N-halamine vinyl compounds and their polymeric biocides

Abstract

The present invention provides heterocyclic vinylic compounds that can be used to form biocidal polymers. The polymers thus generated can be used alone or can be grafted onto textiles, fabrics and polymers. The polymers are readily converted to N-halamine structures on exposure to a halogen source such as commercially available chlorine bleach. The N-halamine derivatives exhibit potent antibacterial properties against microorganisms and these properties are durable and regenerable.

1 . A polymer comprising a mixture of monomeric units having the formulae:  
     
       
         
         
             
             
         
       
     
     wherein: 
 A is a member selected from the group consisting of NH, N—R 8  and CR 1 R 2 , wherein R 8  is a halogen;  
 R 1  and R 2 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;  
 or, R 1  and R 2  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;  
 Q is a member selected from the group consisting of C(O), NH, N—R 9  and CR 3 R 4 , wherein R 9  is a halogen;  
 R 3  and R 4 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;  
 or, R 3  and R 4  and the carbon to which they are bound, join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring.  
 X is a member selected from the group consisting of C(O)—NR 10  and CR 6 R 7 , wherein R 10  is a member selected from the group consisting of hydrogen, halogen, optionally substituted (C 2 -C 6 )alkenyl and optionally substituted (C 1 -C 6 )alkyl;  
 R 6  and R 7 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;  
 or, R 6  and R 7  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;  
 Z is a member selected from the group consisting of optionally substituted (C 1 -C 3 )alkylene, C(O), or a single bond;  
 R 11  is a member selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylcarbonyl, (C 1 -C 6 )alkylcarboxyl, aldehydo, amido, aryl and heterocyclyl;  
 R 12  is a member selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylcarbonyl, (C 1 -C 6 )alkylcarboxyl, aldehydo, amido, aryl and heterocyclyl;  
 R 13  is a member selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylcarbonyl, (C 1 -C 6 )alkylcarboxyl, aldehydo, amido, aryl and heterocyclyl;  
 R 14  is a member selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylcarbonyl, (C 1 -C 6 )alkylcarboxyl, aldehydo, amido, aryl and heterocyclyl; and  
 n and y are each independently an integer from 1 to 250 inclusive.  
 
   
   
       2 . The polymer of  claim 1 , wherein: A is NH and Z is CH 2 .  
   
   
       3 . The polymer of  claim 1 , wherein: A is CR 1 R 2 , wherein R 1  and R 2 , are each optionally substituted (C 1 -C 6 )alkyl.  
   
   
       4 . The polymer of  claim 3 , wherein: R 1  and R 2 , are each (C 1 -C 3 )alkyl.  
   
   
       5 . The polymer of  claim 1 , wherein: A is CR 1 R 2 , and wherein R 1  and R 2  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring.  
   
   
       6 . The polymer of  claim 5 , wherein: R 1  and R 2  and the carbon to which they are bound join to form an optionally substituted carbocyclic ring.  
   
   
       7 . The polymer of  claim 1 , wherein: Q is C(O).  
   
   
       8 . The polymer of  claim 1 , wherein: Q is NH.  
   
   
       9 . The polymer of  claim 1 , wherein: Q is CR 3 R 4 , wherein R 3  and R 4 , are each optionally substituted (C 1 -C 6 )alkyl.  
   
   
       10 . The polymer of  claim 1 , wherein: X is CR 6 R 7 , wherein R 6  and R 7 , are each optionally substituted (C 1 -C 6 )alkyl.  
   
   
       11 . The polymer of  claim 1 , wherein: X is C(O)NH.  
   
   
       12 . The polymer of  claim 1 , wherein said polymer is a film.  
   
   
       13 . A textile material comprising a polymer of  claim 1 .  
   
   
       14 . A method for making a polymer, said method comprising: admixing a compound having the formula:  
     
       
         
         
             
             
         
       
     
     wherein: 
 A is a member selected from the group consisting of NH, N—R 8  and CR 1 R 2 , wherein R 8  is a halogen;  
 R 1  and R 2 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;  
 or, R 1  and R 2  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;  
 Q is a member selected from the group consisting of C(O), NH, N—R 9  and CR 3 R 4 , wherein R 9  is a halogen;  
 R 3  and R 4 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;  
 or, R 3  and R 4  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;  
 X is a member selected from the group consisting of C(O), C(O)—NR 5  and CR 6 R 7 , wherein R 5  is a member selected from the group consisting of hydrogen, halogen, optionally substituted (C 2 -C 6 )alkenyl and optionally substituted (C 1 -C 6 )alkyl;  
 R 6  and R 7 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;  
 or, R 6  and R 7  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; and  
 Z is a member selected from the group consisting of optionally substituted (C 1 -C 3 )alkylene, C(O), or a single bond,  
 with a vinyl monomer in a reaction mixture thereby making said polymer.  
 
   
   
       15 . The method of  claim 14 , wherein said vinyl monomer is a member selected from the group consisting of an acrylic monomer, a monofunctional vinyl monomer, a polyfunctional vinyl monomer and mixtures thereof.  
   
   
       16 . The method of  claim 14 , wherein said reaction mixture further comprises a free radical initiator.  
   
