, or any other damage or injury to kidney tissue itself. The method of treatment includes post injury treatment or preventive treatment such as presurgical treatment before the cardiac surgery, where the damage to kidney tissue or elevated level of metal, especially iron, ion is known or potentially known. The present application further provides a method of chelating a metal ion in a cell or tissue sample, comprising contacting the cell sample or tissue sample with a compound provided herein (e.g., a compound of Formula I), or a pharmaceutically acceptable salt thereof. The present application further provides a method of reducing the amount of free metal ions in a cell or tissue sample, comprising contacting the cell or tissue sample with a compound provided herein (e.g., a compound of Formula I), or a pharmaceutically acceptable salt thereof. The present application further provides a method of chelating metal ions in a subject, comprising administering to the subject a therapeutically effective amount of a compound provided herein (e.g., a compound of Formula I), or a pharmaceutically acceptable salt thereof. The present application further provides a method of reducing the amount of free metal ions in a subject, comprising administering to the subject a compound provided herein (e.g., a compound of Formula I), or a pharmaceutically acceptable salt thereof. The present application further provides a method of reducing the amount of free metal ions in a subject, comprising: i) diagnosing the subject as having an abnormal level of free metal ions; and Attorney Docket No.125141.04766.MGH2022-378 ii) administering to the subject a therapeutically effective amount of a compound provided herein (e.g., a compound of Formula I), or a pharmaceutically acceptable salt thereof. The present application further provides a method of reducing the amount of free metal ions in a subject, comprising administering to a subject determined to have an abnormal level of free metal ions a therapeutically effective amount of a compound provided herein (e.g., a compound of Formula I), or a pharmaceutically acceptable salt thereof. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. BRIEF DESCRIPTION OF DRAWINGS The foregoing features of embodiments will be more readily understood by reference to the following detailed description, taken with reference to the accompanying drawings, in which: FIG.1A is a schematic of a nanochelator according to one example of the present disclosure. Specifically, an improved chemical procedure for large-scale synthesis of ZW-DFO- EPL is provided. FIG.1B is a schematic of a nanochelator according to one example of the present disclosure. Specifically, a conventional and clinically optimize reaction chemistry for DFO-EPL- is provided. FIG.2 is a photograph (left) and two charts of amine conversion for a ninhydrin test for blank, ZW-EPL+, ZW-EPL- (middle), EPL+, and EPL- (right). FIG.3A is a UV-VIS spectroscopy chart at 430 nm (top) and iron chelation titration chart (bottom) of ZW-DFO4-EPL-. FIG.3B is a UV-VIS spectroscopy chart at 430 nm (top) and iron chelation titration chart (bottom) of ZW-DFO6-EPL-. FIG.3C is a UV-VIS spectroscopy chart at 430 nm (top) and iron chelation titration chart (bottom) of ZW-DFO8-EPL-. Attorney Docket No.125141.04766.MGH2022-378 FIG.4 is a synthesis scheme of ZW-DFO-EPL- prepared by using excess DMTMM and DFO. FIG.5A is a table (left) and a plot of DFO equivalence to conjugation ratio (right) for optimization of DFO conjugation using EDC / NHS chemistry. The number of DFO labeling ratio on EPL was assessed by 1H-NMR. Data points in graph are presented in duplicate with the exception of (*) which is a single data point, standard error bars displayed. FIG.5B is a table (left) and a plot of DFO equivalence to conjugation ratio (right) for optimization of DFO conjugation using EDC / NHS chemistry. The number of DFO labeling ratio on EPL was assessed by 1H-NMR. FIG.6A is a MALDI-TOF mass spectrum of of EPL-. FIG.6B shows SEC-HPLC analyses of EPL-. FIG.6C shows SEC-HPLC of hydrodynamic diameter (HD) standards. FIG. 6D is a schematic for potential cross-linking between the hydroxamic acid of DFO and the carbonyl carbon NHS ester of EPL. FIG.6E shows SEC-HPLC chromatograms showing nanochelator dimers and monomers along with NHS and EDC peaks of the reaction mixture (top) and base-treated reaction mixture (bottom), as well as a schematic diagram (right) for breaking EPL- dimers by adding sodium hydroxide. FIG.7A is a series of plots of the size-exclusion chromatography higher performance liquid chromatography (SEC-HPLC) for ZW-EPL- (top), ZW-DFO5-EPL- (middle top), EPL- (middle bottom), and DFO5-EPL- (bottom). FIG.7B is a series of 1H-NMR spectra of DFO and EPL conjugates in D2O. FIG.8A is a series of SEC-HPLC chromatograms of EPL, ZW-EPL, ZW-EPL-, ZW- DFO4-EPL-, ZW-DFO6-EPL-, ZW-DFO8-EPL-, and reagents used for chemistry. FIG.8B is a series of 1H-NMR spectra of EPL, EPL-, DFO3-EPL-, ZW-DFO4-EPL-, ZW-DFO6-EPL-, ZW- DFO8-EPL-, ZW-DFO5-EPL-, and DFO5-EPL-. FIG.8C is a series of MALDI-TOF mass spectra of EPL-, ZW-DFO4-EPL-, ZW-DFO6-EPL-, and ZW-DFO8-EPL-. FIG.9 is a table of the solubilities of DFO, ZW-DFO5-EPL-, and DFO5-EPL- in deionized water (DIW), 0.9% NaCl, 5% dextrose in water (D5W), dimethyl sulfoxide (DMSO), methanol (MeOH), ethanol (EtOH), and acetonitrile (ACN). FIG.10 is an absorbance spectrum (top) and emission spectrum excited at 660 nm (bottom) of ZW-DFO5-EPL- and DFO5-EPL-. FIG.11 is a plot of the viscosity of full and half-saturated DFO-EPL- formulations. Attorney Docket No.125141.04766.MGH2022-378 FIG.12 is a plot of iron chelation titration measured by UV-Vis spectroscopy at 430 nm of ZW-DFO5-EPL- (top) and DFO5-EPL- (bottom). FIG.13 shows SEC-HPLC spectra of protein binding of the nanochelators. FIG.14A is a series of Intraoperative color and NIR images of rats injected with ZW- DFO5-EPL- intravenously (IV, top) and subcutaneously (SC, bottom). FIG.14B is a plot of the signal-to-background ratio (SBR) of kidneys and bladder of the rats imaged in FIG.14A. FIG. 14C is a series of images of the resected major organs 4 h post-injection of rats injected with ZW-DFO5-EPL- via IV (top) and SC (bottom). FIG.14D is two quantitative SBR graphs of each organ (Org) compared to muscle (Mu) of rats injected with ZW-DFO5-EPL- via IV (left) and SC (right). Dotted lines indicate SBR=1. Bl, bladder; Du, duodenum; He, heart; In, intestine; Ki, kidney; Li, liver; Lu, lung; Pa, pancreas; Sp, spleen. FIG.15A shows blood curves (top) and organ distributions (bottom) of IV injected DFO5-EPL- 24 h prior to the measurement.3.3, 10, and 30 µmol / kg of DFO5-EPL- was injected IV or SC in SD rats (n = 2-4 per group, mean ± SD). FIG.15B shows blood curves (top) and organ distributions (bottom) of SC-injected DFO5-EPL- 24 h prior to the measurement.3.3, 10, and 30 µmol / kg of DFO5-EPL- was injected IV or SC in SD rats (n = 2-4 per group, mean ± SD). FIG.15C is a plot of the percent injected dose (%ID) of urine collected from IV- vs. SC- injected doses in serum. FIG.15D is a series of images of the histological examination of HE- stained tissues, including the liver, spleen, heart, kidney, and lung, for each treatment group. Scale bars = 100 μm. FIG.15E shows the biochemical analyses involved in the assessment of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine. Animal body weight was monitored for a period of 14 d following SC injection. A one-way ANOVA followed by Tukey’s multiple comparisons test was used to assess the statistical differences among more than two groups. p values <0.05 were considered significant: *p < 0.05, **p < 0.01, and ***p < 0.001. FIG.16A shows SEC-HPLC spectra of samples for intravenously injected rats at a dose of 30 µmol / kg IV (top) and 30 µmol / kg SC (bottom). FIG.16B shows serum standard curves of varying concentrations of DFO-EPL- precipitated from blank rat serum (top) and associated quadratic calibration curve (bottom). FIG.16C shows organ standard curves of varying concentrations of DFO-EPL- extracted from blank rat kidneys homogenates (top) and associated an associated linear calibration curve (bottom). FIG.16D shows organ standard curves of Attorney Docket No.125141.04766.MGH2022-378 varying concentrations of DFO-EPL- extracted from blank rat heart homogenates (top) and associated an associated linear calibration curve (bottom). FIG.17 is an overall scheme for the synthesis of DFO-EPL-. FIG.18 is a scheme of the synthesis of EPL-. FIG.19 is a SEC-HPLC spectrum of EPL-. FIG.20 is a MALDI-TOF spectrum of EPL-. FIG.21 is a scheme of the synthesis of DFO4-EPL-. FIG.22 is a SEC-HPLC spectrum of DFO-EPL-. FIG.23 is an 1H-NMR spectrum (D2O) of DFO-EPL-. FIG.24 is a MALDI-TOF spectrum of DFO-EPL-. DETAILED DESCRIPTION The present disclosure provides a compound of Formula I: (A)a—B Formula I or a pharmaceutically acceptable salt thereof, wherein: A is a labeling group or a group comprising a zwitterion; B is a biocompatible polymer substituted by C, -(D)d-E or a mixture thereof; each C is independently selected from the group consisting of H, OH, -(X1)m-(C(=Y1)- X2)n-R1, wherein, X1, X2 and Y1 are independently -NR1, O, or S; each D is an independently selected linking group; each E is an independently selected C or a metal chelating group; R1 is independently selected from H, OH, NR2R3, SR4, substituted or unsubstituted C1-6 alkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, aryl, heteroaryl, C1-6 alkoxy, aryloxy, or C1-6heteroalkoxy ; R2, R3 and R4 are independently selected from H, OH, substituted or unsubstituted C1-6 alkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, aryl, heteroaryl, C1-6 alkoxy, aryloxy, or C1-6heteroalkoxy; and a, d, m and n is 0 or 1, wherein at least one E is a metal chelating group. Attorney Docket No.125141.04766.MGH2022-378 In one embodiment, the compound of Formula I contains at least one metal chelating group. In some embodiments, A comprises a radioisotope labelled group, chromogenic group, fluorescent group, or one or more cationic groups each independently selected from the group consisting of ammonium, C1-6alkylammonium, di(C1-6alkyl)ammonium, tri(C1-6alkyl)ammonium, a cationic 5-10 membered heteroaryl group, and a cationic 4-10 membered heterocycloalkyl group, wherein the cationic 5-10 membered heteroaryl group and cationic 4-10 membered heterocycloalkyl group are each optionally substituted by 1, 2, 3, or 4 independently selected C1-6alkyl groups. In some embodiments, A comprises one or more cationic groups which are each independently selected from the group consisting of tri(C1-6 alkyl)ammonium and a cationic 5-10 membered heteroaryl group which is optionally substituted by 1, 2, 3, or 4 independently selected C1-6alkyl groups. In some embodiments, A comprises one or more cationic groups which are each independently selected from the group consisting of trimethylammonium and N-(C1-6 alkyl)indolium, wherein the N-(C1-6 alkyl)indolium is optionally substituted by 1 or 2 independently selected C1-6alkyl groups. In some embodiments, A comprises 1, 2, 3, or 4 cationic groups each independently selected from the group consisting of ammonium, C1-6 alkylammonium, di(C1-6 alkyl)ammonium, tri(C1-6alkyl)ammonium, a cationic 5-10 membered heteroaryl group, and a cationic 4-10 membered heterocycloalkyl group, wherein the cationic 5-10 membered heteroaryl group and cationic 4-10 membered heterocycloalkyl group are each optionally substituted by 1, 2, 3, or 4 independently selected C1-6alkyl groups. In some embodiments, A comprises 1, 2, 3, or 4 cationic groups which are each independently selected from the group consisting of tri(C1-6 alkyl)ammonium and a cationic 5-10 membered heteroaryl group which is optionally substituted by 1, 2, 3, or 4 independently selected C1-6alkyl groups. In some embodiments, A comprises 1, 2, 3, or 4 cationic groups which are each independently selected from the group consisting of trimethylammonium and N-(C1-6 alkyl)indolium, wherein the N-(C1-6alkyl)indolium is optionally substituted by 1 or 2 independently selected C1-6alkyl groups. Attorney Docket No.125141.04766.MGH2022-378 In some embodiments, A comprises one or more anionic groups each independently selected from the group consisting of oxide, carbonate, carboxylate, phosphate, sulfide, sulfinate, and sulfonate. In some embodiments, A comprises one or more anionic groups which are each sulfonate. In some embodiments, A comprises 1, 2, 3, or 4 anionic groups each independently selected from the group consisting of oxide, carbonate, carboxylate, phosphate, sulfide, sulfinate, and sulfonate. In some embodiments, A comprises 1 or 2 anionic groups each independently selected from the group consisting of oxide, carbonate, carboxylate, phosphate, sulfide, sulfinate, and sulfonate. In some embodiments, A comprises 1, 2, 3, or 4 anionic groups which are each sulfonate. In some embodiments, A comprises 1 or 2 anionic groups which are each sulfonate. In some embodiments, A is selected from the group consisting of formulas A-1, A-2, A- 3, A-4, A-5, and A-6: O RA

