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The Role of Hydrophobicity in the Antimicrobial and Hemolytic Activities of Polymethacrylate Derivatives
Author(s) -
Kuroda Kenichi,
Caputo Gregory A.,
DeGrado William F.
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200801523
Subject(s) - polymer , cationic polymerization , chemistry , amphiphile , membrane , monomer , hydrophobic effect , copolymer , polymer chemistry , side chain , alkyl , methacrylate , organic chemistry , biochemistry
We synthesized cationic random amphiphilic copolymers by radical copolymerization of methacrylate monomers with cationic or hydrophobic groups and evaluated their antimicrobial and hemolytic activities. The nature of the hydrophobic groups, and polymer composition and length were systematically varied to investigate how structural parameters affect polymer activity. This allowed us to obtain the optimal composition of polymers suitable to act as non‐toxic antimicrobials as well as non‐selective polymeric biocides. The antimicrobial activity depends sigmoidally on the mole fraction of hydrophobic groups ( f HB ). The hemolytic activity increases as f HB increases and levels off at high values of f HB , especially for the high‐molecular‐weight polymers. Plots of HC 50 values versus the number of hydrophobic side chains in a polymer chain for each polymer series showed a good correlation and linear relationship in the log–log plots. We also developed a theoretical model to analyze the hemolytic activity of polymers and demonstrated that the hemolytic activity can be described as a balance of membrane binding of polymers through partitioning of hydrophobic side chains into lipid layers and the hydrophobic collapsing of polymer chains. The study on the membrane binding of dye‐labeled polymers to large, unilamellar vesicles showed that the hydrophobicity of polymers enhances their binding to lipid bilayers and induces collapse of the polymer chain in solution, reducing the apparent affinity of polymers for the membranes.