Heterocyclic-dithiol click chemistry

Abstract

Disclosed are polymers, methods of making polymers, and compositions, focused on cross-linking heterocycles comprising a moiety of Formula I with thiols and thiolates.

1 . A polymer derived from a first monomer and a first cross-linker, wherein
 the first monomer comprises at least two thiol functional groups;   the first cross-linker comprises a moiety of Formula I:   
       
         
           
           
               
               
           
         
         wherein 
         W is independently selected from the group consisting of S and Se; 
         Y is independently selected from the group consisting of S, Se, S(O), Se(O), S(O) 2  and Se(O) 2 ; and 
         X together with W and Y forms a substituted or unsubstituted 3-10-membered heterocyclic ring. 
       
     
     
         2 . The polymer according to  claim 1 , wherein the first monomer is selected from the group consisting of a dithiol compound, a trithiol compound, a tetrathiol compound, and a thiomer. 
     
     
         3 . The polymer according to  claim 1 , wherein the first monomer is selected from the group consisting of a dithiol compound, a trithiol compound, a tetrathiol compound, a hexathiol compound, and an octathiol compound. 
     
     
         4 . The polymer according to any one of  claims 1 - 3 , wherein the first monomer is selected from the group consisting of dithiothreitol (DTT), 1,2-ethanedithiol, 1,3-propanedithiol, 1,4-butanedithiol, 1,5-pentanedithiol, 1,6-hexanedithiol, 1,7-heptanedithiol, 1,8-octanedithiol, 1,9-nonanedithiol, 1,10-decanedithiol, 1,11-undecanedithiol, 1,12-dodecanedithiol, 1,13-tridecanedithiol, 1,14-tetradecanedithiol, 1,16-hexadecanedithiol, dithiolbutylamine (DTBA), tetra(ethylene glycol) dithiol, hexa(ethylene glycol) dithiol, 2-mercaptoethyl ether, 2,2′-thiodiethanethiol, 2,2′-(ethylenedioxy)diethanethiol, propane-1,2,3-trithiol, trimethylolpropane tris(2-mercaptoacetate), trimethylolpropane tris(3-mercaptoacetate), 3,3′,3″-((((1,3,5-triazine-2,4,6-triyl)tris(oxy))tris(propane-3,1-diyl))tris(sulfanediyl))tris(propane-1-thiol), 4,4′,4″-((((1,3,5-triazine-2,4,6-triyl)tris(oxy))tris(propane-3,1-diyl))tris(sulfanediyl))tris(butane-1-thiol), pentaerythrityl tetrathiol, pentaerythritol tetrakis(3-mercaptopropionate), a peptide having a disulfide bond, and a protein having a disulfide bond. 
     
     
         5 . The polymer according to any one of  claims 1 - 3 , wherein the first monomer is selected from the group consisting of poly(ethylene glycol) dithiol, 4arm-PEG2K-SH, 4arm-PEG5K-SH, 4arm-PEG10K-SH, 4arm-PEG20K-SH, 4-arm poly(ethylene oxide) thiol-terminated, 8arm-PEG10K-SH (hexaglyerol core), 8arm-PEG10K-SH (tripentaerythritol core), 8arm-PEG20K-SH (hexaglyerol core), 8arm-PEG20K-SH (tripentaerythritol core), and 8-arm poly(ethylene oxide) thiol-terminated. 
     
     
         6 . The polymer according to  claim 1 , wherein the first monomer is a peptide having a disulfide bond or a protein having a disulfide bond. 
     
     
         7 . The polymer according to  claim 6 , wherein the first monomer is a protein having a disulfide bond selected from the group consisting of a copper/zinc superoxide dismutase (SOD1) variant, a DJ-1 variant, an effector caspae, and iron-sulfur cluster assembly enzyme (IscU). 
     
     
         8 . The polymer according to  claim 7 , wherein the first monomer is a familial Amyotrophic Lateral Sclerosis (fALS)-SOD1 variant. 
     
     
         9 . The polymer according to any one of  claims 1 - 8 , wherein W and Y are S. 
     