[0002] Attorney Docket No.125141.04766.MGH2022-378 X is selected from the group consisting of a bond, CH2, NH, -NH-C1-6alkylene-, O, and S; each RAis an independently selected anionic group; each RCis an independently selected cationic group; and L1, L2, and L3are each an independently selected C1-6alkylene group. In some embodiments, A is selected from the group consisting of formulas A-1 and A-2: O RA indicates the bond between A and B; X is selected from the group consisting of a bond, C, CH2, NH, O, Se, and S; each RAis an independently selected anionic group; each RCis an independently selected cationic group; and L1, L2, and L3are each an independently selected C1-6 alkylene group Attorney Docket No.125141.04766.MGH2022-378 In some embodiments, each RCis independently selected from the group consisting of ammonium, C1-6 alkylammonium, di(C1-6 alkyl)ammonium, and tri(C1-6 alkyl)ammonium. In some embodiments, each RCis an independently selected tri(C1-6alkyl)ammonium group. In some embodiments, each RCis trimethylammonium. In some embodiments, each RAis independently selected from the group consisting of oxide, carbonate, carboxylate, phosphate, sulfide, sulfinate, and sulfonate. In some embodiments, each RAis sulfonate. In some embodiments, L1is a C1-3 alkylene group. In some embodiments, L1is propylene. In some embodiments, L2is a C1-3alkylene group. In some embodiments, L2is propylene. In some embodiments, L1and L2are each an independently selected C1-3 alkylene group. In some embodiments, L1and L2are the same. In some embodiments, L1and L2are different. In some embodiments, L1and L2are each propylene. In some embodiments, L3is a C1-3 alkylene group. In some embodiments, L3is ethylene. In some embodiments, X is a bond. In some embodiments, X is selected from the group consisting of C, CH2, NH, -NH-C1-6alkylene-, O, Se, and S. In some embodiments, X is CH2. In some embodiments, X is selected from the group consisting of NH, -NH-C1-6 alkylene-, O, and S. In some embodiments, A is selected from the group consisting of: Attorney Docket No.125141.04766.MGH2022-378 In some embodiment, A contains a radioisotope labelled moiety or chromogenic moiety. Attorney Docket No.125141.04766.MGH2022-378 In some embodiments, A of the present compound does not include any group that comprises a zwitterion. In some embodiments, the present compound contains a labeling group A, which is different from formulas A-1, A-2, A-3, A-4, A-5, and A-6. In some embodiments, a is 0. In various embodiments, the present compound does not include a labeling group or a group comprising a zwitterion. In some embodiments, B is selected from the group consisting of a biocompatible polypeptide and a biocompatible polyester, each of which are substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, B is selected from the group consisting of polylysine, polylactic acid, poly(lactic-co-glycolic acid), polyaspartic acid, polyglutamic acid, polycaprolactone, polyglycolide, poly(ethylene glycol), and a copolymer thereof, each of which are substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, B is polylysine substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, the polylysine is ε-poly-L-lysine substituted by one or more C groups and one or more -(D)d-E groups. In some embodiments, B is: wherein: indicates the bond between B and A; indicates the monomeric units containing C or E are randomly connected; s is an integer from 2 to 50; and t is an integer from 1 to 20. Unless otherwise defined, it is understood that the monomeric units of the present compounds (such as those containing C or E above) are randomly connected, regardless of thepresence of the indicator “ ” in the formula. Attorney Docket No.125141.04766.MGH2022-378 In some embodiments, s is an integer from 2 to 30, for example, 2 to 30, 2 to 20, 2 to 10, 2 to 5, 5 to 30, 5 to 20, 5 to 10, 10 to 30, 10 to 20, or 20 to 30. In some embodiments, t is an integer from 1 to 10, for example, 1 to 10, 1 to 5, 1 to 3, 3 to 10, 3 to 5, or 5 to 10. In some embodiments, s is an integer from 5 to 30 and t is an integer from 1 to 10. In some embodiments, the hydrodynamic radius of B is from about 1 nm to about 10 nm, for example, about 1 nm to about 10 nm, about 1 nm to about 8 nm, about 1 nm to about 6 nm, about 1 nm to about 4 nm, about 1 nm to about 2 nm, about 2 nm to about 10 nm, about 2 nm to about 8 nm, about 2 nm to about 6 nm, about 2 nm to about 4 nm, about 4 nm to about 10 nm, about 4 nm to about 8 nm, about 4 nm to about 6 nm, about 6 nm to about 10 nm, about 6 nm to about 8 nm, or about 8 nm to about 10 nm. In some embodiments, each C is independently selected from the group consisting of hydrogen and an anionic group comprising one or more alkylene groups, one or more carbonyl groups, and one or more carboxyl groups. In some embodiments, C is an anionic group of the following formula: wherein: indicates the bond between C and B; p is an integer from 1 to 10. In some embodiments, In some embodiments, p is an integer from 1 to 5, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 2 to 5, 2 to 4, 2 to 3, 3 to 5, 3 to 4, or 4 to 5. In some embodiments, D is a linking group comprising one or more alkylene groups, one or more carbonyl groups, and one or more carboxyl groups. In some embodiments, D is a linking group of the following formula: Attorney Docket No.125141.04766.MGH2022-378 wherein: indicates the bond between D and B; indicates the bond between D and E; and q is an integer from 1 to 10. In some embodiments, q is an integer from 1 to 5, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, 2 to 5, 2 to 4, 2 to 3, 3 to 5, 3 to 4, or 4 to 5. In some embodiments, A is a group of formula A-1 or A-2: O RA indicates the bond between A and B; each RAis an independently selected anionic group; each RCis an independently selected cationic group; and L1, L2, and L3are each an independently selected C1-6 alkylene group; B is selected from the group consisting of a biocompatible polypeptide and a biocompatible polyester, each of which are substituted by one or more C groups and one or more -(D)d-E groups; C is an anionic group of the following formula: Attorney Docket No.125141.04766.MGH2022-378 wherein: indicates the bond between C and B; p is an integer from 1 to 10; D is a linking group of the following formula: wherein: indicates the bond between D and B; indicates the bond between D and E; and q is an integer from 1 to 10; and E is a metal chelating group. In some embodiments: A is a group of the following formula: wherein: indicates the bond between A and B; each RAis independently selected from the group consisting of oxide, carbonate, carboxylate, phosphate, sulfide, sulfinate, and sulfonate; Attorney Docket No.125141.04766.MGH2022-378 each RCis independently selected from the group consisting of ammonium, C1-6 alkylammonium, di(C1-6 alkyl)ammonium, and tri(C1-6 alkyl)ammonium; and L1, L2, and L3are each an independently selected C1-6alkylene group; B is selected from the group consisting of polylysine, polylactic acid, and poly(lactic-co- glycolic acid), polyaspartic acid, polyglutamic acid, polycaprolactone, polyglycolide, poly(ethylene glycol), and a copolymer thereof, each of which are substituted by one or more C groups and one or more -(D)d-E groups; C is an anionic group of the following formula: wherein: indicates the bond between C and B; p is an integer from 1 to 10; D is a linking group of the following formula: wherein: indicates the bond between D and B; indicates the bond between D and E; and q is an integer from 1 to 10; and E is a metal chelating group. In some embodiments: A is a group of the following formula: Attorney Docket No.125141.04766.MGH2022-378 wherein: each RAis sulfonate; each RCis tri(C1-6 alkyl)ammonium; and L1, L2, and L3are each an independently selected C1-6alkylene group; B is polylysine which is substituted by one or more C groups and one or more -(D)d-E groups; C is an anionic group of the following formula: wherein: indicates the bond between C and B; p is an integer from 1 to 5; D is a linking group of the following formula: wherein: indicates the bond between D and B; indicates the bond between D and E; and Attorney Docket No.125141.04766.MGH2022-378 q is an integer from 1 to 5; and E is a metal chelating group. In some embodiments, E is selected from the group consisting of an iron chelating group, a lead chelating group, and a copper chelating group. In some embodiments, E is an iron chelating group. In some embodiments, E is selected from the group consisting of an iron chelating group, a lead chelating group, a copper chelating group, an arsenic chelating group, a mercury chelating group, a manganese chelating group, a cadmium chelating group, a nickel chelating group, a chromium chelating group, a gold chelating group, and an antimony chelating group. Example metal chelating groups include, but are not limited to, deferoxamine, deferasirox and deferiprone (e.g., for chelating iron), D-penicillamine (e.g., for chelating copper), dimercaprol, (e.g., for chelating arsenic, mercury, lead, cadmium, nickel, chromium, gold, and / or antimony), dimercaptosuccinic acid (DMSA) (e.g., for chelating arsenic mercury, and / or lead), Calcium disodium EDTA (e.g., for chelating mercury and / or lead), and p-aminosalicyclic acid (e.g., for chelating manganese). In some embodiments, E is selected from the group consisting of an iron chelating group, a lead chelating group, a copper chelating group, an arsenic chelating group, a mercury chelating group, and a manganese chelating group. In some embodiments, E is an iron chelating group. In some embodiments, E is selected from the group consisting of dimercaptosuccinic acid, dimercaprol, ethylenediaminetetraacetic acid, p-aminosalicyclic acid, D-penicillamine, deferoxamine, deferiprone, and deferasirox. In some embodiments, E is deferoxamine. In some embodiments, the compound of Formula I is:

[0003] Attorney Docket No.125141.04766.MGH2022-378 or a pharmaceutically acceptable salt thereof, wherein indicates the monomeric units containing E2or E3are randomly connected; E1, E2, E3, and E4are independently C or a metal chelating group, wherein at least one of E1, E2, E3, or E4 is a metal chelating group; and s1 and t1 are independently an integer selected from 0-350, 2-250, 2-200, 3-150, 3-100, 3-75, 3-50, 3-40, or 3-35. Unless otherwise defined, it is understood that the monomeric units of the present compounds (such as those containing E2or E3above) are randomly connected, regardless of thepresence of the indicator “ ” in the formula.In another embodiment, the compound of Formula I is selected from: or Attorney Docket No. 125141.04766.MGH2022-378 E O3O , s is an integer from 5 to 50; t is an integer from 1 to 10; and E1-4are individually selected from the group consisting of OH or . In one aspect, the present disclosure provides a compound of formula (II), or a pharmaceutically acceptable salt thereof, O H wherein each R21is independently H or R22, wherein at least one R21is R22; R22 is –C(=O)C1-6-alkylene-C(=O)–R23; R23 at each occurrence is independently –OH or a metal (e.g., iron) chelating group, wherein at least one R23is a metal (e.g., iron) chelating group; and n2 is 10-50. The compound, or salt thereof, can be negatively charged (or in anionic form) under physiological condition (e.g., under pH 7.0-7.5, at a temperature of 35-40 ^C). For example, in the present compound or a salt thereof, the -NHR1moiety can form a positively charged group Attorney Docket No.125141.04766.MGH2022-378 (e.g., –NH3+, R21 is H) or a negatively charged group (e.g., R21 is –C(O)C1-6alkyleneC(O)–O-). In some embodiments, the number of positively charged -NHR1groups is less than the number of negatively charged -NHR21group in the same compound, thereby maintaining an overall negatively charged (anionic) state of the compound. In some embodiment, at least half of all the R21 groups are R22. In some embodiments, occurrence of R21being R22is t. The value of t can be at least 50%, at least 75%, at least 90%, at least 95% of the value of n. The value of t can be equal to n. For example, at least 10 (t ^10), at least 15 (t ^15), at least 20 (t ^20), at least 25 (t ^25), at least 30 (t ^30), at least 35 (t ^35), at least 40 (t ^40), or at least 45 (t ^45) R21 groups are R22. In some embodiments, each R21 of the present compound is R22. In some . In some n2 can be 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35. At least one R23 is the iron chelating group. In some embodiments, two or more R22 are – C(O)C1-6alkyleneC(O)–R23, in which R23 is the iron chelating group. In some embodiments, the occurrence of R3being the iron chelating group in Formula (II) is m, the value of which is understood to be a fraction of, or the same as, the value of the occurrence of R21being R22(t). In some embodiments, m is equal to t. In some embodiments, m is less than t. In some embodiments, m is less than one half of t. In some embodiments, m is 1-15. In some embodiments, m is 2-8. In some embodiments, m is 3, 4, 5, 6, 7, or 8. In particular embodiments, m is 4, 5, or 6. Example metal chelating groups include, but are not limited to, deferoxamine, deferasirox and deferiprone (e.g., for chelating iron), D-penicillamine (e.g., for chelating copper), dimercaprol, (e.g., for chelating arsenic, mercury, lead, cadmium, nickel, chromium, gold, and / or antimony), dimercaptosuccinic acid (DMSA) (e.g., for chelating arsenic mercury, and / or lead), Calcium disodium EDTA (e.g., for chelating mercury and / or lead), and p-aminosalicyclic acid (e.g., for chelating manganese). In some embodiments, the iron chelating group is deferoxamine, deferasirox, or deferiprone. In some embodiments, the iron chelating group is deferoxamine (DFO). For example, the deferoxamine moiety in Formula (II) is Attorney Docket No.125141.04766.MGH2022-378 . 8. For example, in these compounds, at least 10, at least 20, or at least 30 R21 groups are R22 (t ^10, t ^20, or t ^30), and in 4-8 of these R22 groups (represented by –C(O)C1-6alkyleneC(O)–R23) the R23group is the iron chelating group (m is 4-8). In these compounds, the iron chelating group can be deferoxamine. In some embodiments, n2 is 30-35 and m is 4, 5, or 6. In some embodiments, n2 is 32 and m is 4 or 5. In some embodiments, in the compound of formula (II) ; m is 4 or 5; and the iron chelating group is deferoxamine. Method of Preparation The present disclosure further provides methods of preparing the compounds provided herein and salts thereof. For example, the compounds of the present disclosure, e.g., compounds of Formula I or salts thereof, is prepared by steps of: a1) reacting a polymer with a linker to form a biocompatible polymer with a linker; and a2) reacting the biocompatible polymer with a linker prepared in the previous step with a metal chelating group to form a compound of Formula I. Alternatively, the compound of the present disclosure, e.g., compounds of Formula I) or salts thereof, is prepared by steps of: b1) reacting a metal chelating group with a selective protecting group to prepare a partially protected metal chelating group having one chemically active function moiety; Attorney Docket No.125141.04766.MGH2022-378 b2) reacting a polymer with a linker to form a biocompatible polymer with a linker; b3) reacting the partially protected metal chelating group with the biocompatible polymer with the linker from step b2) to form a protected compound of Formula I; and b4) deprotecting the protecting group on the metal chelating group to form a compound of Formula I. In another embodiment, the compound of the present disclosure, e.g., compounds of Formula I) or salts thereof, is prepared by steps of: c1) reacting a metal chelating group with a selective protecting group to prepare a partially protected metal chelating group having one chemically active function moiety; c2) reacting the partially protected metal chelating group with a linker to form a partially protected metal chelating group with a linker; c3) reacting the compound from the previous step c2) with a biocompatible polymer to form a protected compound of Formula I; and c4) deprotecting the protecting group on the metal chelating group to form the compound of Formula I. An example of synthesis of the compound of Formula I is provided in Scheme 1:

