Antimicrobial polymers formed by bulk polyaddition

Abstract

Cationic antimicrobial polymers have been synthesized by a bulk addition polymerization of a nucleophilic agent comprising two tertiary amines and an electrophilic agent that comprises two leaving groups and an aromatic ring between the leaving groups. The reaction solvent for the polymerization is chosen to allow precipitation of the cationic polymer at the polymerization temperature, thereby limiting molecular weight. Quaternization and polymerization occur concurrently. The cationic polymers can be highly active against Gram-negative and Gram-positive microbes, and/or fungi. The cationic polymers can also be non-hemolytic and non-cytotoxic at the effective concentration against the microbes.

1 . A cationic polymer comprising a cationic repeat unit of formula (C-5): 
       
         
           
           
               
               
           
         
       
       wherein
 each R′ is an independent monovalent radical selected from the group consisting of methyl, ethyl and propyl, and 
 each X′ is an independent negative-charged counterion. 
 
     
     
         2 . The cationic polymer of  claim 1 , wherein the cationic polymer is a homopolymer. 
     
     
         3 . The cationic polymer of  claim 1 , wherein each R′ is methyl. 
     
     
         4 . The cationic polymer of  claim 1 , wherein each X′ is chloride. 
     
     
         5 . The cationic polymer of  claim 1 , wherein the cationic polymer is an effective antimicrobial agent capable of killing a microbe selected from the group consisting of  Staphylococcus aureus  ( S. aureus ),  Escherichia coli  ( E. coli ),  Candida albicans  ( C. albicans ),  Pseudomonas aeruginosa  ( P. aeruginosa ),  Staphylococcus epidermidis  ( S. epidermidis ), Methicillin-resistant  Staphylococcus aureus  (MRSA), Vancomycin-resistant  Enterococcus  (VRE),  Acinetobacter baumannii  ( A. baumannii ),  Klebsiella pneumoniae  ( K. pneumoniae ),  Cryptococcus neoformans  ( C. neoformans ), and yeasts. 
     
     
         6 . The cationic polymer of  claim 1 , wherein the cationic polymer is a random copolymer comprising a second cationic repeat unit of formula (C-7): 
       
         
           
           
               
               
           
         
       
       wherein
 atomic centers nitrogen 1 and carbon 2 are labeled, 
 each X′ is an independent negative-charged counterion, 
 each R″ is an independent monovalent radical selected from the group consisting of methyl, ethyl and propyl. 
 
     
     
         7 . The cationic polymer of  claim 6 , wherein the cationic polymer comprises the cationic repeat units of formulas (C-5) and (C-7) in a (C-5):(C-7) molar ratio of 90:10 to 50:50. 
     
     
         8 . A method of killing a microbe, comprising contacting the microbe with the cationic polymer of  claim 1 . 
     
     
         9 . An antimicrobial composition, comprising the cationic polymer of  claim 1  and a second component bound together by non-covalent interactions. 
     
     
         10 . The antimicrobial composition of  claim 9 , wherein the second component is water. 
     
     
         11 . The antimicrobial composition of  claim 9 , wherein the second component is an antibiotic drug. 
     
     
         12 . The antimicrobial composition of  claim 9 , wherein the cationic polymer is a random copolymer comprising a second cationic repeat unit of formula (C-7): 
       
         
           
           
               
               
           
         
       
       wherein
 atomic centers nitrogen 1 and carbon 2 are labeled, 
 each X′ is an independent negative-charged counterion, 
 each R″ is an independent monovalent radical selected from the group consisting of methyl, ethyl and propyl. 
 
     
     
         13 . A cationic polymer, comprising a cationic repeat unit of formula (C-7): 
       
         
           
           
               
               
           
         
       
       wherein
 atomic centers nitrogen 1 and carbon 2 are labeled, 
 each X′ is an independent negative-charged counterion, 
 each R″ is an independent monovalent radical selected from the group consisting of methyl, ethyl and propyl. 
 
     
     
         14 . The cationic polymer of  claim 13 , wherein the cationic polymer is a homopolymer. 
     
     
         15 . The cationic polymer of  claim 13 , wherein the cationic polymer is a random copolymer comprising a second cationic repeat unit of formula (C-1): 
       
         
           
           
               
               
           
         
       
       wherein
 atomic centers nitrogen 1 and carbon 2 of formula (C-1) are labeled, 
 each X′ is an independent negative-charged counterion, and 
 each R′ of (C-1) is an independent monovalent radical selected from the group consisting of methyl, ethyl and propyl. 
 
     
     
         16 . The cationic polymer of  claim 13 , wherein the cationic polymer is a random copolymer comprising a second cationic repeat unit of formula (C-5): 
       
         
           
           
               
               
           
         
       
       wherein
 each R′ of (C-5) is an independent monovalent radical selected from the group consisting of methyl, ethyl and propyl, and 
 each X′ of (C-5) is an independent negative-charged counterion. 
 
     
     
         17 . A method of killing a microbe, comprising contacting the microbe with the cationic polymer of  claim 13 . 
     
     
         18 . An antimicrobial composition, comprising the cationic polymer of  claim 13  and a second component bound together by non-covalent interactions. 
     
     
         19 . The antimicrobial composition of  claim 18 , wherein the second component is water. 
     
     
         20 . The antimicrobial composition of  claim 18 , wherein the second component is an antibiotic drug.