Antimicrobial polycarbonates for multidrug resistant bacteria

Abstract

Compositions and methods regarding guanidinium functionalized polycarbonates that provide potent antimicrobial activity against multidrug resistant (MDR) bacteria, including Klebsiella pneumoniae (K. pneumoniae) are provided. According to an embodiment, an antimicrobial guanidinium-functionalized polymer is provided that comprises a hydrophobic molecular backbone with cationic guanidinium moieties respectively bound to the hydrophobic molecular backbone via butyl spacer groups. The antimicrobial guanidinium-functionalized polymer self-assembles into a micelle structure with hydrophobic residuals of the antimicrobial guanidinium-functionalized polymer buried inside the micelle structure and the cationic guanidinium moieties exposed on an external surface of the micelle structure to target pathogens.

What is claimed is: 
     
         1 . A polymer having a form of a micelle structure, the polymer comprising:
 a molecular backbone structure with cationic guanidinium moieties respectively bound to the molecular backbone structure via butyl spacer groups, wherein the molecular backbone is buried inside the micelle structure and the cationic guanidium moieties are exposed on an external surface of the micelle structure.   
     
     
         2 . The polymer of  claim 1 , wherein the molecular backbone structure comprises polycarbonate. 
     
     
         3 . The polymer of  claim 1 , wherein the micelle structure has a size between 20 and 300 nanometers. 
     
     
         4 . The polymer of  claim 1 , wherein the polymer self-assembles into the micelle structure in aqueous solution with a critical micelle concentration below 500 mg/L. 
     
     
         5 . The polymer of  claim 1 , wherein the micelle structure mitigates exposure of the molecular backbone to mammalian cells. 
     
     
         6 . The polymer of  claim 1 , wherein the polymer exhibits antimicrobial activity towards Gram-negative bacteria and Gram-positive bacteria. 
     
     
         7 . The polymer of  claim 1 , wherein the polymer is effective at killing multidrug resistant strains of  Klebsiella pneumonia.    
     
     
         8 . The polymer of  claim 1 , wherein the polymer exhibits antimicrobial activity towards at least one bacteria selected from the group consisting of  Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus , methicillin-resistant  Staphylococcus aureus, Pseudomonas aeruginosa  and  Enterococcus faecium.    
     
     
         9 . The polymer of  claim 1 , wherein the molecular backbone is hydrophobic and comprises hydrophobic residuals buried inside the micelle structure. 
     
     
         10 . The polymer of  claim 1 , wherein the polymer has a chemical structure characterized by a structure selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein “n” represents an integer between 5 and 65, and 
         wherein “Me” represents a methyl group. 
       
     
     
         11 . A method, comprising:
 forming an intermediate polymer via a ring-opening polymerization of guanidinium-functionalized cyclic monomers in the presence of an initiator and an organo-catalyst; and   deprotecting a guanidinium moiety of the intermediate polymer using a protic acid, wherein the deprotecting forms an antimicrobial polymer having a cationic moiety bound to a molecular backbone via a butyl group, wherein the antimicrobial polymer self-assembles into a micelle structure in aqueous solution such that the molecular backbone is buried inside the micelle structure and the cationic guanidium moieties are exposed on an external surface of the micelle structure.   
     
     
         12 . The method of  claim 11 , wherein the initiator is a nucleophile comprising an alcohol group. 
     
     
         13 . The method of  claim 12 , wherein the organo-catalyst comprises at least one member selected from the group consisting of 1,8-Diazabicyclo[5,4,0]-undec-7-ene and N-(3,5 trifluoromethyl)phenyl-N-cyclohexylthiourea. 
     
     
         14 . The method of  claim 13 , wherein the protic acid is trifluoroacetic acid. 
     
     
         15 . The method of  claim 11 , wherein a ratio of an amount of the organo-catalyst to an amount of the guanidinium-functionalized cyclic monomers is at least 1:10. 
     
     
         16 . A method, comprising:
 synthesizing, via a ring opening polymerization, an antimicrobial polymer having a form of a micelle structure by mixing guanidinium-functionalized cyclic monomers with an initiator in the presence of an organo-catalyst, wherein the antimicrobial polymer comprises a hydrophobic molecular backbone structure with cationic guanidinium moieties respectively bound to the hydrophobic molecular backbone structure via butyl spacer groups, and wherein hydrophobic residuals of the antimicrobial polymer are buried inside the micelle structure and the cationic guanidinium moieties are exposed on an external surface of the micelle structure.   
     
     
         17 . The method of  claim 16 , wherein the initiator is a nucleophile comprising an alcohol group. 
     
     
         18 . The method of  claim 17 , wherein the organo-catalyst comprises at least one member selected from the group consisting of 1,8-Diazabicyclo[5,4,0]-undec-7-ene and N-(3,5 trifluoromethyl)phenyl-N-cyclohexylthiourea. 
     
     
         19 . The method of  claim 16 , wherein the mixing further comprises mixing the guanidinium-functionalized cyclic monomers with the initiator in the presence of the organo-catalyst and a protic acid. 
     
     
         20 . The method of  claim 16 , wherein a ratio of an amount of the organo-catalyst to an amount of the guanidinium-functionalized cyclic monomers is at least 1:10.