[0004] Attorney Docket No.125141.04766.MGH2022-378 of E1, E2, E3, or E4is a metal chelating group. In another aspect, the present disclosure provides a method of preparing an iron chelating compound of formula (II’), or a pharmaceutically acceptable salt thereof, wherein RAis H, R22, or a fluorophore; Attorney Docket No.125141.04766.MGH2022-378 each R21 is independently H or R22; RAand / or at least one R21 is R22; R22is –C(O)C1-6alkyleneC(O)–R23; R23 at each occurrence is independently –OH or an iron chelating group, wherein at least one R23 is the iron chelating group; and n is 10-50, the method comprising conjugating a precursor compound of formula (II’) in which R23 at each occurrence is –OH to an iron chelator in a reaction in the presence of 1- ethyl-3-(3-dimethyl aminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS), thereby producing the iron chelating compound. The present method can be used to prepare compounds of the Formula (I) or (II) as described herein. For example, the iron chelator can have a reactive hydroxy (–OH) or amino (– NH2) group, which is attached to the available carboxy groups (–COOH) in the precursor compound in a conjugation reaction to form the present iron chelating compound. In some embodiments, RAis a fluorophore. For example, the fluorophore is ZW800. In some embodiments, RAis H or R22. In some embodiments, occurrence of R23 being the iron chelating group is m. For example, m is 2-8. In some embodiments, m is 3, 4, 5, 6, or 7. In some embodiments, the present method further comprises converting epsilon-poly-l- lysine (EPL) to the precursor compound. It will be appreciated by one skilled in the art that the processes described are not the exclusive means by which compounds provided herein may be synthesized and that a broad repertoire of synthetic organic reactions is available to be potentially employed in synthesizing compounds provided herein. The person skilled in the art knows how to select and implement appropriate synthetic routes. Suitable synthetic methods of starting materials, intermediates and products may be identified by reference to the literature, including reference sources such as: Advances in Heterocyclic Chemistry, Vols.1-107 (Elsevier, 1963-2012); Journal of Heterocyclic Chemistry Vols.1-49 (Journal of Heterocyclic Chemistry, 1964-2012); Carreira, et al. (Ed.) Science of Synthesis, Vols.1-48 (2001-2010) and Knowledge Updates KU2010 / 1-4; 2011 / 1-4; Attorney Docket No.125141.04766.MGH2022-378 2012 / 1-2 (Thieme, 2001-2012); Katritzky, et al. (Ed.) Comprehensive Organic Functional Group Transformations, (Pergamon Press, 1996); Katritzky et al. (Ed.); Comprehensive Organic Functional Group Transformations II (Elsevier, 2ndEdition, 2004); Katritzky et al. (Ed.), Comprehensive Heterocyclic Chemistry (Pergamon Press, 1984); Katritzky et al., Comprehensive Heterocyclic Chemistry II, (Pergamon Press, 1996); Smith et al., March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6thEd. (Wiley, 2007); Trost et al. (Ed.), Comprehensive Organic Synthesis (Pergamon Press, 1991). Preparation of compounds described herein can involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by one skilled in the art. The chemistry of protecting groups can be found, for example, in T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rdEd., Wiley & Sons, Inc., New York (1999). Reactions can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g.,1H or13C), infrared spectroscopy, spectrophotometry (e.g., UV- visible), mass spectrometry, or by chromatographic methods such as high performance liquid chromatography (HPLC), liquid chromatography-mass spectroscopy (LCMS), or thin layer chromatography (TLC). Compounds can be purified by those skilled in the art by a variety of methods, including high performance liquid chromatography (HPLC) and normal phase silica chromatography. At various places in the present specification, divalent linking substituents are described. It is specifically intended that each divalent linking substituent include both the forward and backward forms of the linking substituent. For example, -NR(CR’R’’)n- includes both - NR(CR’R’’)n- and -(CR’R’’)nNR-. Where the structure clearly requires a linking group, the Markush variables listed for that group are understood to be linking groups. As used herein, the phrase “optionally substituted” means unsubstituted or substituted. As used herein, the term “substituted” means that a hydrogen atom is removed and replaced by a substituent. It is to be understood that substitution at a given atom is limited by valency. Attorney Docket No.125141.04766.MGH2022-378 Throughout the definitions, the term “Cn-m” indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include C1-4, C1-6, and the like. As used herein, the term “Cn-m alkyl” refers to a saturated hydrocarbon group that may be straight-chain or branched, having n to m carbons. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologs such as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl, 1,2,2- trimethylpropyl, and the like. In some embodiments, the alkyl group contains from 1 to 6 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbon atoms, or 1 to 2 carbon atoms. As used herein, the term “Cn-malkylene”, employed alone or in combination with other terms, refers to a divalent alkyl linking group having n to m carbons. Examples of alkylene groups include, but are not limited to, ethan-1,1-diyl, ethan-1,2-diyl, propan-1,1,-diyl, propan- 1,3-diyl, propan-1,2-diyl, butan-1,4-diyl, butan-1,3-diyl, butan-1,2-diyl, 2-methyl-propan-1,3- diyl, and the like. In some embodiments, the alkylene moiety contains 2 to 6, 2 to 4, 2 to 3, 1 to 6, 1 to 4, or 1 to 2 carbon atoms. As used herein, the term “ammonium” refers to a group of formula –NH3+. As used herein, the term “Cn-malkylammonium” refers to a group of formula –[NH2(Cn-m alkyl)]+, wherein the Cn-m alkyl refers to a saturated hydrocarbon group that may be straight-chain or branched, having n to m carbons, as defined herein. As used herein, the term “di(Cn-malkyl)ammonium” refers to a group of formula –[NH(Cn-m alkyl)2]+, wherein each Cn-m alkyl refers to an independently selected saturated hydrocarbon group that may be straight-chain or branched, having n to m carbons, as defined herein. As used herein, the term “tri(Cn-m alkyl)ammonium” refers to a group of formula –[N(Cn-m alkyl)3]+, wherein each Cn-m alkyl refers to an independently selected saturated hydrocarbon group that may be straight-chain or branched, having n to m carbons, as defined herein. As used herein, the term “carboxylate” refers to a group of formula “-COO-”. As used herein, the term “carbonate” refers to a group of formula “-CO32-”. As used herein, the term “heteroaryl” refers to a monocyclic aromatic heterocycle having at least one heteroatom ring member selected from sulfur, oxygen, and nitrogen. In some Attorney Docket No.125141.04766.MGH2022-378 embodiments, the heteroaryl ring has 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, the heteroaryl ring has 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen and sulfur. In some embodiments, any ring-forming N in a heteroaryl moiety can form an N-oxide. In some embodiments, the heteroaryl has 5-6 ring atoms and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, the heteroaryl has 5-6 ring atoms and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen and sulfur. In some embodiments, the heteroaryl has 5-6 ring atoms and 1 or 2 heteroatom ring members independently selected from nitrogen and sulfur. Exemplary five- membered ring heteroaryl groups include, but are not limited to, thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-triazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4- triazolyl, 1,3,4-thiadiazolyl, and 1,3,4-oxadiazolyl. Exemplary six-membered ring heteroaryl groups include, but are not limited to, pyridyl, pyrazinyl, pyrimidinyl, triazinyl and pyridazinyl. It is understood that a cationic heteroaryl group refers to a heteroaryl group as defined herein having one or more positive charges. Exemplary cationic heteroaryl groups include, but are not limited to, pyridium, pyrazinium, pyrimidinium, triazinium, and indolium. As used herein, “heterocycloalkyl” refers to non-aromatic monocyclic or polycyclic heterocycles having one or more ring-forming heteroatoms selected from O, N, or S. Included in heterocycloalkyl are monocyclic 4-, 5-, 6-, and 7-membered heterocycloalkyl groups. Heterocycloalkyl groups can also include spirocycles. Example heterocycloalkyl groups include pyrrolidin-2-one, 1,3-isoxazolidin-2-one, pyranyl, tetrahydropuran, oxetanyl, azetidinyl, morpholino, thiomorpholino, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, azepanyl, benzazapene, and the like. Ring-forming carbon atoms and heteroatoms of a heterocycloalkyl group can be optionally substituted by oxo or sulfido (e.g., C(O), S(O), C(S), or S(O)2, etc.). The heterocycloalkyl group can be attached through a ring- forming carbon atom or a ring-forming heteroatom. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 double bonds. Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused (i.e., having a bond in common with) to the cycloalkyl ring, for Attorney Docket No.125141.04766.MGH2022-378 example, benzo or thienyl derivatives of piperidine, morpholine, azepine, etc. A heterocycloalkyl group containing a fused aromatic ring can be attached through any ring-forming atom including a ring-forming atom of the fused aromatic ring. In some embodiments, the heterocycloalkyl has 4-10, 4-7 or 4-6 ring atoms with 1 or 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur and having one or more oxidized ring members. It is understood that a cationic heterocycloalkyl group refers to a heterocycloalkyl group as defined herein having one or more positive charges. Exemplary cationic heterocycloalkyl groups include, but are not limited to, oxetanium, azetidinium, morpholinium, and thiomorpholinium. At certain places, the definitions or embodiments refer to specific rings (e.g., an azetidine ring, a pyridine ring, etc.). Unless otherwise indicated, these rings can be attached to any ring member provided that the valency of the atom is not exceeded. For example, an azetidine ring may be attached at any position of the ring, whereas a pyridin-3-yl ring is attached at the 3- position. As used herein, the term “oxide” refers to a group of formula “-O-”. As used herein, the term “phosphate” refers to a group of formula “-PO43-”. As used herein, the term “sulfide” refers to a group of formula “-S-”. As used herein, the term “sulfinate” refers to a group of formula “-SO2-”. As used herein, the term “sulfonate” refers to a group of formula “-SO3-”. As used herein, the term “zwitterion” refers to a group comprising one or more positively charged groups (e.g., ammonium, C1-6 alkylammonium, di(C1-6 alkyl)ammonium, tri(C1-6 alkyl)ammonium, and the like) and one or more negatively charged groups (e.g., sulfinate, sulfonate, phosphate, oxide, and the like). As used herein, the term “metal ions” refers to free metal ions or metal ions bound to low affinity ligands (e.g., citrate), or a combination thereof, in a sample (e.g., a cell sample or tissue sample) or a subject. The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified. Attorney Docket No.125141.04766.MGH2022-378 Compounds provided herein also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone – enol pairs, amide – imidic acid pairs, lactam – lactim pairs, enamine – imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g. hydrates and solvates) or can be isolated. In some embodiments, preparation of compounds can involve the addition of acids or bases to affect, for example, catalysis of a desired reaction or formation of salt forms such as acid addition salts. Example acids can be inorganic or organic acids and include, but are not limited to, strong and weak acids. Some example acids include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, p-toluenesulfonic acid, 4-nitrobenzoic acid, methanesulfonic acid, benzenesulfonic acid, trifluoroacetic acid, and nitric acid. Some weak acids include, but are not limited to acetic acid, propionic acid, butanoic acid, benzoic acid, tartaric acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, and decanoic acid. Example bases include lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, and sodium bicarbonate. Some example strong bases include, but are not limited to, hydroxide, alkoxides, metal amides, metal hydrides, metal dialkylamides and arylamines, wherein; alkoxides include lithium, sodium and potassium salts of methyl, ethyl and t-butyl oxides; metal amides include sodium amide, potassium amide and lithium amide; metal hydrides include sodium hydride, potassium hydride and lithium hydride; and metal dialkylamides include lithium, sodium, and potassium salts of methyl, ethyl, n-propyl, iso-propyl, n-butyl, tert-butyl, trimethylsilyl and cyclohexyl substituted amides. In some embodiments, the compounds and salts provided herein are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or Attorney Docket No.125141.04766.MGH2022-378 substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compounds provided herein. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compounds provided herein, or salt thereof. Methods for isolating compounds and their salts are routine in the art. The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. The present application also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present application include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present application can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in aqueous solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, alcohols (e.g., methanol, ethanol, iso-propanol, or butanol) or acetonitrile (MeCN) are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p.1418 and Journal of Pharmaceutical Science, 66, 2 (1977). Conventional methods for preparing salt forms are described, for example, in Handbook of Pharmaceutical Salts: Properties, Selection, and Use, Wiley-VCH, 2002. Method of Use Attorney Docket No.125141.04766.MGH2022-378 The present application further provides methods of chelating metal ions in a sample (e.g. a cell sample or a tissue sample) or a subject, comprising contacting the sample with, or administering to the subject, a compound provided herein or (e.g., a compound of Formula I) or a pharmaceutically acceptable salt thereof. As used herein, the term “subject,” refers to any animal, including mammals. Example subjects include, but are not limited to, mice, rats, rabbits, dogs, cats, swine, cattle, sheep, horses, primates, and humans. In some embodiments, the subject is a human. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of a compound provided herein (e.g., a compound of any of Formula I), or a pharmaceutically acceptable salt thereof. In some embodiments, the method is a method of chelating metal ions in a cell or tissue sample, comprising contacting the cell sample or tissue sample with a compound provided herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the contacting forms a metal-compound chelate. The present application further provides a method of reducing the amount of free metal ions in a cell or tissue sample, comprising contacting the cell or tissue sample with a compound provided herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the contacting forms a metal-compound chelate, thereby reducing the amount of free metal ions in the cell or tissue sample. The present application further provides a method of chelating metal ions in a subject, comprising administering to the subject a therapeutically effective amount of a compound provided herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the metal ions are free metal ions or metal ions bound to low affinity ligands (e.g., citrate). The present application further provides a method of reducing the amount of free metal ions in a subject, comprising administering to the subject a compound provided herein, or a pharmaceutically acceptable salt thereof. The present application further provides a method of reducing the amount of metal ions (e.g., free metal ions or metal ions bound to low affinity ligands (e.g., citrate)), in the bloodstream of a subject in need thereof. In some embodiments, the method is a method of reducing the amount iron ions (e.g., free iron irons or iron ions bound to low affinity ligands (e.g., citrate)) in the bloodstream of a subject in need thereof. In some embodiments, the subject Attorney Docket No.125141.04766.MGH2022-378 has been determined to have high levels of iron ions (e.g., free iron irons or iron ions bound to low affinity ligands (e.g., citrate)) in the bloodstream compared to a subject having normal levels of iron ions in the bloodstream.  The present application further provides a method of reducing iron in a subject in need thereof, comprising administering to the subject a compound provided herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the method is a method of reducing iron overload in a subject in need thereof. The present application further provides a method of reducing the amount of metal ions bound to low affinity ligands in a subject, comprising administering to the subject a compound provided herein, or a pharmaceutically acceptable salt thereof. The present application further provides a method of reducing the amount of metal ions in a subject, comprising: i) diagnosing the subject as having an abnormal level of metal ions; and ii) administering to the subject a therapeutically effective amount of a compound provided herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the metal ions are free metal ions or metal ions bound to low affinity ligands (e.g., citrate). The present application further provides a method of reducing the amount of free metal ions in a subject, comprising: i) diagnosing the subject as having an abnormal level of free metal ions; and ii) administering to the subject a therapeutically effective amount of a compound provided herein, or a pharmaceutically acceptable salt thereof. The present compounds (e.g., negatively charged DFO-EPL-) can provide enhanced systemic circulation, absorption, and distribution of iron chelators (DFO). The present compounds (e.g., DFO-EPL-) can also facilitate efficient removal of excess iron exclusively via urinary elimination, while bypassing the immune system with negligible nonspecific tissue distribution. In particular embodiments, the blood half-life and urinary excretion of DFO-EPL- were 3-fold and 7-fold higher than native DFO, respectively. More importantly, systemically circulating DFO- EPL- reduced iron toxicity dramatically with no signs of DFO-mediated nephrotoxicity even at maximum tolerance doses. Together, these renal-clearable nanochelators can be used to markedly Attorney Docket No.125141.04766.MGH2022-378 elevate therapeutic efficacy and alleviate adverse effects associated with chelation therapy, thus enabling safer and more effective treatment of iron overload disorders in patients. In another aspect, the present disclosure provides a method of chelating iron ions in a subject, which comprises administering to the subject a therapeutically effective amount of a compound as described herein, or a pharmaceutically acceptable salt thereof. As used herein, the term “subject” refers to any animal, or a cell or tissue sample of the animal. The animal includes mammals. Example subjects include, but are not limited to, mice, rats, rabbits, dogs, cats, swine, cattle, sheep, horses, primates, and humans. In some embodiments, the subject is a human. The present application further provides a method of treating a disease or a disorder associated with an abnormal amount of free metal ions in a subject. The method can comprise administering a therapeutically effective amount of a composition comprising a compound as described herein, or a pharmaceutically acceptable salt thereof, to a subject in need thereof. Suitable diseases or disorders associated with an abnormal amount of free metal ions include those known in the art. In some embodiments, the disease or disorder is associated with an abnormal amount of free metal ions, an abnormal amount of metal ions bound to low affinity ligands (e.g., citrate), or a combination thereof. In some embodiments, the disease or disorder is thalassemia, myelodysplastic syndrome, sickle cell anemia, Blackfan Diamond anemia, rheumatoid arthritis, hemolysis, chronic iron overload due to transfusion-dependent anemias, acute kidney injury, traumatic brain injury, Alzheimer's disease, or a combination thereof. In some embodiments, the disease or disorder is associated with an abnormally high amount of metal ions in the subject (e.g., free metal ions, metal ions bound to low affinity ligands, or a combination thereof) compared to a subject having normal levels of metal ions. In some embodiments, the disease is associated with an abnormally high amount of free metal ions in the subject, compared to a subject having normal levels of free metal ions. In some embodiments, the disease is associated with an abnormally high amount of metal ions bound to low affinity ligands in the subject, compared to a subject having normal levels of metal ions bound to low affinity ligands in the subject. In some embodiments, the disease is associated with an abnormally high amount of a combination of free metal ions and metal ions bound to low Attorney Docket No.125141.04766.MGH2022-378 affinity ligands in the subject, compared to a subject having normal levels of free metal ions and metal ions bound to low affinity ligands. In some embodiments, the abnormal amount of metal ions in the subject refers to about 5% to about 100% increased concentration of metal ions in the subject compared to the concentration of metal ions in a normal subject, for example, about 5% to about 100%, about 5% to about 75%, about 5% to about 50%, about 5% to about 25%, about 5% to about 10%, about 10% to about 100%, about 10% to about 75%, about 10% to about 50%, about 10% to about 25%, about 25% to about 100%, about 25% to about 75%, about 25% to about 50%, about 50% to about 100%, about 50% to about 75%, or about 75% to about 100%, increased concentration of metal ions in the subject compared to the concentration of metal ions in a normal subject. In some embodiments, the abnormal amount of metal ions in the subject refers to about 2 fold to about 10 fold increased concentration of metal ions in the subject compared to the concentration of metal ions in a normal subject, for example, about 2 fold to about 10 fold, about 2 fold to about 8 fold, about 2 fold to about 5 fold, about 2 fold to about 3 fold, about 3 fold to about 10 fold, about 3 fold to about 8 fold, about 3 fold to about 5 fold, about 5 fold to about 10 fold, about 5 fold to about 8 fold, or about 8 fold to about 10 fold, increased concentration of metal ions in the subject compared to the concentration of metal ions in a normal subject. Methods of determining the concentration of metal ions in a subject are routine in the art and include, for example, measuring metal ions in a cell sample (e.g., NIR microscopy) or tissue sample (e.g., a biopsy sample by NIR spectroscopy) and / or measuring metal ions in the subject using an imaging technique (e.g., magnetic resonance imaging and / or optical fluorescence imaging). The present application further provides a method of treating a disease associated with an abnormal amount of free metal ions in a subject. In some embodiments, the method comprises administering to the subject a compound provided herein, or a pharmaceutically acceptable salt thereof. In one embodiment, the metal ion is iron ion. The present disclosure further provides a method of reducing the amount of free iron ions in a subject, comprising administering to the subject a therapeutically effective amount of a compound as described herein, or a pharmaceutically acceptable salt thereof. Attorney Docket No.125141.04766.MGH2022-378 The present disclosure further provides a method of reducing the amount of iron ions in the bloodstream of a subject in need thereof, which comprises administering to the subject a therapeutically effective amount of a compound as described herein, or a pharmaceutically acceptable salt thereof. The iron ions in the bloodstream include, for example, free iron ions or iron ions bound to low affinity ligands (e.g., citrate). In some embodiments, the subject has been determined to have high levels of iron ions (e.g., free iron irons or iron ions bound to low affinity ligands (e.g., citrate)) in the bloodstream compared to a subject having normal levels of iron ions in the bloodstream. The present application further provides a method of reducing the amount of iron ions in a subject, comprising: i) diagnosing the subject as having an abnormal level of metal ions; and ii) administering to the subject a therapeutically effective amount of a compound as described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the iron ions are free metal ions or metal ions bound to low affinity ligands (e.g., citrate). The present application further provides a method of treating a disease associated with an abnormal amount of iron ions in a subject, which comprises administering to the subject a therapeutically effective amount of a compound as described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the disease is associated with an abnormal amount of free iron ions, an abnormal amount of iron ions bound to low affinity ligands (e.g., citrate), or a combination thereof. As used herein, the term “abnormal amount” refers to comparison to a subject having normal levels of iron ions. In some embodiments, the abnormal amount of iron ions in the subject is about 5% to about 100% higher than the concentration of iron ions in a normal subject, including but not limited to about 5% to about 100%, about 5% to about 75%, about 5% to about 50%, about 5% to about 25%, about 5% to about 10%, about 10% to about 100%, about 10% to about 75%, about 10% to about 50%, about 10% to about 25%, about 25% to about 100%, about 25% to about 75%, about 25% to about 50%, about 50% to about 100%, about 50% to about 75%, or about 75% to about 100% higher than the concentration of iron ions in a normal subject. In some embodiments, the abnormal amount of iron ions in the subject is about 2 fold to about 10 fold higher than the concentration of metal ions in a normal subject, including but not limited to about 2 fold to about 10 fold, about 2 fold to about 8 fold, about 2 fold to about 5 fold, about 2 fold to about 3 fold, about 3 fold to about 10 fold, about 3 fold to about 8 fold, about 3 fold to Attorney Docket No.125141.04766.MGH2022-378 about 5 fold, about 5 fold to about 10 fold, about 5 fold to about 8 fold, or about 8 fold to about 10 fold higher than the concentration of metal ions in a normal subject. Methods of determining the concentration of iron ions in a subject are routine in the art and include, for example, measurement in a cell sample (e.g., NIR microscopy) or tissue sample (e.g., a biopsy sample by NIR spectroscopy) and / or measurement in the subject using an imaging technique (e.g., magnetic resonance imaging and / or optical fluorescence imaging). In another aspect, the present disclosure provides a method of treating a disease or disorder associated with iron overload disorders in a subject in need thereof. The method can comprise administering to the subject a therapeutically effective amount of a compound as described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the disease or disorder is thalassemia, myelodysplastic syndrome, sickle cell anemia, Blackfan Diamond anemia, rheumatoid arthritis, hemolysis, chronic iron overload due to transfusion-dependent anemias, acute kidney injury, traumatic brain injury, Alzheimer's disease, or a combination thereof. In some embodiments, the compounds provided herein, or pharmaceutically acceptable salts thereof, are administered to the subject in a therapeutically effective amount. As used herein, the phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response that is being sought in a tissue, system, animal, individual or human by a researcher, veterinarian, medical doctor or other clinician. As used herein, the term “treating” or “treatment” refers to one or more of (1) inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and / or symptomatology); and (2) ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and / or symptomatology) such as decreasing the severity of disease or reducing or alleviating one or more symptoms of the disease. Attorney Docket No.125141.04766.MGH2022-378 In some embodiments, the disease is associated with an abnormal amount of iron ions, an abnormal amount of lead ions, an abnormal amount of copper ions, an abnormal amount of arsenic ions, an abnormal amount of manganese ions, an abnormal amount of cadmium ions, an abnormal amount of nickel ions, an abnormal amount of chromium ions, an abnormal amount of gold ions, or an abnormal amount of antimony ions in the subject, or any combination thereof. In some embodiments, the disease is associated with an abnormal amount of iron ions, an abnormal amount of lead ions, or an abnormal amount of copper ions in the subject, or any combination thereof. In some embodiments, the disease is associated with an abnormal amount of iron ions, an abnormal amount of lead ions, or an abnormal amount of copper ions in the subject. In some embodiments, the disease is associated with an abnormal amount of iron ions in the subject. In some embodiments, the disease is selected from the group consisting of transfusion hemosiderosis (e.g., resulting from blood transfusions in a subject having one or more diseases selected from the group consisting of thalassemia, myelodysplastic syndrome, sickle cell anemia, and Blackfan Diamond anemia), hemochromatosis (e.g., hereditary or acquired), Wilson’s disease, copper poisoning, and heavy metal poisoning (e.g., lead poisoning, mercury poisoning, cadmium poisoning, arsenic poisoning, manganese poisoning, and the like). Pharmaceutical Compositions and Formulations When employed as pharmaceuticals, the compounds and salts provided herein can be administered via various routes (e.g., intravenous, intranasal, intradermal, or oral administration) in the form of pharmaceutical compositions. These compositions can be prepared as described herein or elsewhere, and can be administered by a variety of routes, depending upon whether local or systemic treatment is desired and upon the area to be treated. In some embodiments, the administration is parenteral. Parenteral administration includes, for example, intravenous, intraarterial, subcutaneous, intraperitoneal intramuscular or injection or infusion; or intracranial administration, (e.g., intrathecal or intraventricular, administration). Parenteral administration can be in the form of a single bolus dose, or may be, for example, by a continuous perfusion pump. In some embodiments, the compounds, salts, and pharmaceutical compositions provided herein are suitable for parenteral administration. In some embodiments, the compounds, salts, and pharmaceutical compositions provided herein are suitable for intravenous administration. Attorney Docket No.125141.04766.MGH2022-378 Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Also provided are pharmaceutical compositions which contain, as the active ingredient, a compound provided herein, or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers (e.g., excipients). In making the compositions provided herein, the active ingredient is typically mixed with an excipient, diluted by an excipient or enclosed within such a carrier in the form of, for example, a capsule, tablet, or other container. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), soft and hard gelatin capsules, suppositories, sterile injectable solutions, and sterile packaged powders. In some embodiments, the present pharmaceutical composition is an injectable composition. Some examples of suitable excipients include, without limitation, lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, and methyl cellulose. The formulations can additionally include, without limitation, lubricating agents such as talc, magnesium stearate, and mineral oil; wetting agents; emulsifying and suspending agents; preserving agents such as methyl- and propylhydroxy-benzoates; sweetening agents; flavoring agents, or combinations thereof. In some embodiments, the compounds provided herein, or pharmaceutically acceptable salts thereof, are administered to the subject in a therapeutically effective amount. As used herein, the phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response that is being sought in a tissue, system, animal, individual or human by a researcher, veterinarian, medical doctor or other clinician. As used herein, the term “treating” or “treatment” refers to one or more of (1) inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and / or symptomatology); and (2) Attorney Docket No.125141.04766.MGH2022-378 ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and / or symptomatology) such as decreasing the severity of disease or reducing or alleviating one or more symptoms of the disease. Dosage The active compound can be effective over a wide dosage range and is generally administered in a pharmaceutically effective amount. It will be understood, however, that the amount of the compound actually administered will usually be determined by a physician, according to the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered, the age, weight, and response of the individual subject, the severity of the subject’s symptoms, and the like. EXAMPLES The following examples are offered for illustrative purposes, and are not intended to limit the invention. Example 1. Methods & Materials Epsilon-poly-l-lysine (EPL; MW ≈ 4000) was purchased from BOC Sciences (Shirly, NY). Acetone, acetonitrile (ACN), anhydrous dimethyl sulfoxide (DMSO), deuterium oxide (D2O), dipyrrolidino(N-succinimidyloxy)carbenium hexafluorophosphate (HSPyU), ethanol (EtOH), ethyl acetate (EA), ethylenediaminetetraacetic acid disodium salt dihydrate (EDTA), ferric chloride, hydrochloric acid (6M), methanol (MeOH), N-(3-Dimethylaminopropyl)-N′-ethyl carbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS), ninhydrin reagent, sodium hydroxide, succinic anhydride (SA), and β-(N-morpholino)ethanesulfonic acid (MES) were purchased from Sigma-Aldrich (Saint Louis, MO), VWR Life Science (Radnor, PA) or Acros Organics (Morris Plains, NJ). Fetal bovine serum (FBS), phosphate-buffered saline (PBS) and rat serum were purchased from Fisher Scientific (Pittsburgh, PA). Deferoxamine mesylate (DFO) and assay reagent kits (aspartate aminotransferase, alanine aminotransferase, and serum creatinine) were purchased from Cayman Chemical (Ann Arbor, MI). Assay reagent kits for blood-urea nitrogen (BUN) were purchased from BioAssay Systems (Hayward, CA), Attorney Docket No.125141.04766.MGH2022-378 respectively.0.9% Sodium chloride injection and 5% dextrose injection were obtained from Hospira (Lake Forest, IL). Dialysis tubing was purchased from Repligen (Waltham, MA). Example 2. Synthesis of ZW-EPL. To conjugate NIR 800 nm emitting fluorophore ZW800-1C to EPL, previously reported protocols were followed. Briefly, EPL (366 µmol, 1.5 g) was dissolved in 150 mL of 1x PBS in a 250 mL round bottom flask. The pH was maintained at 8.0 by adding 6 M NaOH (750 µL). In a 50 mL falcon tube, ZW800-1C NHS ester (439 µmol, 450 mg) was dissolved in 18 mL DMSO with sonication. The dye solution was then added dropwise into the EPL solution with vigorous stirring. The pH was maintained at 8.0 by adding 6 M NaOH (aq) as needed, and the reaction mixture was precipitated after 3 h in 1.5 L of 20 v / v% EA / acetone. The precipitates were separated via centrifugation in 750 mL centrifuge bottles (2,000 rpm, 10 min) and the supernatant was decanted. The precipitates were combined and dissolved in a minimal amount of water (<20 mL) which was packaged in a 3.5 kDa molecular weight cut off (MWCO) regenerated cellulose (RC) dialysis membrane, and dynamic dialysis was performed for 12 h. After dialysis, the retentate was concentrated approximately 4x using rotary evaporation, and then syringe filtered (0.22 µm PES membrane) into a 50 mL tube, frozen, and lyophilized until completely dry. Example 3. Synthesis of ZW-DFO-EPL-. ZW-EPL (80 µmol, 400 mg) was dissolved in 40 mL of 1x PBS in a 100 mL round bottom flask with stirring. A 9.2 mL solution of succinic anhydride in DMSO (250 mg / mL) was prepared by dissolving SA in DMSO through sonication. This solution was added to the ZW- EPL containing flask with stirring, and 6 M NaOH (7.1 mL) was added to maintain a pH of 8.0. The reaction continued for 3 h, and the ninhydrin test was conducted to confirm reaction completion. The reaction mixture was then precipitated in 360 mL of EA in acetone (20 v / v%) and centrifuged to obtain a pellet, which was dissolved in water (20 mL) and dialyzed in a 12-14 kDa MWCO RC dialysis membrane for 24h under dynamic dialysis. After dialysis, the retentate was concentrated under rotary evaporation, frozen in a 50 mL tube, and lyophilized until dry. Attorney Docket No.125141.04766.MGH2022-378 Example 4. Succinylation of EPL. EPL (2.5 mmol, 10 g) was dissolved in 1 L of 1x PBS in a 2 L round bottom flask equipped with a magnetic stir bar. A 288 mL solution of SA in DMSO (250 mg / mL) was prepared by dissolving the succinic anhydride in DMSO through sonication in a 500 mL round bottom flask. This solution was added to the EPL containing flask under stirring, and the pH was adjusted to 8.0 by the addition of 52.75 g of NaOH pellets. The reaction was stirred for 3 h at room temperature, then the ninhydrin test was employed to confirm reaction completion (FIG. 2). The reaction mixture was precipitated in 9 L of EA in acetone (20 v / v%) and centrifuged in portions in 750 mL bottles to obtain several pellets, which were combined and dissolved in water (500 mL) and dialyzed in a 12-14 kDa MWCO RC dialysis membrane for 24 h under dynamic dialysis. After dialysis, the retentate was concentrated under rotary evaporation, frozen in 50 mL tubes, and lyophilized until dry. Example 5. DFO Conjugation to blank EPL-. 9000 mg of 2-(N-morpholino) ethanesulfonic acid (MES) was dissolved in 900 ml of distilled water to prepare a 0.1M MES solution.9 g of EPL- was added to the solution and dissolved via stirring. Alternatively, the EPL- may be dissolved via sonication. The pH was adjusted to 4.8 by adding 2.6 mL of 6M HCl. NHS and EDC were then added to the reaction flask. After dissolution, an additional 1350 µL of 6M HCl was added to the reaction flask to adjust the pH to 4.8 and the solution was stirred vigorously at 700 RPM for 15 minutes. DFO was then directly added to the reaction flask under stirring. The reaction mixture was neutralized to pH 7.3 by adding 20 mL of 6M NaOH and stirred for 24 hours. Thereafter, the reaction mixture was quenched by slightly basifying the solution to pH 8.4 with 2.25 mL 6M NaOH and 30 minutes of stirring. The reaction mixture was further basified by adding 225 µL 6M NaOH to pH 9.5 and immediately precipitating in 9L of 1:4 EA / Acetone. The precipitates were allowed to settle overnight. Alternatively, the suspension may be centrifuged in centrifuge bottles at 3000 RPM for 15 minutes. Thereafter, the supernatant is decanted. The precipitates were then dissolved in 70 mL distilled water, and 450 µL 6M HCl was used to neutralize the solution. The solution was then syringe filtered (0.22 µm PES membrane) and packaged in a 12-14 kDa MWCO RC dialysis membrane and dialyzed for 24 hours. The retentate was then concentrated using rotary evaporation, frozen in tubes, and lyophilized until completely dry. SEC-HPLC was Attorney Docket No.125141.04766.MGH2022-378 performed to confirm the purity and1H-NMR (10 ml sample / 0.6 ml D2O) was performed to calculate the DFO conjugation ratio. Example 6. Ninhydrin test. 20 µL of EPL- reaction mixture (2 mM), 20 µL of EPL (2 mM), and 20 µL of water (blank) were distributed into 20 mL scintillation vials, followed by the addition of 1 mL of ninhydrin reagent in ethanol (8 w / v%) with vigorous mixing. The vials were incubated in a preheated reaction block (100 ºC) for 5 min and then cooled in an ice bath for 3 min. After cooling, the solution was diluted with 4 mL of DIW and mixed, and the absorbance spectra of each sample were obtained with an Ocean Optics UV-Vis spectrometer. The presence of a peak at 570 nm, corresponding to Ruhemann’s Purple, indicates the presence of free amines, whereas the absence indicates full conversion of amines to succinate residues. Example 7. Size-exclusion chromatography analysis: The purity of nanochelators was measured using size exclusion chromatography (SEC) on the Waters HPLC system consisting of a Waters e2695 separations module and Waters 2998 PDA detector. The column used was a BioResolve SEC mAb 200Å, 2.5 µm 7.8^300 mm column equipped with a BioResolve SEC mAb 4.6x30 mm guard column, or a XBridge Protein BEH SEC 125Å, 3.5 µM 7.8x150 mm column equipped with a XBridge Protein BEH SEC 125Å, 3.5 µM 7.8x30 mm guard column. A 10 mM PBS mobile phase was used at a flow rate of 0.575 mL / min for 30 min, and 0.75 mL / min for 15 min, respectively. For the pharmacokinetics and biodistribution study, the previously mentioned XBridge column was used with a flow rate of 0.9 mL / min for 10.5 min for higher sample throughput. For urinalysis, flow rates vary between 0.75-0.9 mL / min for 15 to 10.5 min, respectively. Example 8. Hydrodynamic diameter analysis: To measure the hydrodynamic diameter (HD) of nanochelators, SEC was performed using the aforementioned XBridge Protein BEH SEC column, with the conditions described above to obtain the retention time (Rt) in min of the sample. A calibration curve was established by injecting 10 µL of a protein standard mixture (BEH125 SEC Protein Standard Mix; Waters) consisting of aprotinin (6.5 kDa, 1.96 nm), ribonuclease (13.7 kDa, 3.28 nm), ovalbumin (44 Attorney Docket No.125141.04766.MGH2022-378 kDa, 6.10 nm), and thyroglobulin (660 kDa, 17 nm). Uracil (112 Da) was included in the protein mixture but excluded from the calibration curve as it falls outside of the target HD range. The partition coefficient (Kav) was obtained for each protein by the following equation: Kav=(Ve- V0) / (Vc-V0), where V0, Vc, and Ve are column void volume (= 3.157 mL), geometric column volume (= 8.601 mL), and eluent volume, respectively, and where Ve= 0.75 ^^ Rt. The Kavof each protein was plotted against the logarithm of its HD, and a sigmoid curve was fit to the data. To find the HD of an unknown sample, the sample’s Rtis converted to Kavwhich can be plugged into the sigmoid curve equation to solve for HD. Example 9. MALDI-TOF mass spectrometry. Mass analyses were carried out using a Bruker UltrafleXtreme MALDI-TOF spectrometer. The spotting mixture was prepared by mixing a solution of sinapinic acid in acetonitrile (15 mg / mL) with 0.1% TFA in water in a 3:7 v / v ratio. This mixture was combined with a solution of each sample in water (25-75 mg / mL) in a 5:1 volume ratio. The dried droplet method deposited 0.3 µL of the final spotting mixture onto a MALDI plate. Spectra were acquired between 5 and 20 kDa in both linear positive and linear negative modes. Example 10. Solubility measurement of nanochelators. To determine the solubility of nanochelators in DIW, 0.9% NaCl, D5W, DMSO, ACN, MeOH, and EtOH, small portions (< 50 mg) of DFO, ZW-DFO5-EPL-, and DFO5-EPL- were weighed and constituted in 0.1-1.0 mL of respective solvent and then incubated for 45 min in an ultrasonic bath. Samples were allowed to cool to room temperature and then were centrifuged at 12 k^g for 10 min. The supernatant was collected and stored, and the remaining pellet was reconstituted in 200 µL of deionized water in a tared Eppendorf tube. The samples were frozen, lyophilized completely, and then weighed after complete drying. The remaining weight of the sample was subtracted from the initial weight to calculate the amount of sample dissolved. DFO samples were saturated with iron (III) chloride to produce a UV-detectable complex showing absorption at 430 nm. Calibration curves were established by measuring the absorbance of varying concentrations (0.5-2.0 mg / mL) of ZW-DFO5-EPL- and DFO5-EPL- at 760 nm and 430 nm, respectively, in each solvent. The absorbance spectrum was measured of the diluted saturated solution, and the concentration was determined by comparing the absorption at Attorney Docket No.125141.04766.MGH2022-378 respective wavelengths to a calibration curve and then accounting for initial dilution. This number was used to calculate the maximum solubility. Example 11. Viscosity measurement of DFO-EPL-. The viscosity of fully and half-saturated DFO-EPL- formulations was measured using a Haake Viscotester IQ Rheometer (Thermo Scientific, Germany) with a Peltier temperature- controlled bottom plate and a 25.0 mm stainless steel parallel plate measuring system. All measurements were performed at 25 °C with a 0.5 mm gap and 200 µL of sample. Viscosity (η’) was measured at an oscillation frequency of 1.2 Hz. Example 12. Physical and functional stoichiometry of nanochelators. The physical stoichiometry of DFO nanochelators was determined through1H-NMR measurements. All samples were prepared in 600 µL D2O with 0.05% wt. TMS (25 mg / mL). NMR spectra were acquired on a Varian 500 mHz with 128 scans. NMR peak assignments were deduced by comparing blank ZW-EPL- and DFO mesylate spectra to the spectra of either ZW- DFO-EPL- or DFO-EPL-. The conjugation ratio (m) of DFO to EPL was calculated by comparing the area under peaks from the DFO moiety and the polymer backbone; with nomenclature expressed as (ZW)-DFOm-EPL-. The functional stoichiometry of nanochelators was determined through an iron-chelating titration assay (FIGS.3A-3B). Briefly, 1 mL solutions of ZW-DFO4,5,6,8-EPL- and DFO5-EPL- were prepared at a concentration of 10 µM in water in a plastic cuvette.3.125 µL of 4 mM FeCl3 in water was added to the cuvette with thorough mixing, and the absorbance spectrum was measured. This process was repeated until the UV signal at 430 nm ceased to increase. By measuring the absorbance change at 430 nm, which represents the Fe3+and DFO complex, the functional stoichiometry was calculated by determining how many equivalents of iron were added until the UV absorbance signal was saturated. Example 13. Protein binding assay. The protein binding of ZW-DFO4-EPL- was determined by using an HPLC-SEC method. 