     
         10 . The polymer according to any one of  claims 1 - 8 , wherein W is S and Y is S(O). 
     
     
         11 . The polymer according to any one of  claims 1 - 8 , wherein W and Y are Se. 
     
     
         12 . The polymer according to any one of  claims 1 - 8 , wherein W is Se and Y is Se(O). 
     
     
         13 . The polymer according to any one of  claims 1 - 8 , wherein W is Se and Y is S. 
     
     
         14 . The polymer according to any one of  claims 1 - 8 , wherein W is S and Y is Se. 
     
     
         15 . The polymer according to any one of  claims 1 - 8 , wherein W is Se and Y is S(O). 
     
     
         16 . The polymer according to any one of  claims 1 - 8 , wherein W is S and Y is Se(O). 
     
     
         17 . The polymer according to any one of  claims 1 - 16 , wherein
 X is —(CR 1 R 2 ) n —, wherein n is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8; and   each R 1  and each R 2  on each CR 1 R 2  group is independently selected from the group consisting of H, OH, NO 2 , CN, NH 2 , optionally substituted C 1 -C 2 alkyl, optionally substituted C 2 -C 12 alkenyl, optionally substituted C 2 -C 12 alkynyl, optionally substituted C 2 -C 12 heteroalkyl, optionally substituted C 3 -C 12 cycloalkyl, optionally substituted C 2 -C 12 heterocycloalkyl, optionally substituted C 2 -C 12 heterocycloalkenyl, optionally substituted C 6 -C 18  aryl, optionally substituted C 1 -C 18 heteroaryl, optionally substituted C 1 -C 12 alkyloxy, optionally substituted C 2 -C 12 alkenyloxy, optionally substituted C 2 -C 12 alkynyloxy, optionally substituted C 2 -C 12 heteroalkyloxy, optionally substituted C 3 -C 12 cycloalkyloxy, optionally substituted C 3 -C 12 cycloalkenyloxy, optionally substituted C 1 -C 12 heterocycloalkyloxy, optionally substituted C 2 -C 12 heterocycloalkenyloxy, optionally substituted C 6 -C 18 aryloxy, optionally substituted C 1 -C 18 heteroaryloxy, optionally substituted C 1 -C 12 alkylamino, CONR 3 R 4 , NR 3 COR 4 , NR 3 COOR 4 , NR 3 SO 2 R 4 , NR 3 CONR 3 R 4 , and NR 3 R 4 ; and   wherein each R 3  and R 4  is independently selected from the group consisting of: H, optionally substituted C 1 -C 12 alkyl, optionally substituted C 2 -C 12 alkenyl, optionally substituted C 2 -C 12 alkynyl, optionally substituted C 2 -C 12 heteroalkyl, optionally substituted C 3 -C 12 cycloalkyl, optionally substituted C 3 -C 12 cycloalkenyl, optionally substituted C 2 -C 12 heterocycloalkyl, optionally substituted C 2 -C 12 heterocycloalkenyl, optionally substituted C 6 -C 18 aryl, and optionally substituted C 1 -C 18 heteroaryl.   
     
     
         18 . The polymer according to  claim 17 , wherein n is an integer selected from the group consisting of 3, 4, 5, and 6. 
     
     
         19 . The polymer according to  claim 17  or  18 , wherein each R 1  and each R 2  on each CR 1 R 2  group is independently selected from the group consisting of H, OH, NO 2 , CN, NH 2 , optionally substituted C 1 -C 12 alkyl, optionally substituted C 2 -C 12 heteroalkyl, optionally substituted C 3 -C 12 cycloalkyl, optionally substituted C 2 -C 12 heterocycloalkyl, optionally substituted C 1 -C 12 alkyloxy, optionally substituted C 2 -C 12 heteroalkyloxy, optionally substituted C 3 -C 12 cycloalkyloxy, and optionally substituted C 1 -C 12 heterocycloalkyloxy. 
     
