Disintegratable porous organometaloxide material

Abstract

The present invention relates to disintegratable mesoporous silica materials, a method for producing the same, and uses thereof.

1 . A disintegratable porous organometaloxide material comprising a porous three-dimensional framework of metal-oxygen bonds, wherein at least a subset of metal atoms in the material's framework are connected to at least another metal atom in the framework through a linker having one of the following structures: 
       
         
           
           
               
               
           
         
       
       wherein :
 each occurrence of * denotes a point of attachment to a metal atom in the material's framework; 
 A represents a monomer of a responsively cleavable fragment of biological/biodegradable polymer; 
 m is an integer from 2 to 10000 and m represents the number of monomers in the fragment of biological/biodegradable polymer; 
 L represents a responsively cleavable covalent bond, and 
 R 1  and R 2  independently represent an optionally substituted C 1-20 alkylenyl moiety, an optionally substituted C 1-20 heteroalkylenyl moiety, an optionally substituted ethylenyl moiety, —C≡C— or an optionally substituted phenyl moiety, wherein the C 1-20 alkylenyl, C 1-20 heteroalkylenyl or ethylenyl moiety may bear one or more substituents selected from halogen or —OR where R may represent H or C 1-6 alkyl, and the phenyl moiety may bear one or more substituents independently selected from halogen, C 1-6 alkyl, —NO 2 , —CN, isocyano, —OR P , —N(R P ) 2  wherein each occurrence of R P  independently represents H or C 1-6 alkyl; 
 wherein said disintegratable porous organometaloxide material has a particle diameter from about 1 nm to about 1000 nm. 
 
     
     
         2 . The material of  claim 1 , wherein the three-dimensional framework of metal-oxygen bonds is mesoporous, microporous, macroporous or mixed mesoporous-macroporous. 
     
     
         3 . The material of  claim 1 , wherein the linker has the structure —R 1 -L-R 2 —*, and L represents a responsively cleavable covalent bond selected from boronic acid derivatives, disulfide, diselenide, ester, amide, imine, acetal, ketal, anhydride, urea, thiourea, hydrazine or oxyme. 
     
     
         4 . The material of  claim 1 , wherein the linker represents a responsively cleavable fragment of biological/biodegradable polymer selected from carbohydrates, peptides and synthetic biodegradable polyethyleneglycol or polylactide polymers, and the linker has the structure 
       
         
           
           
               
               
           
         
       
       wherein A, m, R 1  and R 2  are as defined in  claim 1 . 
     
     
         5 . The material of  claim 1 , wherein the metal is selected from Si, Ti or Zr, or any combination of at least two of these metals. 
     
     
         6 . The material of  claim 1 , wherein the material contains 90.0-100% Si, 90.0-100% Ti or 90.0-100% Zr as metal, wherein the % are based on the number of available metal sites in the framework. 
     
     
         7 . The material of  claim 1 , wherein the material is a Si—Ti mixed-metal organometaloxide material containing 0.1-50.0% Si and 0.1-50.0% Ti, the % sum of Si and Ti adding to 100% the number of available metal sites in the framework. 
     
     
         8 . The material of  claim 1 , wherein in the linker represents *—R 1 -L-R 2 —*, R 1  and R 2  are identical, and each represent —CH 2 —, —(CH 2 ) 2 —, —(CH 2 ) 3 —, —(CH 2 ) 4 —, or phenyl. 
     
     
         9 . The material of  claim 1 , wherein the material is in the form of a monolith, a thin or thick film, a powder, nanoparticles, or spherical, cubic, cylindrical or disc-like particles. 
     
     
         10 . The material of  claim 1 , said material comprising in its pores or at its surface at least one marker and/or cosmetically or pharmaceutically active principle. 
     
     
         11 . The material of  claim 10 , wherein the marker is selected from a contrast agent, a tracer, a radioactive marker, a fluorescent marker, a phosphorescent marker, a magnetic resonance imaging agent or a positron emission tomography agent. 
     
     
         12 . Method for treating a condition or disease comprising administering to a subject in need thereof a disintegratable porous organometaloxide material according to  claim 1 , appropriately loaded on its surface or in its pore with at least one pharmaceutically active principle adapted for such treatment. 
     
     
         13 . A pharmaceutical, cosmetic, catalytic, paint, ink, photovoltaic or optical coating composition comprising the material of  claim 1 . 
     
     
         14 . A method for preparing a material of  claim 1 , comprising steps of:
 a) Producing a supramolecular template by mixing a suitable surfactant and an aqueous solvent;   b) Adding a mixture of a precursor M(X A ) 4  and a selected precursor having the structure:   
       
         
           
           
               
               
           
         
         in an aqueous solvent under alkaline conditions; thereby coating the supramolecular template with an organometaloxide sol-gel mixture obtained by hydrolysis-condensation of metal alkoxide; and 
         c) Removing the supramolecular template; thereby producing a porous organometaloxide nanoparticles comprising a porous three-dimensional framework of metal-oxygen bonds, wherein at least a subset of metal atoms in the material's framework are connected to at least another metal atom in the framework through a linker having one of the following structures: 
       
       
         
           
           
               
               
           
         
         wherein:
 each occurrence of * denotes a point of attachment to a metal atom in the material's framework; 
 
