Quaternary phosphonium coated surfaces and methods of making the same

Abstract

Disclosed herein is a composition comprising a substrate with functionalized surface covalently bound to an anti-infective agent, such as a quaternary phosphonium compound with anti-bacterial activity against a broad range of bacteria, methods of synthesizing an anti-infective composition, and its resultant antimicrobial performance.

What is claimed is: 
     
         1 . A composition comprising
 a substrate comprising a functionalized surface; and   a quaternary phosphonium compound bonded to the functionalized surface, wherein the quaternary phosphonium compound has a radical of formula I   
       
         
           
           
               
               
           
         
         wherein X 1 , X 2 , X 3 , and X 4  are independently non-existent or independently selected from O, S, NR 5 , ═N—, PR 6 , and ═P—; and 
         wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6  are independently selected from the group consisting of hydrogen, alkyls, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, alkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, heteroalkyl, haloalkoxy, aryl, substituted aryl, aryloxy, aralkyloxy, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, amino, alkylamino, dialkylamino, hydroxyalkylamino, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl), carboxamido, (carboxamido)alkyl, methacrylate, methacrylamide, sulfonamide, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, mercaptoalkyl, carboxy, carboxyalkyl, ureido, guanidine, (heterocyclo)alkyl, (heteroaryl)alkyl. 
       
     
     
         2 . The composition of  claim 1 , wherein the functionalized surface is natively functionalized or functionalized with a functionalizing agent covalently bonded thereto. 
     
     
         3 . The composition of  claim 2 , further comprising a linker, having a proximal end and a distal end, wherein the linker is covalently bonded on its proximal end to the natively functionalized surface, and wherein the linker is covalently bonded on its distal end to the quaternary phosphonium compound. 
     
     
         4 . The composition of  claim 2 , further comprising a linker, having a proximal and a distal end, wherein the linker is covalently bonded on its proximal end to the functionalizing agent, and wherein the linker is covalently bonded on its distal end to the quaternary phosphonium compound. 
     
     
         5 . The composition of  claim 1 , wherein the functionalized surface is selected from the group consisting of metals, alloys, polymers, plastics, ceramics, silicon, glass, composites, tissue and surfaces with acidic protons. 
     
     
         6 . The composition of  claim 2 , wherein the functionalized surface is functionalized with a functionalizing agent selected from the group consisting of phosphonic acids, phosphoric acids, carboxylic acids, sulfonic acids, sulfinic acids, phosphonates, phosphonic acid anhydrides, phosphoric acid esters, phosphorus pentoxides, carboxylic acid esters, carboxylic anhydrides, sulfonates, sulfonic acid anhydrides, sulfinic esters, sulfinic anhydrides, alcohols, thiols, alkanes, alkenes, alkynes, and diazo compounds. 
     
     
         7 . The composition of  claim 1 , wherein the quaternary phosphonium compound has a structure 
       
         
           
           
               
               
           
         
       
       wherein n2 is between 1 and 50. 
     
     
         8 . The composition of  claim 4 , wherein the linker has a structure 
       
         
           
           
               
               
           
         
         wherein n1 is between 1 and 100 and R′ is independently a hydrogen, or a quaternary phosphonium compound. 
       
     
     
         9 . The composition of  claim 4  having a structure 
       
         
           
           
               
               
           
         
       
       wherein n1 is between 1 and 100. 
     
     
         10 . A method for preparing a composition comprising
 attaching a quaternary phosphonium compound to a functionalized surface of a substrate, wherein the quaternary phosphonium compound has a radical of formula I   
       
         
           
           
               
               
           
         
         wherein X 1 , X 2 , X 3 , and X 4  are independently non-existent or independently selected from O, S, NR 5 , ═N—, PR 6 , and ═P—; and 
         wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6  are independently selected from the group consisting of hydrogen, alkyls, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, alkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, haloalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, heteroalkyl, haloalkoxy, aryl, substituted aryl, aryloxy, aralkyloxy, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, amino, alkylamino, dialkylamino, hydroxyalkylamino, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (cyano)alkyl), carboxamido, (carboxamido)alkyl, methacrylate, methacrylamide, sulfonamide, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, mercaptoalkyl, carboxy, carboxyalkyl, ureido, guanidine, (heterocyclo)alkyl, and (heteroaryl)alkyl, and are linked to the phosphorus through any one of oxygen, nitrogen, sulfur, carbon, and phosphorus. 
       
     
     
         11 . The method of  claim 10 , wherein attaching the quaternary phosphonium compound to a functionalized surface comprises
 covalently bonding a functionalizing agent to the surface; and   covalently bonding the quaternary phosphonium compound to the functionalized surface.   
     
     
         12 . The method of  claim 10 , wherein attaching a quaternary phosphonium compound to a functionalized surface comprises
 covalently binding a functionalizing agent to the surface;   activating the surface;   polymerizing a linker, having a proximal and a distal end, to form a covalent bond between the activated functionalized surface and the proximal end of the linker; and   subsequently covalently binding the distal end of the linker to the quaternary phosphonium compound.   
     
     
         13 . The method of  claim 10 , wherein attaching a quaternary phosphonium compound to a functionalized surface comprises
 polymerizing a linker, having a proximal and a distal end, to form a covalent bond between the quaternary phosphonium compound and the distal end of the linker; and   subsequently covalently binding the proximal end of the linker to the functionalized surface.   
     
     
         14 . The method of  claim 10 , wherein the functionalized surface is selected from the group consisting of metals, alloys, polymers, plastics, ceramics, silicon, glass, composites, tissue and surfaces with acidic protons. 
     
     
         15 . The method of  claim 11 , wherein the functionalizing agent is selected from the group consisting of phosphonic acids, phosphoric acids, carboxylic acids, sulfonic acids, sulfinic acids, phosphonates, phosphonic acid anhydrides, phosphoric acid esters, phosphorus pentoxides, carboxylic acid esters, carboxylic anhydrides, sulfonates, sulfonic acid anhydrides, sulfinic esters, sulfinic anhydrides, alcohols, thiols, alkanes, alkenes, alkynes, and diazo compounds. 
     
     
         16 . The method of  claim 10 , wherein the quaternary phosphonium compound is a radical of 
       
         
           
           
               
               
           
         
       
       wherein n2 is between 1 and 50. 
     
     
         17 . The method of  claim 13 , wherein the linker has a structure 
       
         
           
           
               
               
           
         
         wherein n1 is between 1 and 100 and R′ is independently a hydrogen, or a quaternary phosphonium compound. 
       
     
     
         18 . The method of  claim 12 , wherein the composition has a structure 
       
         
           
           
               
               
           
         
       
       wherein n1 is between 1 and 100. 
     
     
         19 . The composition of  claim 1 , wherein the quaternary phosphonium compound is a radical of 
       
         
           
           
               
               
           
         
       
       wherein n3 is between 1 and 50. 
     
     
         20 . The method of  claim 10 , wherein the quaternary phosphonium compound is a radical of 
       
         
           
           
               
               
           
         
       
       wherein n3 is between 1 and 50.