   
       17 . The method of  claim 14 , wherein said vinyl monomer is selected from the group consisting of acrylonitrile, methacrylate, vinyl acetate and mixtures thereof.  
   
   
       18 . The method of  claim 14 , further comprising treating said polymer with a halogenated aqueous solution.  
   
   
       19 . A polymer comprising a monomeric unit having the formula:  
     
       
         
         
             
             
         
       
     
     wherein: 
 A is a member selected from the group consisting of NH, N—R 8  and CR 1 R 2 , wherein R 8  is a halogen;  
 R 1  and R 2 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;  
 or, R 1  and R 2  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;  
 Q is a member selected from the group consisting of C(O), NH, N—R 9  and CR 3 R 4 , wherein R 9  is a halogen;  
 R 3  and R 4 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;  
 or, R 3  and R 4  and the carbon to which they are bound, join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring.  
 X is a member selected from the group consisting of C(O)—NR 10  and CR 6 R 7 , wherein R 10  is a member selected from the group consisting of hydrogen, halogen, optionally substituted (C 2 -C 6 )alkenyl and optionally substituted (C 1 -C 6 )alkyl;  
 R 6  and R 7 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;  
 or, R 6  and R 7  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;  
 Z is a member selected from the group consisting of optionally substituted (C 1 -C 3 )alkylene, C(O), or a single bond; and  
 n is an integer from 1 to 250 inclusive.  
 
   
   
       20 . A method for making a polyethylene derivative antimicrobial polymer comprising: 
 polymerizing a mixture comprising: 
 (a) an ethylene derivative of the formula:  
   R 11 R 12 C═CR 13 R 14    
 and  
 (b) a compound of the formula:  
                     
 to produce a polyethylene derivative antimicrobial polymer,  
 wherein  
   A is a member selected from the group consisting of NH, N—R and CR 1 R 2 , wherein R 8  is a halogen;    R 1  and R 2 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;    or, R 1  and R 2  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;    Q is a member selected from the group consisting of C(O), NH, N—R 9  and CR 3 R 4 , wherein R 9  is a halogen;    R 3  and R 4 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;    or, R 3  and R 4  and the carbon to which they are bound, join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring.    X is a member selected from the group consisting of C(O)—NR 10  and CR 6 R 7 , wherein R 10  is a member selected from the group consisting of hydrogen, halogen, optionally substituted (C 2 -C 6 )alkenyl and optionally substituted (C 1 -C 6 )alkyl;    R 6  and R 7 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;    or, R 6  and R 7  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;    Z is a member selected from the group consisting of optionally substituted (C 1 -C 3 )alkylene, C(O), or a single bond;    R 11  is a member selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylcarbonyl, (C 1 -C 6 )alkylcarboxyl, aldehydo, amido, aryl and heterocyclyl;    R 12  is a member selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylcarbonyl, (C 1 -C 6 )alkylcarboxyl, aldehydo, amido, aryl and heterocyclyl;    R 13  is a member selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylcarbonyl, (C 1 -C 6 )alkylcarboxyl, aldehydo, amido, aryl and heterocyclyl;    R 14  is a member selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylcarbonyl, (C 1 -C6)alkylcarboxyl, aldehydo, amido, aryl and heterocyclyl; and    n and y are each independently an integer from 1 to 250 inclusive.    
   
   
       21 . A method for making an antimicrobial polymer, said method comprising: 
 contacting a polymer with a compound of the formula:                          under conditions sufficient to covalently attach the compound of Formula I to the polymer to produce an antimicrobial polymer,    wherein    A is a member selected from the group consisting of NH, N—R 8  and CR 1 R 2 , wherein R 8  is a halogen;    R 1  and R 2 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;    or, R 1  and R 2  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;    Q is a member selected from the group consisting of C(O), NH, N—R 9  and CR 3 R 4 , wherein R 9  is a halogen;    R 3  and R 4 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;    or, R 3  and R 4  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;    X is a member selected from the group consisting of C(O), C(O)—NR 5  and CR 6 R 7 , wherein R 5  is a member selected from the group consisting of hydrogen, halogen, optionally substituted (C 2 -C 6 )alkenyl and optionally substituted (C 1 -C 6 )alkyl;    R 6 and R 7 , are each independently selected from the group consisting of optionally substituted (C 1 -C 6 )alkyl, optionally substituted (C 2 -C 6 )alkenyl, optionally substituted (C 2 -C 6 )alkynyl, optionally substituted cycloalkyl, optionally substituted (C 1 -C 6 )alkoxy, optionally substituted aryl and optionally substituted heteroaryl;    or, R 6  and R 7  and the carbon to which they are bound join to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; and    Z is a member selected from the group consisting of optionally substituted (C 1 -C 3 )alkylene, C(O), or a single bond.    
   
   
       22 . The method of  claim 21 , wherein the polymer comprises an unsaturated carbon-carbon bond such that the compound of formula I is covalently attached to the polymer via a carbon-carbon linkage.  
   
   
       23 . The method of  claim 22 , wherein the carbon-carbon linkage is formed via free-radical reaction.