     
         20 . The polymer according to any one of  claims 17 - 19 , wherein each R 1  and each R 2  on each CR 1 R 2  group is independently selected from the group consisting of H, OH, NO 2 , CN, NH 2 , optionally substituted C 1 -C 12 alkyl, optionally substituted C 3 -C 12 cycloalkyl, optionally substituted C 1 -C 12 alkyloxy, and optionally substituted C 3 -C 12 cycloalkyloxy. 
     
     
         21 . The polymer according to any one of  claims 1 - 8  and  17 - 20 , wherein the first cross-linker comprises a moiety of Formula I selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         22 . A method for covalent coupling of molecules comprising
 providing a plurality of first molecules comprising a moiety of Formula I:   
       
         
           
           
               
               
           
         
         wherein 
         W is independently selected from the group consisting of S and Se; 
         Y is independently selected from the group consisting of S, Se, S(O), Se(O), S(O) 2  and Se(O) 2 ; and 
         X together with W and Y forms a substituted or unsubstituted 3-10-membered heterocyclic ring; and 
         contacting the first molecules with a plurality of second molecules comprising at least one thiol functional group; 
         thereby forming a plurality of covalent bonds between the S or Se atoms of the first molecule and the free thiol groups of the second molecule. 
       
     
     
         23 . A method of coating a surface of an object, a device, or an assembly, comprising the steps of:
 (a) providing a surface of an object, a device, or an assembly;   (b) contacting the surface with a plurality of first molecules comprising a reactive moiety and a moiety of Formula I:   
       
         
           
           
               
               
           
         
         
           wherein 
           W is independently selected from the group consisting of S and Se; 
           Y is independently selected from the group consisting of S, Se, S(O), Se(O), S(O) 2  and Se(O) 2 ; and 
           X together with W and Y forms a substituted or unsubstituted 3-10-membered heterocyclic ring; 
         
         thereby forming a plurality of covalent bonds between the surface and the reactive moieties of the first molecule to form a first monolayer. 
       
     
     
         24 . The method according to  claim 23  further comprising
 (c) contacting the monolayer with a second molecule comprising at least one thiol functional group, thereby forming a first bilayer, wherein a plurality of covalent bonds are formed between the S or Se atoms of the first molecule and the free thiol groups of the second molecule. 
 
     
     
         25 . The method according to  claim 24  further comprising
 (d) applying an electrical potential, thereby reducing the covalent bonds, thus forming a second monolayer. 
 
     
     
         26 . The method according to  claim 25  further comprising
 (f) providing an aqueous mixture comprising water and a plurality of metal ions, thereby forming a complex, comprising a plurality of metal-chelating groups of the second monolayer chelated to the plurality of metal ions, thus forming a second bilayer. 
 
     
     
         27 . The method according to  claim 26 , wherein the plurality of metal-chelating groups are S atoms. 
     
     
         28 . The method according to  claim 27 , wherein the plurality of metal-chelating groups are Se atoms. 
     
     
         29 . The method according to any one of  claims 26 - 28 , wherein the plurality of metal ions are a plurality of metal cations. 
     
     
         30 . The method according to  claim 29 , wherein the metal cation has a charge of +1. 
     
     
         31 . The method according to  claim 30 , wherein the metal cation is a cation of Ag or Au. 
     
     
         32 . The method according to  claim 29 , wherein the metal cation has a charge of +2. 
     
     
         33 . The method according to  claim 32 , wherein the metal cation is a cation of Ca, Cd, Co, Cr, Cu, Er, Fe, Hg, Mg, Mn, Nb, Ni, Pb, Pd, Sc, Sn, Sr, V, or Zn. 
     
     
         34 . The method according to  claim 29 , wherein the metal cation has a charge of +3. 
     
     
         35 . The method according to  claim 34 , wherein the metal cation is a cation of Au, Ce, Dy, Er, Eu, Fe, Gd, Ho, La, Lu, Nb, Nd, Pm, Pr, Sm, Tb, Tm, or Yb. 
     