30 µM ZW-DFO4-EPL- solutions in saline and 50% FBS (in saline) were incubated at 37 ºC in an orbital rocker for 24 h. The samples were then transferred to HPLC vials and injected to the column (10 µL), where the absorbance at 254 nm and 760 nm was monitored.50% FBS in saline Attorney Docket No.125141.04766.MGH2022-378 was run as a reference, and albumin protein binding was determined by observing the increase in peak area of the FBS incubated samples compared to samples in saline at the retention time of serum albumin proteins. Example 14. In vivo biodistribution and PK study. Animals were housed in an AAALAC- certified facility and studied under the supervision of MGH IACUC in accordance with the approved institutional protocol (#2021N000072). Six- week-old Sprague Dawley male rats (~200 g; Charles River Laboratories, Wilmington, MA) were maintained under general anesthesia by inhalation of isoflurane (Webster Veterinary, Fort Devens, MA). Rats were injected intravenously in the tail vein or subcutaneously in the left flank with 200 µL of ZW-DFO5-EPL- or DFO5-EPL- (3.3, 10 or 30 μmol / kg). After 1, 15 min, 4, 8, 12 h post-injection for IV injected rats, and 4, 12, 24 h for SC injected rats, the abdomen of rats was opened to image the organs in vivo, followed by organ excision and ex vivo imaging. Rats injected with ZW-DFO5-EPL- were imaged using the in-house built real-time intraoperative NIR imaging system. A 760 nm excitation laser source (4 mW cm-2) was used with white light (400– 650 nm; 40,000 lux), and color and NIR fluorescence images were acquired simultaneously with customized software. Example 15. Blood sample processing. Collected blood samples were processed into serum by centrifuging at 1500× for 15 min. Serum and urine were immediately frozen at -20 ºC and stored until quantified upon completion of the in-life portion of the study. Collected tissue samples were homogenized for the quantitation of DFO5-EPL- concentration. Tissues were dissected and 50–100 mg was transferred to a clean 2 mL tube with stainless steel beads and 100-200 µL methanol for homogenization in a Next Advance Bullet Blender. After homogenization and centrifugation, the supernatant was collected and filtered through a 0.22 µM HPLC filter vial prior to SEC-HPLC analysis. The concentration of DFO5-EPL- was determined using a standard curve which was generated by spiking blank rat organs with varying concentrations of the nanochelator. Blood and urine samples were precipitated in 9 times their volume in methanol. After centrifugation at 20 k^g for 10 min, the supernatant was filtered through an HPLC filter vial for SEC-HPLC analysis and the unknown concentration in serum and urine was determined by comparing to a Attorney Docket No.125141.04766.MGH2022-378 standard curve generated by spiking blank rat serum and urine with varying concentrations of nanochelator, respectively. Example 16. Quantitative and statistical analyses. Fluorescence and background intensities within specific tissue regions were measured using customized imaging software and ImageJ v1.51j8 (NIH, Bethesda, MD). To determine the signal-to-background ratio (SBR), we used the formula SBR = fluorescence intensity / Background intensity, with the background defined as the fluorescence level in the muscle tissue. A one-way ANOVA followed by Tukey’s multiple comparisons test was used to assess the statistical differences among more than two groups. p values <0.05 were considered significant: *p < 0.05, **p < 0.01, and ***p < 0.001. n.s., not significant. Example 17. Revisiting of ZW-DFO-EPL- chemistry. The previous synthetic method required a large excess of DFO (30 equivalence feed ratio; FIG.4) and 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (DMTMM), an amide coupling reagent, both of which are costly reagents which would account for a large percent of the cost of production in the industrial scale. To advance this platform into the preclinical stage and reduce associated costs, a more efficient and robust synthetic route based on EDC / NHS coupling chemistry was developed which allows for large-scale syntheses and precise control over the final conjugation ratio of DFO to the EPL backbone, from 4-8 DFO conjugated moieties per nanochelator (FIG.1A). The labeling ratio of DFO to ZW-EPL was defined as the molar equivalence of covalently attached DFO to one individual the backbone chain (FIG.5A). Since the PK and PD of nanochelators change as the DFO labeling ratio varies between 2 and 8, it is imperative to devise a reproducible synthetic strategy where precise control over the final conjugation ratio is made possible. Briefly, we optimized reaction parameters such as coupling agent feed ratio, DFO feed ratio, and reaction time systematically to yield nanochelators labeled with 2,4,5,6, and 8 DFO moieties, as well as their scale-up reaction conditions from 100 mg to 10 g (FIG.5A). ZW800-1C allows for real-time monitoring of the nanochelator in the body and the assessment of the PK and biodistribution using near-infrared (NIR) fluorescence imaging. The blood half-life of ZW-DFO-EPL- is 2 h and 6 h when administered intravenously (I.V.) and Attorney Docket No.125141.04766.MGH2022-378 subcutaneously (S.C.), respectively. To this end, an ultrasmall nanochelator DFO-EPL- was developed by eliminating the bulky fluorophore from the backbone (FIG.1B). The same optimization process using the conventional NHS chemistry was followed for large-batch DFO- EPL- (FIG.5B). Interestingly, when the same synthetic conditions were applied in a 1.4 g scale to DFO-EPL- in test reaction #11, the resulting conjugation ratio was found to be 2.8. To increase this ratio to the goldilocks number of 5.0, a similar method of varying the DFO feed ratio and observing the final conjugation ratio was employed in two 250 mg small-scale trials. It was found in reactions #12 and #13 that 7 equiv of DFO was necessary to obtain a conjugation ratio of 5. In fact, an even shorter reaction time of 1.5 h was implemented, which still yielded a consistent result (5.14), suggesting the conjugation reaction happens more quickly than previously expected. For large-scale 10-gram syntheses, the DFO feed ratio was increased slightly to 8, to account for the 40-fold increase in reaction scale, which also yielded satisfactory DFO conjugation ratios of 5 (+ / - 5%). The reason the DFO feed ratio for DFO-EPL- conjugation is higher than that of ZW-DFO-EPL- conjugation may be attributed to slight differences in solubility between the two nanochelators. The zwitterionic, ZW800-1C dye may disrupt the formation of a hydration shell around EPL which may hinder DFO from making a nucleophilic approach, therefore requiring excess DFO moieties for conjugation on the free EPL chain, to achieve a similar conjugation ratio of 5. Example 18. Minimization of polymer cross-linking. One of the major unwanted side reactions that occurs during the synthesis of both ZW- DFO-EPL- and DFO-EPL- is the cross-linking of two separate EPL chains. This can occur during the succinylation and DFO conjugation steps, which results in a species that is double the molecular weight, at 15 kDa, as determined by MALDI-TOF mass spectrometry (FIG.6A), and nearly 10 nm in diameter, as determined by SEC-HPLC (FIGS.6B-6C). It is hypothesized that the primary amine group of EPL can participate in a coupling side reaction with the terminal carboxylate group of a succinic anhydride (SA) residue from another EPL chain, forming a cross-link. To resolve this issue, excess SA was optimized to ensure complete succinylation of the EPL+ backbone and to minimize the frequency of cross-linking. It was found that the 9n equivalence of SA reduced the dimer formation to approximately 2% in a small scale (FIG.6B) and less than 2% in gram scales, confirmed by the HPLC chromatogram at 254 nm (FIG.7A). Attorney Docket No.125141.04766.MGH2022-378 Additionally, cross-linking is also observed in the DFO conjugation reaction, where the hydroxamic acid of DFO attacks an activated carbonyl carbon NHS ester on another EPL chain (Supplementary FIG.6C). To break this bond, we employed treatment with sodium hydroxide at the end of the reaction period, resulting in decreasing dimers from 21.2% to 2.3%, (FIG.6D). Additionally, base treatment can hydrolyze or quench any remaining activated NHS-ester moieties, returning them to the carboxylate form and preventing any unwanted amide coupling reactions afterward. After base treatment at pH 10.5, the reaction mixture is directly precipitated in acetone, where the solubility of DFO significantly increases. This precipitation step in acetone removes any unreacted DFO, while ZW-DFO-EPL- precipitates due to the difference in solubility. Then, the gel-like pellet was re-dissolved in water and underwent dynamic dialysis in a 12-14 kDa MWCO RC cellulose membrane against deionized water. The residual NHS, EDC, DFO, and any other byproducts were completely eliminated from the final product (Purity @254 nm; FIG. 8A). The purity was further confirmed by1H-NMR spectroscopy (FIG.7B) and MALDI-TOF mass spectrometry (FIGS.8B-8C). Example 19. Physicochemical and functional properties. The purified nanochelators were further applied to measure the physicochemical properties by using various analytical methods. The water solubility of DFO was improved significantly after introducing succinylated EPL- (8-fold for ZW-DFO5-EPL- and 10-fold for DFO5-EPL-, respectively). Interestingly, both nanochelators show high solubility in methanol (950 mg / mL), and virtually no solubility in ethanol or acetonitrile (≤ 1.0 mg / mL; FIG.9). This could be explained by the higher relative polarity of methanol (0.762) compared to ethanol (0.654) and acetonitrile (0.46). The hydrodynamic diameter (HD) of nanochelators was further investigated using SEC-HPLC, and found that HDs decreased gradually with DFO conjugation ratios from 6.12 nm (ZW-DFO4-EPL-) to 5.61 nm (ZW-DFO8-EPL-), as indicated in Table 1. This unexpected result may be attributed to the higher overall negative charge in less substituted polymers, which leads to repulsive electrostatic interactions causing the polymer to “spread out” in solution. Despite this observation, it was found that the overall HDs were still within the kidney filtration threshold (6-8 nm), indicating that DFO nanochelators can be readily excreted through renal glomerular filtration to urine. The optical properties of nanochelators were Attorney Docket No.125141.04766.MGH2022-378 measured by UV-Vis-NIR spectroscopy, where the absorbance peaks of DFO and ZW800-1C appear at 240 nm and 760 nm, respectively (FIG.10). To assess the injectability of various nanochelator formulations into blood, the viscosity of fully saturated (1,000 mg / mL) and half- saturated (500 mg / mL) solutions of DFO5-EPL- in deionized water (DIW), normal saline (NS), and 5% dextrose in water (D5W) were measured (FIG.11). The measured viscosities of the half- saturated DIW and NS formulations are less than that of blood (dotted line), indicating ideal viscosities for intravenous or subcutaneous injection. Protein binding of nanochelators, assessed through the SEC-HPLC assay, was found to be less than 1% (Table 1). Table 1. a Measured by MALDI-TOF and1H-NMR.b# of DFO per EPL was determined by Physiochemical Properties of various DFO-NPs f determined by size-exclusion chromatography high-performance liquid chromatography (SEC-HPLC), of monomer.eMeasured by SEC-HPLC after incubating each sample with fetal bovine serum (FBS) for 24 h.fDetermined based on the EPL chain length of n=32. N / D, not determined. By subtracting the area under the curve of the free ZW-DFO4-EPL- peak from the ZW- DFO4-EPL- FBS incubated peak with integration limits corresponding to that of the BSA elution Attorney Docket No.125141.04766.MGH2022-378 peak, the percent fraction of protein-bound ZW-DFO4-EPL- can be determined (FIG.13). It followed that virtually no protein binding occurs between ZW-DFO4-EPL- and BSA (0.9%), which would imply that the majority of nanochelators are available for iron chelation in the blood. This shows the ability of ZW-DFO4-EPL- to avoid nonspecific interactions, allowing for the specific chelation of excess iron in the blood before renal clearance. The functional properties of nanochelators were analyzed by utilizing an iron-binding assay to determine the absorbance at 430 nm of the DFO-iron complex (FIG.12). The findings indicate that the iron- binding stoichiometry values of ZW-DFO4-EPL- (4.6), ZW-DFO6-EPL- (6.6), and ZW-DFO8- EPL- (8.2) were in good agreement with those obtained by the physical stoichiometry method within acceptable ranges (<10% difference). Example 20. Biodistribution of ZW-DFO5-EPL- in rats. A key factor to the success of nanochelators is their ability to avoid nonspecific interactions and uptake by off-target organs. As shown in FIG.14A, ZW-DFO5-EPL- was accumulated in the kidneys 15 min post-injection and excreted exclusively to the urinary bladder by 4 h post-injection with minimal uptake in other major organs, such as the heart, lungs, liver, pancreas, spleen, and intestines, regardless of injection routes. The major signals in the bladder were observed up to 12 h for IV injection and 24 h for SC injection, respectively, suggesting sustained renal excretion at 12 h which decreases by 24 h (FIG.14B). Urinary excretion was measured over time, which is consistent with the imaging data. The biodistribution of ZW- DFO5-EPL- was assessed in major organs in vivo and ex vivo from different rats at various time points. FIG.14C shows representative color and NIR images of resected major organs 4 h post- injection, where major signals were found in the kidneys regardless of injection routes. The signal-to-background ratio (SBR) of each organ after being excised at different time points shows that all organs except the kidney in both IV and SC groups remain close to 1, indicating negligible uptake of nanochelators in off-target tissues and organs (FIG.14D). This is coincident with our previous report using ZW-DFO2-EPL-, ZW-DFO4-EPL-, and ZW-DFO8-EPL-, where only negligible signals were observed in the heart, lungs, liver, pancreas, spleen, duodenum, and intestines 4 h post-injection. Example 21. PK and biodistribution of DFO5-EPL- in rats. Attorney Docket No.125141.04766.MGH2022-378 To investigate how the dose and administration route affect the distribution and clearance of dye-free nanochelators, tissue homogenization was performed for quantitative analysis, focusing on major compartment organs such as the kidney, heart, lungs, liver, and spleen (FIGS. 14A-E and FIGS.16A-16D).3.3, 10, and 30 µmol / kg of DFO5-EPL- was injected both for IV and SC, and their PK was observed up to 24 h. In the tested dose range, IV-injected doses (FIG. 15A) showed 3-fold faster excretion compared to SC-injected doses (FIG.15B). The percent injected dose (%ID) of urinary excretion was measured by collecting urine using metabolic cages every 4 h intervals for up to 24 h post injections (FIG.15C). Overall, IV-injected doses showed faster urinary excretion compared to SC as the dose increased (*p < 0.05), which is consistent with the fluorescence imaging data obtained from ZW-DFO5-EPL- (FIGS.14A-14B). Interestingly, the content of DFO5-EPL- in the kidney ranged from 0.5 %ID / g to 0.2 %ID / g as the dose increased, represents passive excretion by glomerular filtration (FIG.15D), while DFO and ZW-DFO5-EPL- are reported to show glomerular filtration and saturable tubular secretion. The other major organs including heart, liver, and spleen, DFO5-EPL- showed a notable decrease as the dose increased (**p < 0.01 for all comparisons). Negligible quantities of DFO5-EPL- were detected in the rest of the organs (data not shown). The toxicity profile of DFO5-EPL- was assessed through biochemical assay. DFO5-EPL- significantly reduced markers associated with hepatotoxicity (AST and ALT, **p < 0.01) and nephrotoxicity compared to DFO alone, confirming the ability of the nanochelator to reduce the toxic