Modification of metallic surfaces with phosphonic acids

Abstract

Provided herein are methods and reagents for functionalization of metallic surfaces, including platinum, gold, palladium, iridium, and rhodium. The methods and reagents provided herein use phosphonic acid or phosphonate ester reagents as a source of attachment for various functionalities, thereby allowing modification of the surface with desired properties. The modified surfaces provided herein are useful for a variety of applications, including prevention of biofouling on metallic surfaces.

1 . A functionalized metallic surface comprising a metallic surface bound to a molecule having the structure: 
       
         
           
           
               
               
           
         
         wherein: 
         R is optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; and 
         wherein the metallic surface comprises at least one metal selected from platinum, gold, palladium, iridium, and rhodium, an oxide thereof, or any combination thereof. 
       
     
     
         2 . The functionalized metallic surface of  claim 1 , wherein R has the structure X-L-, wherein L is a linking moiety and X is a reactive handle or capture moiety, or R has the structure Y-L-, wherein L is a linking moiety and Y is a surface modification group. 
     
     
         3 . The functionalized metallic surface of  claim 2 , wherein L is an optionally substituted alkylene chain or optionally substituted heteroalkylene chain. 
     
     
         4 . The functionalized metallic surface of  claim 2  or  3 , wherein L has the structure of formula:
   —[Z—(CR 1 R 2 ) n ] m —
 
 wherein: 
 each R 1  and R 2  is independently H or optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl, or R 1  and R 2  on the same atom are taken together to form an oxo, or R 1 s on adjacent atoms are taken together to form a double bond, or R 1 s and R 2 s on adjacent atoms are taken together to form a triple bond; 
 each Z is independently absent, —O—, —NR 3 —, —S—, —SS—, —S(O)—, —S(O) 2 —, —C(O)—, —C(O)O—, —C(O)NR 3 , —OC(O)O—, —NR 3 C(O)NR 3 —, —OC(O)NR 3 —, —S(O) 2 O—, —S(O) 2 NR 3 —, —OS(O) 2 O—, —NR 3 SO 2 NR 3 —, or —OSO 2 NR 3 —; 
 each R 3  is independently H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl; 
 each n is independently an integer from 1 to 30; and 
 m is an integer from 1 to 30. 
 
     
     
         5 . The functionalized metallic surface of  claim 2  or  3 , wherein L comprises a chain of one to one hundred atoms, wherein each atom in the chain is independently selected from C, N, O, S, Si, and P. 
     
     
         6 . The functionalized metallic surface of  claim 5 , wherein the first atom in the chain is C. 
     
     
         7 . The functionalized metallic surface of any one of  claims 2 - 6 , wherein L comprises one or more subunits selected from 
       
         
           
           
               
               
           
         
       
       wherein each n is independently an integer from 1-30. 
     
     
         8 . The functionalized metallic surface of any one of  claims 2 - 7 , wherein L comprises the structure: 
       
         
           
           
               
               
           
         
         wherein each n is independently an integer from 1-30; and 
         each p is independently an integer from 1-30. 
       
     
     
         9 . The functionalized metallic surface of  claim 2 , wherein L comprises a polymer. 
     
     
         10 . The functionalized metallic surface of  claim 9 , wherein the polymer comprises a polyethylene, a polypropylene, a poly(vinyl halide), a polystyrene, a nylon, a polyamide, a polyester, a polyaramide, a polyacrylate, a poly methacrylate, a polytetrafluoroethylene, a polysaccharide, a poly(alkylene oxide), a poly(vinyl pyrrolidone), a poly(vinyl alcohol), a polyoxazoline, a poly(N-acryloyl morpholine), or any combination or derivative thereof. 
     
     
         11 . The functionalized metallic surface of any one of  claims 2 - 10 , wherein R has the structure: X-L-. 
     
     
         12 . The functionalized metallic surface of  claim 11 , wherein X comprises a reactive functional group selected from an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, acid, activated ester, alkene, alcohol, halide, acyl halide, sulfonic acid, sulfinic acid, sulfonyl halide, epoxide, aldehyde, ketone, imine, oxime, isocyanate, isothiocyanate, hydrazine, and hydrazide, or any combination thereof. 
     