     
         36 . The method according to any one of  claims 26 - 35  further comprising
 (f) contacting the second bilayer with a plurality of third molecules comprising a moiety of Formula I: 
 
       
         
           
           
               
               
           
         
         
           wherein 
           W is independently selected from the group consisting of S and Se; 
           Y is independently selected from the group consisting of S, Se, S(O), Se(O), S(O) 2  and Se(O) 2 ; and 
           X together with W and Y forms a substituted or unsubstituted 3-10-membered heterocyclic ring; 
           thereby forming a trilayer, wherein the plurality of third molecules are chelated to the plurality of metal ions. 
         
       
     
     
         37 . The method according to any one of  claims 22 - 36 , wherein W and Y are S. 
     
     
         38 . The method according to any one of  claims 22 - 36 , wherein W is S and Y is S(O). 
     
     
         39 . The method according to any one of  claims 22 - 36 , wherein W and Y are Se. 
     
     
         40 . The method according to any one of  claims 22 - 36 , wherein W is Se and Y is Se(O). 
     
     
         41 . The method according to any one of  claims 22 - 36 , wherein W is Se and Y is S. 
     
     
         42 . The method according to any one of  claims 22 - 36 , wherein W is S and Y is Se. 
     
     
         43 . The method according to any one of  claims 22 - 36 , wherein W is Se and Y is S(O). 
     
     
         44 . The method according to any one of  claims 22 - 36 , wherein W is S and Y is Se(O). 
     
     
         45 . The method according to any one of  claims 22 - 44 , wherein
 X is —(CR 1 R 2 ) n —, wherein n is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8; and   each R 1  and each R 2  on each CR 1 R 2  group is independently selected from the group consisting of H, OH, NO 2 , CN, NH 2 , optionally substituted C 1 -C 2 alkyl, optionally substituted C 2 -C 12 alkenyl, optionally substituted C 2 -C 12 alkynyl, optionally substituted C 2 -C 12 heteroalkyl, optionally substituted C 3 -C 12 cycloalkyl, optionally substituted C 2 -C 12 heterocycloalkyl, optionally substituted C 2 -C 12 heterocycloalkenyl, optionally substituted C 6 -C 18  aryl, optionally substituted C 1 -C 18 heteroaryl, optionally substituted C 1 -C 12 alkyloxy, optionally substituted C 2 -C 12 alkenyloxy, optionally substituted C 2 -C 12 alkynyloxy, optionally substituted C 2 -C 12 heteroalkyloxy, optionally substituted C 3 -C 12 cycloalkyloxy, optionally substituted C 3 -C 12 cycloalkenyloxy, optionally substituted C 1 -C 12 heterocycloalkyloxy, optionally substituted C 2 -C 12 heterocycloalkenyloxy, optionally substituted C 6 -C 18 aryloxy, optionally substituted C 1 -C 18 heteroaryloxy, optionally substituted C 1 -C 12 alkylamino, CONR 3 R 4 , NR 3 COR 4 , NR 3 COOR 4 , NR 3 SO 2 R 4 , NR 3 CONR 3 R 4 , and NR 3 R 4 ; and   wherein each R 3  and R 4  is independently selected from the group consisting of: H, optionally substituted C 1 -C 12 alkyl, optionally substituted C 2 -C 12 alkenyl, optionally substituted C 2 -C 12 alkynyl, optionally substituted C 2 -C 12 heteroalkyl, optionally substituted C 3 -C 12 cycloalkyl, optionally substituted C 3 -C 12 cycloalkenyl, optionally substituted C 2 -C 12 heterocycloalkyl, optionally substituted C 2 -C 12 heterocycloalkenyl, optionally substituted C 6 -C 18 aryl, and optionally substituted C 1 -C 18 heteroaryl.   
     