effects of DFO. DFO5-EPL injected rats showed no significant differences in biomarkers compared to the saline group, indicating no toxicity. Additionally, the bodyweight of rats in the native DFO and DFO5-EPL group did not deviate from the control group over the 14 day test period. In conclusion, DFO-EPL- nanochelator was designed to address the challenges of short blood half-life and suboptimal pharmacokinetics of small molecule chelators and / or previously reported nanosized chelators. DFO-EPL- offers improved blood half-life and urinary excretion compared to native DFO, due to the enhanced systemic circulation, absorption, and distribution, resulting in efficient removal of excess iron primarily via urinary elimination. The biodistribution of nanochelators is influenced by the dose and administration route. negligible quantities of DFO-EPL- were observed in the kidneys, heart, lungs, liver, and spleen following IV and SC administration. Importantly, systemically circulating DFO-EPL- significantly reduces iron toxicity without signs of DFO-mediated nephrotoxicity. These results suggest that renal- Attorney Docket No.125141.04766.MGH2022-378 clearable nanochelators like DFO-EPL- have the potential to markedly improve therapeutic efficacy and alleviate the adverse effects associated with chelation therapy, thus offering a safer and more effective treatment of iron overload disorders in patients. Example 22. Synthesis of DFO4-EPL- DFO-EPL is based on the biocompatible and FDA GRAS polymer ^^-polylysine (EPL), or EPL+. The positively charged ammonium cations are converted to negatively charged succinate groups through a succinylation reaction. Charge modification of the nanoparticle is essential for controlling the nanochelator’s fate and preventing unwanted interactions in the body. Additionally, the side chain carboxylates present a site on which deferoxamine mesylate (DFO), an FDA approved small molecule iron chelator, can be installed in the next synthetic step through an amide coupling reaction. This DFO coupling reaction has been optimized to control the number of DFO moieties which are introduced onto each nanoparticle. In the final formulation, each nanochelator is outfitted with 4 DFO moieties, with ~28 negatively charged succinate side groups which impart an overall negative charge to the nanochelator. Since the biodistribution and PK of DFO-EPL can be changed by the surface charge, we control the conversion of carboxylates to be 100% by adding 9 equimolar succinic anhydrides to the amines of EPL. Example 23. Succinylation of EPL DFO’s iron-binding capacity is equimolar. An average of 4 DFO moieties on the carboxylates of DFO-EPL was introduced, which improves the overall avidity, without increasing the HD. DFO conjugation (n=4) forms the identical charge and ligand ratio to DFO- NPs. Table 2. Reagent MW Amount Mol Equiv. ) Attorney Docket No.125141.04766.MGH2022-378 6M NaOH (aq) 219.8 ml (52.75 g) ed with a magnetic stir bar. pH was maintained at ~8.0 by adding 6M NaOH (~5 mL). A succinic anhydride stock solution was prepared by dissolving 72 g in 288 ml of DMSO in a 500 ml conical tube. The succinic anhydride stock solution was added slowly into the EPL+tube under fast stirring. Increase pH to ~8.0 by adding ~219.8 ml 6M NaOH. The mixture was stirred for 3 hours and reaction completion was confirmed via the ninhydrin test. The reaction mixture was precipitated in 10 L acetone / EA (4 / 1). The precipitate was settled overnight or centrifuge the suspension in centrifuge bottles (3,000 rpm, 15 min) and decant the supernatant. The resulting solids were dissolved in about 1 L water, and the resulting solution was filtered through a syringe filter (0.22 µm PES membrane), and packaged in a 12-14kDa MWCO RC dialysis membrane. Dynamic dialysis was performed for 24 hours. The final solution was concentrated using rotary evaporation, followed by lyophillization until completely dry to obtain the product with an approximate yield >95%. Example 24. DFO conjugation: Table 3. Reagent MW Amount (g or vol) Mol Equiv. Attorney Docket No.125141.04766.MGH2022-378 6M HCl (aq) 5 ml 6M NaOH (aq) ~21.6 ml 900 ml of distilled water in a 2 L round bottom flask equipped with a magnetic stir bar, followed by adding 9 g of EPL- and mixing using stirring or sonication. About 2.6 mL of 6M HCl was added to lower the pH to about 4.8, followed by adding NHS and EDC to the reaction flask. After all were dissolved, an additional about 1350 µL of 6M HCl was added to return the pH to about 4.8. The resulting mixture was stirred for 15 minutes. DFO was added to the reaction mixture, followed by 20 mL of 6M NaOH to a pH of about 7.3. The resulting reaction mixture was stirred for 24 hours. After 24 hours, about 2.25 mL of 6 M NaOH solution was added to bring pH to 8.4, and the mixture was further stirred for 30 more minutes. The reaction mixture was basified with about 225 µL 6M NaOH (pH~9.5) and immediately precipitated in 9L of 1:4 EA / Acetone. The precipitates were allowed to settle overnight or the suspension was centrifuged (3,000 rpm, 15 min) to isolate the precipitates. The precipitates were dissolved in about 70 ml distilled water and about 450 µl 6M HCl was added to neutralize the solution. The solution was filtered through a syringe filter (0.22 µm PES membrane) if necessary and packaged in a 12-14kDa MWCO RC dialysis membrane, and dynamic dialysis was performed for 24 hours. The retentate was concentrated using rotary evaporation and lyophilized until completely dry to obtain the product in about 80% yield. The product was analyzed using SEC-HPLC to confirm purity and characterized by 1H-NMR (10 mg sample / 0.6 ml D2O) to calculate the DFO conjugation ratio. Example 25. Evaluation of EPL-DFO Conjugates in the Mouse Model of Ischemia- Reperfusion Acute Kidney Injury (IRI-AKI) The therapeutic efficacy of EPL-DFO Conjugates in the mouse model of AKI induced by ischemia-reperfusion injury (IRI) were evaluated. Acute kidney injury (AKI) is a serious complication in hospitalized patients with high level of mortality. There has not been much progress made for the past 50 years in reducing the mortality rate despite advances in understanding disease pathology. Scientists have tested therapeutic drugs that may reduce renal injury using a variety of animal models of acute kidney injury. Attorney Docket No.125141.04766.MGH2022-378 Material and Method The AKI model was generated on male C57BL / 6 mice at 9 weeks of age by bilateral IRI surgery. Mice were treated with 30 mg / kg DFO, EPL-DFO conjugate with Succinic acid linker, i.e. EPL-SA-DFO conjugates prepared using the similar procedures in the above examples (CR5 or CR7, conjugation ratio about 5 or 7 DFOs per conjugate) with DFO equivalent dose of 15 mg / kg or 30 mg / kg by subcutaneous injection once a day. The survival duration of mice after model generation was measured. Mice were euthanized for sample collection 24 hours after model generation. Blood was collected for the calculation of glomerular filtration rate (GFR), plasma biochemistry and analysis of free iron levels. The right kidney was collected for hematoxylin & eosin (H&E) and periodic acid-Schiff (PAS) staining for assessment of tubulointerstitial injury. EPL-DFO conjugates in 5 or 7 conjugates, i.e., CR5 or CR7 were each added to 800 µL of excipient (12% 2-hydroxypropyl-beta-cyclodextrin (Hp-β-CD), 38 % polyethylene glycol 400 (PEG400) and 50% water) in separate 5 mL tubes. The mixtures were vortexed for 3-4 minutes, followed by sonication in a water bath at 40°C for 25 minutes, using 8 minutes cycles to ensure complete dissolution. Once dissolved, the pH was adjusted by adding 20 µL of 0.5N NaOH incrementally, checking the pH after each addition. A total of 90-110 µL of NaOH was used to adjust the pH to 7.3 for CR5 and 7.2 for CR7. Finally, each solution was brought up to 1 mL with the excipient and mixed thoroughly. The final solutions were tested for stability by storing them at room temperature and 4°C for up to one week. In both conditions, the solutions remained stable, with no aggregates or sedimentation observed upon microscopic examination. For the generation of the IRI model, the mice were anesthetized with 4% isoflurane at induction, and then the isoflurane content was reduced to 2-2.5% for maintenance throughout the surgery procedure. The backside was shaved and sterilized using 70% ethanol and povidone. Both kidneys were exposed via flank incisions. The mice were subjected either to 30 minutes of bilateral renal ischemia and reperfusion injury or to a control sham-operation. Ischemia was induced by clamping both renal pedicles with non-traumatic microaneurysm clamps. After the removal of the clamps, reperfusion was confirmed by visual inspection. Treatment with 30 mg / kg CR5 significantly increased survival duration compared with treatment with vehicle, and increased the GFR of IRI model mice compared with vehicle Attorney Docket No.125141.04766.MGH2022-378 treatment. Treatment with EPL-DFO conjugates, CR5 or CR7, significantly reduced the ferrous iron content in the plasma. While treatment with 30 mg / kg DFO significantly reduced blood urea nitrogen levels, other plasma biomarkers were unaffected by treatment. Tubulointerstitial injury was not ameliorated by treatment. Body weight was measured every day for the duration of the study. In the case that the general health status of an animal was significantly worsened by the induced IRI-AKI, the mouse was euthanized and removed from the study. Definitions of acceptable endpoints include: no spontaneous movements and inability to drink or eat in 24 hour observation period, massive bleeding, spontaneous inflammation, missing anatomy, swelling or tumors larger than 20 mm, and inability to right itself in 30 sec period. The mice were monitored until death or the fulfillment of the euthanasia criteria. Survival Analysis The mice were monitored for survival on a daily basis. The survival duration was analyzed up to 7 days after model generation. The survival duration of the mice was recorded and presented as Kaplan Meier survival plots. Glomerular Filtration Rate FITC-sinistrin solution (5.6 mg / 100 g body weight) was injected via tail vein. Approximately 20 μL of blood was collected via retro-orbital vein sinus at 5, 15, 30 and 60 minutes postinjection of FITC-sinistrin. The standard was prepared by diluting FITC-sinistrin in mice plasma of the same background stain, and plasma FITC-sinistrin concentration was measured. The plasma FITC-sinistrin concentration was measured using a plate reader with excitation at 515 nm and emission at 582 nm. The glomerular filtration rate (GFR) was calculated using GraphPad Prism by using a two-phase exponential decay function. Tissue Sample Collection Necropsy was performed on mice to obtain plasma and kidney 24 hours after model generation. The mice were terminally anesthetized with ZoletilTM, and blood samples were collected by cardiac puncture. The whole blood was collected into heparin tubes, and plasma was Attorney Docket No.125141.04766.MGH2022-378 separated by centrifugation (3000 rpm for 15 min) at 4°C. Separated plasma was collected in Eppendorf microtubes, frozen on dry ice and stored at -80°C. The right kidney including the region of ureteral suture was isolated and fixed in 10% neutral buffered formalin (NBF) and embedded in paraffin before being sectioned. Samples were sectioned with a thickness of 5 µm using Leica Histocore AUTOCUT R (Leica Microsystems, Germany). Tissue sections were best mounted on Silane coated slides. The sections were stored at room temperature in preservative solutions until stained by antibodies. The left kidney was snap frozen and stored at -80°C. Result IRI model generation on day 0 resulted in reduced body weight in the model groups. Treatment did not significantly affect body weight compared with the vehicle-treated model group. Generation of the IRI model led to rapid deaths of the test animals. Survival duration of CR5 or CR7 was extended by about 25% compared with untreated group or DFO treated group.. The results suggest that EPL-DFO conjugates, CR5 or CR7, are effective in improving symptoms of AKI in the IRI mouse model. GFR was significantly reduced in IRI-AKI induced groups. GFR animals treated with EPL-DFO conjugates CR5 or CR7 at 30 mg / kg of DFO restored GFR to almost normal level, about 100% higher than DFO treated group. The plasma content of ferric iron was notably elevated in IRI-AKI induced group, and treatment with CR5 or CR7 reduced total iron level, i.e. Fe2+and Fe3+. Example 26. Evaluation of EPL-DFO Conjugates in the Mouse Model of Rhabdomyolysis induced AKI (RI-AKI) The therapeutic efficacy of EPL-DFO Conjugates in the mouse model of AKI induced by Rhabdomyolysis (RI-AKI) were evaluated. Rhabdomyolysis-induced acute kidney injury (RI-AKI) is a critical clinical condition resulting from the release of myoglobin and other nephrotoxic substances into the bloodstream following muscle breakdown. Attorney Docket No.125141.04766.MGH2022-378 Methods RI-AKI was induced in male C57BL / 6 mice (n = 89) by intramuscular injection of 50% glycerol (6.5 mL / kg) following 24-hour water deprivation. Mice were randomly assigned to four groups: control, RI-AKI + normal saline (NS), RI-AKI + DFO (30 mg / kg), and RI-AKI + DFO- EPL (100 mg / kg). Treatments were administered subcutaneously immediately after glycerol injection and continued daily until sacrifice at 96 hours. Kidney function was assessed by measuring blood urea nitrogen (BUN), serum creatinine, and urine output. Kidney tissues were analyzed via histology (H&E, PAS), immunohistochemistry, TUNEL staining, and western blotting to evaluate structural damage, apoptosis, inflammation, and fibrosis. Results Treatment with DFO and DFO-EPL conjugates attenuated kidney injury as evidenced by improved renal function markers and reduced histological damage. Both agents suppressed tubular apoptosis and inflammation, with DFO-EPL showing superior efficacy, 25% improved than DFO in survival rate, in reducing markers of fibrosis and inflammatory cytokines such as TNF-α and IL-6. DFO and DFO-EPL effectively mitigate renal injury in a mouse model of RI-AKI. DFO- EPL conjugates provided increased efficacy than DFO in about 25%. OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.125141.04766.MGH2022-378 CLAIMS 1. A compound of Formula I: (A)a—B Formula I or a pharmaceutically acceptable salt thereof, wherein: A is a labeling group or a group comprising a zwitterion; B is a biocompatible polymer substituted by one or more C groups and one or more – (D)d-E groups; each C is independently selected from the group consisting of H, OH, -(X1)m-C(=Y1)- (X2)n-R1, wherein, X1, X2 and Y1 are independently N, O, or S; R1 is selected from or H, OH, NR2R3, SH, substituted or unsubstituted C1-6 alkyl, C1-6 heteroalkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, aryl, heteroaryl, C1-6alkoxy, aryloxy, or C1-6heteroalkoxy ; each D is an independently selected linking group; each E is an independently selected C or a metal chelating group; and a, d, m and n is 0 or 1, wherein at least one E is a metal chelating group.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein A comprises one or more cationic groups each independently selected from the group consisting of ammonium, C1-6alkylammonium, di(C1-6alkyl)ammonium, tri(C1-6alkyl)ammonium, a cationic 5-10 membered heteroaryl group, and a cationic 4-10 membered heterocycloalkyl group, wherein the cationic 5-10 membered heteroaryl group and cationic 4-10 membered heterocycloalkyl group are each optionally substituted by 1, 2, 3, or 4 independently selected C1-6 alkyl groups.