     
         13 . The functionalized metallic surface of any one of  claims 2 - 10 , wherein X has the structure:
   X 1 -L X -Z X -   wherein Z X  is a bond, —O—, —NR 4 —, —S—, —SS—, —S(O)—, S(O) 2 —, —C(O)—, —C(O)O—, —C(O)NR 4 , —OC(O)O—, —NR 4 C(O)NR 4 —, —OC(O)NR 4 —, —S(O) 2 O—, —S(O) 2 NR 4 —, —OS(O) 2 O—, —NR 4 S(O) 2 NR 4 —, or —OS(O) 2 NR 4 —;   L X  is absent, optionally substituted alkylene, optionally substituted cycloalkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted arylene, optionally substituted arylalkylene, optionally substituted heteroarylalkylene, optionally substituted arylheteroalkylene, or optionally substituted heteroarylheteroalkylene;   X 1  comprises an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, carboxylic acid, activated ester, alkene, alcohol, acyl halide, sulfonic acid, sulfinic acid, sulfonyl halide, epoxide, aldehyde, ketone, imine, oxime, isocyanate, isothiocyanate, hydrazine, or hydrazide; and   each R 4  is independently H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl.   
     
     
         14 . The functionalized metallic surface of  claim 13 , wherein Z X  is a bond, —O—, —C(O)—, —NR 4 —, —C(O)O—, or —C(O)NR 4 . 
     
     
         15 . The functionalized metallic surface of  claim 13  or  14 , wherein L X  has the structure:
   —(CR 5 R 6 ) r —
 
 wherein each R 5  and R 6  is independently H, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl, or R 5  and R 6  on the same atom are taken together to form an oxo, or R 5 s on adjacent atoms are taken together to form a double bond, or R 5 s and R 6 s on adjacent atoms are taken together to form a triple bond; and 
 r is an integer from 0-30. 
 
     
     
         16 . The functionalized metallic surface of any one of  claims 13 - 15 , wherein X 1  is an amine, carboxylic acid, maleimide, azide, alkyne, halide, alkene, or sulfhydryl. 
     
     
         17 . The functionalized metallic surface of any one of  claims 11 - 16 , wherein X is 
       
         
           
           
               
               
           
         
         wherein: 
         R 5  and R 6  are each independently H or C 1 -C 3  alkyl; 
         r is 0 or 1; and 
         X 1  is azide, alkyne, halide, alkene, or sulfhydryl. 
       
     
     
         18 . The functionalized metallic surface of any one of  claims 11 - 17 , wherein X is 
       
         
           
           
               
               
           
         
       
     
     
         19 . The functionalized metallic surface of  claim 11 , wherein X comprises a capture moiety selected from biotin, avidin, streptavidin, a nucleic acid, a peptide, and a protein, or any combination thereof. 
     
     
         20 . A kit comprising the functionalized metallic surface of any one of  claims 11 - 19  and instructions for use. 
     
     
         21 . The functionalized metallic surface of any one of  claims 2 - 10 , wherein R has the structure Y-L-. 
     
     
         22 . The functionalized metallic surface of  claim 21 , wherein Y comprises a surface modification group selected from hydrophobic residues, hydrophilic residues, charged residues, cationic residues, anionic residues, polysaccharides, hydrophobic polymers, hydrophilic polymers, antimicrobial agents, biological materials, biocompatibility materials, anti-fouling materials, conductivity materials, semi-conductive materials, heat resistant materials, anti-corrosive material, catalysts, and magnetic materials, or any combination thereof. 
     
     
         23 . The functionalized metallic surface of  claim 21  or  22 , wherein Y has the structure
   Y 1 -L Y -Z Y - 
 wherein Z is a bond, —O—, —NR 4 —, —S—, —SS—, —S(O)—, S(O) 2 —, —C(O)—, —C(O)O—, —C(O)NR 4 , —OC(O)O—, —NR 4 C(O)NR 4 —, —OC(O)NR 4 —, —S(O) 2 O—, —S(O) 2 NR 4 —, —OS(O) 2 O—, —NR 4 S(O) 2 NR 4 —, —OS(O) 2 NR 4 —, or reaction product formed by a covalent bond forming reaction between an azide, alkyne, tetrazine, halide, sulfhydryl, disulfide, maleimide, amine, carboxylic acid, activated ester, alkene, alcohol, acyl halide, sulfonic acid, sulfinic acid, sulfonyl halide, epoxide, aldehyde, ketone, imine, oxime, isocyanate, isothiocyanate, hydrazine, or hydrazide and a suitable complementary reactive group; 
 L Y  is absent, optionally substituted alkylene, optionally substituted cycloalkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted arylene, optionally substituted arylalkylene, optionally substituted heteroarylalkylene, optionally substituted arylheteroalkylene, or optionally substituted heteroarylheteroalkylene; 
 Y 1  comprises at least one surface modification residue; and 
 each R 4  is independently H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, or optionally substituted heteroaryl. 
 