     
         46 . The method according to any one of  claims 22 - 45 , wherein the first molecule comprises a moiety of Formula I selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         47 . The method according to any one of  claims 22  and  24 - 46 , wherein the second molecule is selected from the group consisting of (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide, (11-mercaptoundecyl)hexa(ethylene glycol), (11-mercaptoundecyl)tetra(ethylene glycol), 1-(11-mercaptoundecyl)imidazole, 1-mercapto-2-propanol, 11-(1H-pyrrol-1-yl)undecane-1-thiol, 11-(ferrocenyl)undecanethiol, 11-amino-1-undecanethiol hydrochloride, 11-azido-1-undecanethiol, 11-mercapto-1-undecanol, 11-mercaptoundecanamide, 11-mercaptoundecanoic acid, 11-mercaptoundecylhydroquinone, 11-mercaptoundecylphos-phonic acid, 12-mercaptododecanoic acid, 16-amino-1-hexadecanethiol hydrochloride, 16-mercaptohexadecanamide, 16-mercaptohexadecanoic acid, 3-amino-1-propanethiol hydrochloride, 3-chloro-1-propanethiol, 3-mercapto-1-propanol, 3-mercaptopropionic acid, 4-mercapto-1-butanol, 6-(ferrocenyl)hexanethiol, 6-amino-1-hexanethiol hydrochloride, 6-mercapto-1-hexanol, 6-mercaptohexanoic acid, 8-amino-1-octanethiol hydrochloride, 8-mercapto-1-octanol, 8-mercaptooctanoic acid, 9-mercapto-1-nonanol, triethylene glycol mono-1-mercaptoundecyl ether, 1-mercaptosuccinic acid, a peptide having a cysteine residue, a protein having a cysteine residue, cysteamine, 1-thiohexitol, poly(ethylene glycol) 2-mercaptoethyl ether acetic acid, poly(ethylene glycol) methyl ether thiol, 1-thioglycerol, 2-naphthalenethiol, biphenyl-4-thiol, 3-amino-1,2,4-triazole-5-thiol, 5-(trifluoromethyl)pyridine-2-thiol, 1-[2-(dimethylamino)ethyl]-1H-tetrazole-5-thiol, 1-propanethiol, 1-butanethiol, 1-pentanethiol, 1-hexanethiol, 1-octanethiol, 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanethiol, and γ-Glu-Cys. 
     
     
         48 . The method according to any one of  claims 22  and  24 - 46 , wherein the second molecule is selected from the group consisting of a dithiol compound, a trithiol compound, a tetrathiol compound, and a thiomer. 
     
     
         49 . The method according to any one of  claims 22  and  24 - 46 , wherein the second molecule is selected from the group consisting of a dithiol compound, a trithiol compound, a tetrathiol compound, a hexathiol compound, and an octathiol compound. 
     
     
         50 . The method according to any one of  claims 22 ,  24 - 46 ,  48 , and  49 , wherein the second molecule is selected from the group consisting of DTT, 1,2-ethanedithiol, 1,3-propanedithiol, 1,4-butanedithiol, 1,5-pentanedithiol, 1,6-hexanedithiol, 1,7-heptanedithiol, 1,8-octanedithiol, 1,9-nonanedithiol, 1,10-decanedithiol, 1,11-undecanedithiol, 1,12-dodecanedithiol, 1,13-tridecanedithiol, 1,14-tetradecanedithiol, 1,16-hexadecanedithiol, DTBA, tetra(ethylene glycol) dithiol, hexa(ethylene glycol) dithiol, 2-mercaptoethyl ether, 2,2′-thiodiethanethiol, 2,2′-(ethylenedioxy)diethanethiol, propane-1,2,3-trithiol, trimethylolpropane tris(2-mercaptoacetate), trimethylolpropane tris(3-mercaptoacetate), 3,3′,3″-((((1,3,5-triazine-2,4,6-triyl)tris(oxy))tris(propane-3,1-diyl))tris(sulfanediyl))tris(propane-1-thiol), 4,4′,4″-((((1,3,5-triazine-2,4,6-triyl)tris(oxy))tris(propane-3,1-diyl))tris(sulfanediyl))tris(butane-1-thiol), pentaerythrityl tetrathiol, pentaerythritol tetrakis(3-mercaptopropionate), a peptide having a disulfide bond, and a protein having a disulfide bond. 
     