         A represents a monomer of a responsively cleavable fragment of biological/biodegradable polymer; 
         m is an integer from 2 to 10000 and m represents the number of monomers in the fragment of biological/biodegradable polymer; 
         M and each occurrence of M 1  and M 2  independently represents a metal selected from Si, Ti and Zr; 
         each occurrence of X and X A  independently represents a hydrolysable or nonhydrolyzable group, provided that on each occurrence of M 1  and M 2 , at least one occurrence of X represents a hydrolysable group and at least two occurrences of X A  in the precursor M(X A ) 4  independently represent a hydrolysable group; wherein (i) when X or X A  represents a nonhydrolyzable group, it may be selected from an optionally substituted C 1-20 alkyl, C 2-20 alkenyl or C 2-20 alkynyl moiety, an optionally substituted C 1-20 heteroalkyl, C 2-20 heteroalkynyl or C 2-20 heteroalkynyl moiety, or an optionally substituted phenyl moiety, wherein the substituents on the phenyl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl and heteroalkynyl moieties may be independently selected from halogen, —NO 2 , —CN, isocyano, C 1-6 alkoxy, an oxirane/epoxyde moiety, —N(R) 2  wherein each occurrence of R is independently selected from H or C1-6alkyl; and (ii) when X or X A  represents a hydrolysable group, it may be selected from a C1-6alkoxy, C 1-6 acyloxy, halogen or amino moiety; 
         L represents a responsively cleavable covalent bond; and 
         R 1  and R 2  independently represent an optionally substituted C 1-20 alkylenyl moiety, an optionally substituted C 1-20 heteroalkylenyl moiety, an optionally substituted ethylenyl moiety, —C≡C— or an optionally substituted phenyl moiety, wherein the C 1-20 alkylenyl, C 1-20 heteroalkylenyl or ethylenyl moiety may bear one or more substituents selected from halogen or —OR where R may represent H or C 1-6 alkyl, and the phenyl moiety may bear one or more substituents independently selected from halogen, C 1-6 alkyl, —NO 2 , —CN, isocyano, —OR P , —N(R P ) 2  wherein each occurrence of R P  independently represents H or C1-6 alkyl. 
       
     
     
         15 . A method for preparing a material of  claim 1  being 100% doped, comprising steps of:
 a) Producing a supramolecular template by mixing a suitable surfactant and an aqueous solvent; 
 b) Adding a selected precursor having the structure: 
 
       
         
           
           
               
               
           
         
         
           in an aqueous solvent under alkaline conditions; thereby coating the supramolecular template with an organometaloxide sol-gel mixture obtained by hydrolysis-condensation of metal alkoxide; and 
         
         c) Removing the supramolecular template; thereby producing a porous organometaloxide material comprising a porous three-dimensional framework of metal-oxygen bonds, wherein at least a subset of metal atoms in the material's framework are connected to at least another metal atom in the framework through a linker having one of the following structures: 
       
       
         
           
           
               
               
           
         
         wherein:
 each occurrence of * denotes a point of attachment to a metal atom in the material's framework; 
 A represents a monomer of a responsively cleavable fragment of biological/biodegradable polymer; 
 m is an integer from 2 to 10000 and m represents the number of monomers in the fragment of biological/biodegradable polymer; 
 each occurrence of M 1  and M 2  independently represents a metal selected from Si, Ti and Zr; 
 each occurrence of X independently represents a hydrolysable or nonhydrolyzable group, provided that on each occurrence of M 1  and M 2 , at least one occurrence of X represents a hydrolysable group; wherein (i) when X represents a nonhydrolyzable group, it may be selected from an optionally substituted C 1-20  alkyl, C 2-20  alkenyl or C 2-20  alkynyl moiety, an optionally substituted C 1-20  heteroalkyl, C 2-20  heteroalkynyl or C 2-20  heteroalkynyl moiety, or an optionally substituted phenyl moiety, wherein the substituents on the phenyl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl and heteroalkynyl moieties may be independently selected from halogen, —NO 2 , —CN, isocyano, C 1-6  alkoxy, an oxirane/epoxyde moiety, —N(R) 2  wherein each occurrence of R is independently selected from H or C 1-6  alkyl; and (ii) when X represents a hydrolysable group, it may be selected from a C 1-6  alkoxy, C 1-6  acyloxy, halogen or amino moiety; 
 L represents a responsively cleavable covalent bond; and 
 R 1  and R 2  independently represent an optionally substituted C 1-20 alkylenyl moiety, an optionally substituted C 1-20 heteroalkylenyl moiety, an optionally substituted ethylenyl moiety, —C≡C— or an optionally substituted phenyl moiety, wherein the C 1-20 alkylenyl, C 1-20 heteroalkylenyl or ethylenyl moiety may bear one or more substituents selected from halogen or —OR where R may represent H or C 1-6 alkyl, and the phenyl moiety may bear one or more substituents independently selected from halogen, C 1-6 alkyl, —NO 2 , —CN, isocyano, —OR P , —N(R P ) 2  wherein each occurrence of R P  independently represents H or C 1-6 alkyl. 
 
       
     
     
         16 . The method of  claim 15 , wherein the metal is Si. 
     
     
         17 . The method of  claim 15 , wherein M(X A ) 4  represents a tetraalkoxysilane such as tetramethoxysilane, tetraethoxysilane and tetrapropoxysilane, preferably tetraethoxysilane (TEOS). 
     
     
         18 . The method of  claim 15 , wherein the surfactant is a cationic surfactant, an anionic surfactant, a non-ionic surfactant; preferably a cationic surfactant such as octadecyl trimethyl ammonium bromide, hexadecyl trimethyl ammonium bromide, tetradecyl trimethyl ammonium bromide, dodecyl trimethyl ammonium bromide, decyl trimethyl ammonium bromide, octyl trimethyl ammonium bromide, hexyl trimethyl ammonium bromide and other quaternary ammonium salt-type cationic surfactants. 
     
     
         19 . The method of  claim 15 , wherein the precursor having the structure (X) 3 M-R 1 -L-R 2 -M(X) 3  is produced in situ.