     
     
         24 . The functionalized metallic surface of  claim 23 , wherein Z is a bond, —O—, —NR 4 —, —S—, —SS—, —S(O)—, S(O) 2 —, —C(O)—, —C(O)O—, —C(O)NR 4 —, —OC(O)O—, —NR 4 C(O)NR 4 —, —OC(O)NR 4 —, —S(O) 2 O—, —S(O) 2 NR 4 —, —OS(O) 2 O—, —NR 4 S(O) 2 NR 4 —, —OS(O) 2 NR 4 —, 
       
         
           
           
               
               
           
         
       
     
     
         25 . The functionalized metallic surface of  claim 23  or  24 , wherein L is absent. 
     
     
         26 . The functionalized metallic surface of any one of  claims 23 - 25 , wherein Y 1  comprises hydrophobic residues. 
     
     
         27 . The functionalized metallic surface of  claim 26 , wherein the hydrophobic residues comprise a hydrophobic polymer. 
     
     
         28 . The functionalized metallic surface of  claim 27 , wherein the hydrophobic polymer comprises polyethylene, polypropylene, polystyrene, polyvinylhalide, polytetrafluoroethylene, poly(methyl methacrylate), polycarbonate, polyether-urethane, polydimethylsiloxane, or any combination or derivative thereof. 
     
     
         29 . The functionalized metallic surface of any one of  claims 26 - 28 , wherein the hydrophobic residues comprise fatty acids or derivatives thereof. 
     
     
         30 . The functionalized metallic surface of any one of  claims 23 - 25 , wherein Y 1  comprises hydrophilic residues. 
     
     
         31 . The functionalized metallic surface of  claim 30 , wherein the hydrophilic residues comprise a hydrophilic polymer. 
     
     
         32 . The functionalized metallic surface of  claim 31 , wherein the hydrophilic polymer comprises a polyacrylamide, a polyacrylate, a poly methacrylate, a poly(alkylene oxide), a poly(vinyl pyrrolidone), a poly(vinyl alcohol), a polyoxazoline, a poly(N-acryloyl morpholine), or any combination of derivative thereof. 
     
     
         33 . The functionalized metallic surface of  claim 31  or  32 , wherein the hydrophilic polymer comprises polyacrylamide, poly(N,N-diethylacrylamide), poly(N,N-dimethylacrylamide), poly(N-isopropylacrylamide), poly(acrylic acid), poly(methacrylic acid), poly(methyl acrylate), poly(ethyl acrylate), poly(2-hydroxyethyl acrylate), poly(propyl acrylate), poly(butyl acrylate), poly(methyl methacrylate), poly(2-hydroxyethyl methacrylate), poly(tetrahydrofurfuryl methacrylate), poly(ethylene oxide), poly(propylene oxide), poly(vinyl pyrrolidone), poly(oxazoline), poly(2-ethyloxazoline), or poly(N-acryloyl morpholine). 
     
     
         34 . The functionalized metallic surface of any one of  claims 21 - 25 , wherein Y comprises the structure: 
       
         
           
           
               
               
           
         
         wherein: 
         each R 7  is independently H, optionally substituted C 1 -C 3  alkyl or optionally substituted C 1 -C 3  hydroxyalkyl; 
         each R 8  is independently H or C 1 -C 3  alkyl; 
         each X 7  is independently absent, —O—, —S—, or —NR 9 ; 
         each R 9  is independently H or C 1 -C 6  alkyl; and 
         s is an integer from 1 to 10000. 
       
     
     
         35 . The functionalized metallic surface of any one of  claims 23 - 25 , wherein Y 1  comprises cationic residues. 
     
     
         36 . The functionalized metallic surface  claim 35 , wherein Y 1  comprises a cationic polymer. 
     
     
         37 . The functionalized metallic surface of  claim 35  or  36 , wherein the cationic residues comprise protonated amine groups, protonated substituted amine groups, quaternary amine groups, or any combination thereof. 
     
     
         38 . The functionalized metallic surface of any one of  claims 23 - 25 , wherein Y 1  comprises anionic residues. 
     