     
         51 . The method according to any one of  claims 22 ,  24 - 46 ,  48 , and  49 , wherein the second molecule is selected from the group consisting of poly(ethylene glycol) dithiol, 4arm-PEG2K-SH, 4arm-PEG5K-SH, 4arm-PEG10K-SH, 4arm-PEG20K-SH, 4-arm poly(ethylene oxide) thiol-terminated, 8arm-PEG10K-SH (hexaglyerol core), 8arm-PEG10K-SH (tripentaerythritol core), 8arm-PEG20K-SH (hexaglyerol core), 8arm-PEG20K-SH (tripentaerythritol core), and 8-arm poly(ethylene oxide) thiol-terminated. 
     
     
         52 . The method according to any one of  claims 24 - 46 ,  48 , and  49 , wherein the second molecule is a peptide having a disulfide bond or a protein having a disulfide bond. 
     
     
         53 . The method according to  claim 52 , wherein the second molecule is a protein having a disulfide bond selected from the group consisting of an SOD1 variant, a DJ-1 variant, an effector caspae, and IscU. 
     
     
         54 . The method according to  claim 53 , wherein the second molecule is a fALS-SOD1 variant. 
     
     
         55 . A composition, wherein the composition comprises a substrate and a coating material, wherein the coating material comprises a first monolayer comprising a plurality of moieties of Formula I 
       
         
           
           
               
               
           
         
         wherein 
         W is independently selected from the group consisting of S and Se; 
         Y is independently selected from the group consisting of S, Se, S(O), Se(O), S(O) 2  and Se(O) 2 ; and 
         X together with W and Y forms a substituted or unsubstituted 3-10-membered heterocyclic ring; and 
         the coating material is covalently bonded to the substrate. 
       
     
     
         56 . The composition according to  claim 55 , wherein the coating material comprises a first bilayer comprising a polymer derived from the moieties of Formula I and a plurality of first monomers comprising at least one thiol functional group, wherein a plurality of covalent bonds are formed between the S or Se atoms of the plurality of moieties and the free thiol groups of the first monomer. 
     
     
         57 . The composition according to  claim 56 , wherein the coating material comprises a second monolayer comprising a reduced form of the plurality of moieties of Formula I. 
     
     
         58 . The composition according to  claim 57 , wherein the coating material comprises a second bilayer comprising a plurality of metal-chelating groups of the second monolayer chelated to a plurality of metal ions. 
     
     
         59 . The composition according to  claim 58 , wherein the plurality of metal-chelating groups are S atoms. 
     
     
         60 . The composition according to  claim 58 , wherein the plurality of metal-chelating groups are Se atoms. 
     
     
         61 . The composition according to any one of  claims 58 - 60 , wherein the plurality of metal ions are a plurality of metal cations. 
     
     
         62 . The composition according to  claim 61 , wherein the metal cation has a charge of +1. 
     
     
         63 . The composition according to  claim 62 , wherein the metal cation is a cation of Ag or Au. 
     
     
         64 . The composition according to  claim 61 , wherein the metal cation has a charge of +2. 
     
     
         65 . The composition according to  claim 64 , wherein the metal cation is a cation of Ca, Cd, Co, Cr, Cu, Er, Fe, Hg, Mg, Mn, Nb, Ni, Pb, Pd, Sc, Sn, Sr, V, or Zn. 
     
     
         66 . The composition according to  claim 61 , wherein the metal cation has a charge of +3. 
     
     
         67 . The composition according to  claim 66 , wherein the metal cation is a cation of Au, Ce, Dy, Er, Eu, Fe, Gd, Ho, La, Lu, Nb, Nd, Pm, Pr, Sm, Tb, Tm, or Yb. 
     
     
         68 . The composition according to any one of  claims 58 - 67 , wherein the coating material comprises a trilayer further comprising a plurality of third molecules chelated to the plurality of metal ions, wherein the third molecules comprise a moiety of Formula I: 
       
         
           
           
               
               
           
         
         wherein 
         W is independently selected from the group consisting of S and Se; 
         Y is independently selected from the group consisting of S, Se, S(O), Se(O), S(O) 2  and Se(O) 2 ; and 
         X together with W and Y forms a substituted or unsubstituted 3-10-membered heterocyclic ring. 
       