3. The compound of claim 1, wherein B is a biocompatible polymer selected from a group consisting of polyalkylene oxide, such as polyethylene glycol, polypropylene glycol, a biocompatible polypeptide and a biocompatible polyester, or a copolymer thereof, wherein each of which is substituted by one or more C groups and one or more -(D)d-E groups.Attorney Docket No.125141.04766.MGH2022-378 4. The compound of claim 1, wherein B is selected from the group consisting of polylysine, polylactic acid, poly(lactic-co-glycolic acid), polyaspartic acid, polyglutamic acid, polycaprolactone, polyglycolide, poly(ethylene glycol), and a copolymer thereof, each of which is substituted by one or more C groups and one or more -(D)d-E groups.

5. The compound of claim 1, wherein B is polylysine substituted by one or more C groups and one or more -(D)d-E groups.

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein B is: wherein:indicates the bond between B and A; and wherein: the monomeric units containing C or E are randomly connected; s is an integer from 5 to 50; and t is an integer from 1 to 10.

7. The compound of claim 1, wherein each C is independently selected from the group consisting of hydrogen and an anionic group comprising one or more alkylene groups, one or more carbonyl groups, or one or more carboxyl groups, or any combination thereof.

8. The compound of claim 1, wherein C is an anionic group of the following formula:Attorney Docket No.125141.04766.MGH2022-378 O O R11wherein:indicates the bond between C and B; and R11 and R12 are independently selected from H, OH, substituted or unsubstituted C1-6 alkyl, C1-6heteroalkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, aryl, heteroaryl, C1-6alkoxy, aryloxy, or C1-6heteroalkoxy; and p is an integer from 1 to 10.

9. The compound of claim 1, wherein D is a linking group comprising one or more alkylene groups, one or more carbonyl groups, or one or more carboxyl groups, or any combination thereof.

10. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein D is a linking group of the following formula: O O E wherein:indicates the bond between D and B; indicates the bond between D and E; and R13and R14are independently selected from H, OH, substituted or unsubstituted C1-6alkyl, C1-6 heteroalkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, aryl, heteroaryl, C1-6 alkoxy, aryloxy, or C1-6 heteroalkoxy and q is an integer from 1-20, 2-15, 3-15, 3-12, 3-10 or 5-10.Attorney Docket No.125141.04766.MGH2022-378 11. The compound of claim 1, wherein E is selected from the group consisting of an iron chelating group, a lead chelating group, a copper chelating group, an arsenic chelating group, a mercury chelating group, and a manganese chelating group.

12. The compound of claim 1, wherein E is selected from the group consisting of dimercaptosuccinic acid, dimercaprol, ethylenediaminetetraacetic acid, p-aminosalicyclic acid, D-penicillamine, deferoxamine, deferiprone, and deferasirox.

13. The compound of claim 1, a is 0; B is selected from the group consisting of a biocompatible polypeptide and a biocompatible polyester, each of which is substituted by one or more C groups and one or more - (D)d-E groups; C is an anionic group of the following formula: O O R11D is a linking group ofO O R13B ERq14.

14. A pharmaceutical composition comprising the compound of claim 1, and a pharmaceutically acceptable carrier.

15. A method of treating a disease or a disorder associated with an abnormal amount of free metal ions in a subject comprising: administering a therapeutically effective amount of a composition comprising a compound of claim 1 to a subject in need thereof.Attorney Docket No.125141.04766.MGH2022-378 16. The method of claim 15, wherein the disease or disorder is thalassemia, myelodysplastic syndrome, sickle cell anemia, Blackfan Diamond anemia, rheumatoid arthritis, hemolysis, chronic iron overload due to transfusion-dependent anemias, acute kidney injury, traumatic brain injury, Alzheimer's disease, or a combination thereof.

17. A compound of formula (II), or a pharmaceutically acceptable salt thereof, whereineach R21 is or one is R22, wherein the monomeric units containing each R21are randomly connected; R22is –C(=O)C1-6-alkylene-C(=O)–R23; R23 at each occurrence is independently –OH or an iron chelating group, wherein at least one R23 is the iron chelating group; and n2 is 10-50.

18. A compound of claim 1 selected from the group consisting of: ,Attorney Docket No. 125141.04766.MGH2022-378 E3O 3 ,the monomeric units containing E2or E3are randomly connected; s is an integer from 5 to 50; t is an integer from 1 to 10; and E1-4are individually selected from the group consisting of OH or .

19. A method of preparing an iron chelating compound of formula (II’), or a pharmaceutically acceptable salt thereof,Attorney Docket No.125141.04766.MGH2022-378 wherein RAis H, R22, or a each R21 is independently H or R22, wherein the monomeric units containing each R21 are randomly connected; RAand / or at least one R21is R22; R22 is –C(O)C1-6alkyleneC(O)–R23; R23 at each occurrence is independently –OH or an iron chelating group, wherein at least one R23is the iron chelating group; and n is 10-50, the method comprising conjugating a precursor compound of formula (II’) in which R23 at each occurrence is –OH to an iron chelator in a reaction in the presence of EDC and NHS, thereby producing the iron chelating compound.

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