     
         39 . The functionalized metallic surface of  claim 38 , wherein Y 1  comprises an anionic polymer. 
     
     
         40 . The functionalized metallic surface of  claim 38  or  39 , wherein the anionic residues comprise carboxylates, sulfonates, sulfinates, phosphates, phosphonates, or any combination thereof. 
     
     
         41 . The functionalized metallic surface of any one of  claims 23 - 25 , wherein the surface modification group comprises hydrophobic residues, hydrophilic residues, charged residues, cationic residues, anionic residues, polysaccharides, hydrophobic polymers, hydrophilic polymers, antimicrobial agents, biological materials, biocompatibility materials, anti-fouling materials, conductivity materials, semi-conductive materials, heat resistant materials, anti-corrosive material, catalysts, magnetic materials, or any combination thereof. 
     
     
         42 . The functionalized metallic surface of any one of claims,  23 - 25 , wherein the surface modification group comprises a hydrogel. 
     
     
         43 . The functionalized metallic surface of  claim 42 , wherein the hydrogel comprises an acrylate, a methacrylate, an acrylamide, or a methacrylamide, or any combination thereof. 
     
     
         44 . The functionalized metallic surface of  claim 42  or  43 , wherein the hydrogel has a thickness from about 0.001 micron to about 10 microns. 
     
     
         45 . The functionalized metallic surface of any one of  claims 42 - 44 , wherein the hydrogel has a conductivity from about 0.1 S/m to about 10 S/m. 
     
     
         46 . The functionalized metallic surface of any one of the preceding claims, wherein at least about 1%, at least about 2%, at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% of the metallic surface is functionalized. 
     
     
         47 . The functionalized metallic surface of any one of the preceding claims, wherein the metallic surface is at least partially oxidized. 
     
     
         48 . The functionalized metallic surface of  claim 47 , wherein at least about 1%, at least about 2%, at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% of the metallic surface is oxidized. 
     
     
         49 . The functionalized metallic surface of any one of the preceding claims, wherein the metallic surface comprises a metal alloy. 
     
     
         50 . The functionalized metallic surface of  claim 49 , wherein the metal alloy comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% of the metal by weight. 
     
     
         51 . The functionalized metallic surface of any one of the preceding claims, wherein the metallic surface comprises the metal and an additional material. 
     
     
         52 . The functionalized metallic surface of any one of the preceding claims, wherein the metal surface comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% of the metal or any oxide of the metal by weight. 
     
     
         53 . The functionalized metallic surface of any one of the preceding claims, wherein the metal surface is configured to be placed inside the body of a mammal. 
     
     
         54 . The functionalized metallic surface of any one of the preceding claims, wherein the metal surface is a surgical or dental implant. 
     
     
         55 . The functionalized metallic surface of any one of the preceding claims, wherein the metal surface is an electrode, a microchip, a bead, a microparticle, or a nanoparticle. 
     
     
         56 . The functionalized metallic surface of any one of the preceding claims, wherein the metal is platinum or gold, or an oxide thereof. 
     
     
         57 . The functionalized metallic surface of any one of  claims 1 - 55 , wherein the metal is palladium, iridium, or rhodium, or an oxide thereof. 
     
     
         58 . A method of functionalizing a metallic surface comprising:
 (a) depositing a phosphonic acid or phosphonate ester reagent on a metallic surface; and   (b) heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metal surface;   wherein the metallic surface comprises platinum, gold, palladium, iridium, or rhodium, an oxide thereof, or any combination thereof.   
     
     
         59 . The method of  claim 58 , wherein depositing the phosphonic acid or phosphonate ester reagent comprises contacting the metallic surface with a solution comprising the phosphonic acid reagent and a solvent. 
     
     
         60 . The method of any one of  claim 58  or  59 , wherein the solvent comprises an organic solvent, an aqueous solvent, or any combination or mixture thereof. 
     
     
         61 . The method of  claim 60 , wherein the organic solvent comprises acetic acid, acetone, acetonitrile, benzene, tert-butyl alcohol, tert-butyl methyl ether, carbon tetrachloride, chloroform, cyclohexane, 1,2-dichloroethane, dichloromethane, diethyl ether, diglyme, 1,2,-dimethoxyethane, dimethyl acetamide, dimethylformamide, dimethyl sulfoxide, dioxane, ethanol, ethyl acetate, ethyl methyl ketone, ethylene glycol, hexanes, hexamethylphosphoramide, methanol, nitromethane, pentanes, 2-proponal, pyridine, tetrahydrofuran, toluene, xylenes, or any combination thereof. 
     