     
     
         69 . The composition according to any one of  claims 55 - 68 , wherein the first monolayer comprises a plurality of moieties selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         70 . A method for transporting a molecule of interest across a cell membrane comprising:
 (a) providing a functionalized molecule of interest comprising a moiety of Formula I:   
       
         
           
           
               
               
           
         
         
           wherein 
           W is independently selected from the group consisting of S and Se; 
           Y is independently selected from the group consisting of S, Se, S(O), Se(O), S(O) 2  and Se(O) 2 ; and 
           X together with W and Y forms a substituted or unsubstituted 3-10-membered heterocyclic ring; and 
         
         (b) contacting a cell of interest with the functionalized molecule of interest under conditions for the moiety of Formula I to reversibly bind to one or more cell membrane transport proteins, 
         thereby facilitating transport of the molecule of interest across the cell membrane. 
       
     
     
         71 . The method according to  claim 70 , wherein the functionalized molecule comprises a moiety of Formula I selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         72 . A method for treating a keratin-containing material, comprising:
 i) providing a plurality of first monomers, wherein the first monomer is a keratin-containing material sample comprising a plurality of disulfide bonds;   ii) applying to the keratin-containing material sample for a period of time a mixture, comprising a reducing agent in a concentration of about 0.1% by weight to about 15% by weight, thereby producing a reduced keratin-containing material sample, wherein the reduced keratin-containing material sample comprises a plurality of free thiol groups; and   iii) applying a first cross-linker to the reduced keratin-containing material sample, wherein the first cross-linker comprises a moiety of Formula I:   
       
         
           
           
               
               
           
         
         wherein 
         W is independently selected from the group consisting of S and Se; 
         Y is independently selected from the group consisting of S, Se, S(O), Se(O), S(O) 2  and Se(O) 2 ; and 
         X together with Wand Y forms a substituted or unsubstituted 3-10-membered heterocyclic ring, 
         thereby forming a plurality of covalent bonds between the free thiol groups and the first cross-linkers. 
       
     
     
         73 . The method of  claim 72 , wherein the reducing agent is selected from the group consisting of ammonium thioglycolate, L-cysteine, glutathione, ascorbic acid, beta-mercaptoethanol, 2-mercaptoethylamine, 2-mercaptoethylamine hydrochloride, dithiothreitol (DTT), thiolactic acid, thiosalicylic acid, tris-2-carboxyethylphospine hydrochloride (TCEP), sodium hydrosulfite, sodium thiosulfate, potassium disulfite, sodium disulfite, sodium bisulfate, sodium bisulfite, ammonium bisulfite, thioglycolic acid, calcium thioglycolate, potassium thioglycolate, sodium thioglycolate, cysteine hydrochloride, ammonium thiolactate, thioglycerin, mercaptoprpionic acid, glycerol thioglycolate and dithiolbutylamine (DTBA). 
     
     
         74 . A method for treating a keratin-containing material, comprising:
 i) providing a plurality of first monomers, wherein the first monomer is a keratin-containing material sample comprising a plurality of disulfide bonds;   ii) applying to the keratin-containing material sample for a period of time a mixture, comprising a first cross-linker, wherein the first cross-linker comprises a moiety of Formula I:   
       
         
           
           
               
               
           
         
         wherein 
         W is independently selected from the group consisting of S and Se; 
         Y is independently selected from the group consisting of S, Se, S(O), Se(O), S(O) 2  and Se(O) 2 ; and 
         X together with W and Y forms a substituted or unsubstituted 3-10-membered heterocyclic ring, 
         thereby forming a plurality of free thiol groups which react with the first cross-linkers to form a plurality of covalent bonds between the free thiol groups and the first cross-linkers. 
       
     
     
         75 . The method of any one of  claims 72 - 74 , wherein the keratin-containing material is selected from the group consisting of hair, eyebrows, eyelashes, fingernails and toenails. 
     
     
         76 . The method of any one of  claims 72 - 74 , wherein the keratin-containing material is hair.