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Tuning the Hemolytic and Antibacterial Activities of Amphiphilic Polynorbornene Derivatives
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    Tuning the Hemolytic and Antibacterial Activities of Amphiphilic Polynorbornene Derivatives
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    Contribution from the Department of Polymer Science and Engineering and Department of Microbiology, University of Massachusetts Amherst, Amherst, Massachusetts 01003
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2004, 126, 48, 15870–15875
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    https://doi.org/10.1021/ja045664d
    Published November 13, 2004
    Copyright © 2004 American Chemical Society

    Abstract

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    Amphiphilic cationic polynorbornene derivatives, soluble in water, were prepared from modular norbornene monomers, with a wide range of molecular weights (Mn = 1600−137 500 g/mol) and narrow polydispersities (PDI = 1.1−1.3). The antibacterial activity determined by growth inhibition assays and the hemolytic activity against human red blood cells were measured and compared to determine the selectivity of the polymers for bacterial over mammalian cells. The effects of monomer repeat unit hydrophobicity and polymer molecular weight on antibacterial and hemolytic activities were determined. The hydrophobicity of the repeat unit was observed to have dramatic effects on antibacterial and hemolytic activities. Lipid membrane disruption activities of the polymers was confirmed by measuring polymer-induced dye leakage from large unilamellar vesicles. By tuning the overall hydrophobicity of the polymer through random copolymerizations of modular norbornene derivatives, highly selective, nonhemolytic antibacterial activities were obtained. For appropriate monomer composition, selectivity against bacteria versus human red blood cells was determined to be over 100.

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     Department of Polymer Science and Engineering.

     Department of Microbiology.

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    In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

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    Antibacterial and hemolytic activities of a Magainin derivative (MSI-78) as reference. Polymer concentration versus percent hemolysis curves. This material is available free of charge via the Internet at http://pubs.acs.org.

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    This article is cited by 438 publications.

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    Published November 13, 2004
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