     
         62 . The method of  claim 60 , wherein the organic solvent comprises ethanol, tetrahydrofuran, or toluene. 
     
     
         63 . The method of any one of  claims 59 - 62 , wherein the phosphonic acid or phosphonate ester reagent is present in the solution at a concentration of up to about 1 μM, 10 μM, 100 μM, 1 mM, 10 mM, 100 mM, or 1 M. 
     
     
         64 . The method of any one of  claims 59 - 63 , wherein depositing the phosphonic acid or phosphonate ester reagent further comprises evaporating the solvent from the metallic surface. 
     
     
         65 . The method of  claim 64 , wherein evaporating the solvent from the metallic surface comprises heating the metallic surface. 
     
     
         66 . The method of  claim 65 , wherein the metallic surface is heated at a temperature of at least 30° C., at least 40° C., at least 50° C., at least 60° C., at least 70° C., at least 80° C., or at least 90° C. 
     
     
         67 . The method of any one of  claims 58 - 66 , wherein heating the metallic surface to bind the phosphonic acid reagent with the metallic surface occurs in an oven, a vacuum oven, or a microwave reactor. 
     
     
         68 . The method of any one of  claims 58 - 67 , wherein heating the metallic surface to bind the phosphonic acid or phosphonate ester reagent with the metallic surface comprises heating the metallic surface to a temperature of at least 30° C., at least 50° C., at least 70° C., at least 80° C., at least 100° C., at least 120° C., at least 140° C., at least 160° C., or at least 180° C. 
     
     
         69 . The method of any one of  claims 58 - 68 , wherein the metallic surface is an oxidized metallic surface. 
     
     
         70 . The method of  claim 69 , wherein the oxidized metallic surface is oxidized by air oxidation, plasma treatment, ultraviolet-ozone oxidation, or chemical oxidation. 
     
     
         71 . The method of any one of  claims 58 - 70 , further comprising the step of oxidizing the metallic surface. 
     
     
         72 . The method of  claim 71 , wherein oxidizing the metallic surface comprises plasma treatment, ultraviolet-ozone oxidation, or chemical oxidation. 
     
     
         73 . The method of any one of  claims 58 - 72 , wherein the phosphonic acid or phosphonate ester reagent has the structure: 
       
         
           
           
               
               
           
         
         wherein 
         R is optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; and 
         each R E  is independently H or optionally substituted alkyl. 
       
     
     
         74 . The method of any one of  claims 58 - 73 , wherein the metallic surface comprises platinum or gold, or an oxide thereof. 
     
     
         75 . The method of any one of  claims 58 - 73 , wherein the metallic surface comprises palladium, iridium, or rhodium, or an oxide thereof. 
     
     
         76 . A metallic surface microarray comprising a probe moiety bound to the metallic surface through a phosphonate residue, wherein the metallic surface comprises platinum, gold, palladium, iridium, or rhodium, or an oxide thereof, or any combination thereof. 
     
     
         77 . The microarray of  claim 76 , wherein the bound phosphonate residue has the structure: 
       
         
           
           
               
               
           
         
         wherein R comprises the probe moiety and each 
       
       
         
           
           
               
               
           
         
       
       indicates a point of attachment to the surface. 
     
     
         78 . The microarray of  claim 76  or  77 , wherein the probe moiety comprises a nucleic acid, a peptide, a protein, an antibody, a small molecule, a glycan, or any combination thereof. 
     
     
         79 . The microarray of  claim 78 , wherein the probe moiety comprises a nucleic acid. 
     
     
         80 . The microarray of  claim 79 , wherein the nucleic acid comprises DNA or RNA. 
     
     
         81 . The microarray of any one of  claims 76 - 80 , wherein the microarray is configured for DNA or RNA sequencing. 
     
     
         82 . The microarray of any one of  claims 76 - 81 , wherein the probe moiety binds a biological agent. 
     
     
         83 . The microarray of  claim 82 , wherein the biological agent is a nucleic acid, a protein, a cell, or an organelle. 
     
     
         84 . The microarray of any one of  claims 76 - 83 , wherein the probe moiety is specific for a biological agent. 
     
     
         85 . The microarray of any one of  claims 76 - 84 , wherein the microarray comprises at least 10, at least 100, at least 1000, at least 10000, or at least 100000 unique probe features. 
     
