Antimicrobial poly(methacrylamide) derivatives prepared via aqueous RAFT polymerization exhibit biocidal efficiency dependent upon cation structure.
Antimicrobial peptides (AMPs) show great potential as alternative therapeutic agents to conventional antibiotics as they can selectively bind and eliminate pathogenic bacteria without harming eukaryotic cells. It is of interest to develop synthetic macromolecules that mimic AMPs behavior, but that can be produced more economically at commercial scale. Herein, we describe the use of aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare primary and tertiary amine-containing polymers with precise molecular weight control and narrow molecular weight distributions. Specifically, N-(3-aminopropyl)methacrylamide (APMA) was statistically copolymerized with N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) or N-[3-(diethylamino)propyl]methacrylamide (DEAPMA) to afford a range of (co)polymer compositions. Analysis of antimicrobial activity against  E. coli  (Gram-negative) and  B. subtilis  (Gram-positive) as a function of buffer type, salt concentration, pH, and time indicated that polymers containing large fractions of primary amine were most effective against both strains of bacteria. Under physiological pH and salt conditions, the polymer with the highest primary amine content caused complete inhibition of bacterial growth at low concentrations, while negligible hemolysis was observed over the full range of concentrations tested, indicating exceptional selectivity. The cytotoxicity of select polymers was evaluated against MCF-7 cells.
School of Polymers and High Performance Materials, The University of Southern Mississippi, Hattiesburg, Mississippi 39406-5050, United States.
Lea C
LC
Paslay
Brooks A
BA
Abel
Tyler D
TD
Brown
Veena
V
Koul
Veena
V
Choudhary
Charles L
CL
McCormick
Sarah E
SE
Morgan
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001412:Bacillus subtilis / Q000187:drug effects; D002412:Cations; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D052978:Disk Diffusion Antimicrobial Tests; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008970:Molecular Weight; D058105:Polymerization; D011109:Polymethacrylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D000900:Anti-Bacterial Agents; D002412:Cations; D011109:Polymethacrylic Acids