     
         86 . The microarray of any one of  claims 76 - 85 , wherein the metallic surface microarray comprises platinum or gold, or an oxide thereof. 
     
     
         87 . The microarray of any one of  claims 76 - 86 , wherein the metallic surface microarray comprises palladium, iridium, or rhodium, an oxide thereof, or any combination thereof. 
     
     
         88 . A drug delivery device comprising a drug moiety linked to a surface of the device through a phosphonate residue, wherein the surface comprises platinum, gold, palladium, iridium, or rhodium, an oxide thereof, or a combination thereof. 
     
     
         89 . The drug delivery device of  claim 88 , wherein the phosphonate residue has the structure: 
       
         
           
           
               
               
           
         
         wherein R comprises the drug moiety and each 
       
       
         
           
           
               
               
           
         
       
       indicates a point of attachment to the surface. 
     
     
         90 . The drug delivery device of  claim 88  or  89 , wherein the drug moiety is linked to the phosphonate residue through a linker. 
     
     
         91 . The drug delivery device of  claim 90 , wherein the linker is a cleavable linker. 
     
     
         92 . The drug delivery device of  claim 90  or  91 , wherein the linker is configured to release the drug moiety. 
     
     
         93 . The drug delivery device of any one of  claims 88 - 92 , further comprising a targeting moiety. 
     
     
         94 . The drug delivery device of  claim 93 , wherein the targeting moiety comprises an antibody or antibody fragment, a peptide, or a nucleic acid. 
     
     
         95 . The drug delivery device of any one of  claims 88 - 94 , wherein the drug delivery device is a nanoparticle, a microparticle, or a bead. 
     
     
         96 . The drug delivery device of any one of  claims 88 - 95 , wherein the surface comprises platinum or gold, an oxide thereof, or a combination thereof. 
     
     
         97 . The drug delivery device of any one of  claims 88 - 96 , wherein the surface comprises palladium, iridium, or rhodium, an oxide thereof, or a combination thereof. 
     
     
         98 . A functionalized metallic surface comprising a metallic surface bound to a molecule having the structure: 
       
         
           
           
               
               
           
         
         wherein 
         R comprises a hydrogel. 
       
     
     
         99 . The functionalized metallic surface of  claim 98 , wherein the metallic surface comprises platinum, gold, palladium, iridium, rhodium, silicon, aluminum, titanium, iron, zinc, zirconium, nickel, silver, copper, cobalt, or chromium, or an oxide thereof, or any combination thereof. 
     
     
         100 . The functionalized metallic surface of  claim 98  or  99 , wherein the hydrogel has a conductivity from about 0.001 S/m to about 10 S/m. 
     
     
         101 . The functionalized metallic surface of any one of  claims 98 - 100 , wherein the hydrogel has a thickness from about 0.001 microns to about 10 microns. 
     
     
         102 . The functionalized metallic surface of any one of  claims 98 - 101 , wherein the hydrogel comprises a synthetic polymer. 
     
     
         103 . The functionalized metallic surface of any one of  claims 98 - 102 , wherein the hydrogel comprises an acrylamide polymer. 
     
     
         104 . The functionalized metallic surface of any one of  claims 98 - 103 , wherein the acrylamide polymer is an N-substituted acrylamide, an N-substituted methacrylamide, a methacrylamide, or any combination thereof. 
     
     
         105 . The functionalized metallic surface of any one of  claims 98 - 104 , wherein the hydrogel comprises polyacrylamide, poly(diethyl acrylamide), poly(dimethyl acrylamide), poly(N-isopropylacrylamide), poly(acrylic acid), poly(methacrylic acid), poly(methyl acrylate), poly(ethyl acrylate), poly(2-hydroxyethyl acrylate), poly(propyl acrylate), poly(butyl acrylate), poly(methyl methacrylate), poly(2-hydroxyethyl methacrylate), poly(tetrahydrofurfuryl methacrylate), poly(ethylene oxide), poly(propylene oxide), poly(vinyl pyrrolidone), polyoxazoline, poly(2-ethyloxazoline), or poly(N-acryloyl morpholine). 
     
     
         106 . The functionalized metallic surface of any one of  claims 98 - 105 , wherein the metallic surface is an electrode. 
     
     
         107 . The functionalized metallic surface of any one of  claims 98 - 105 , wherein the metallic surface is positioned on an exterior surface of an electrode.