Antimicrobial polymers

Abstract

Antimicrobial polymers are becoming increasingly popular as an alternative approach and solution to traditional antibiotics in the fight against pathogens. Polymers can be designed to target a wide range of pathogens, including both Gram-positive and Gram-negative bacteria, viruses, and fungi. Cationic polymers, in particular, have shown huge potential because of their mechanisms of action, notably their interactions with the various negatively charged cell envelope components of bacteria. This can lead to membrane disruption and ultimately bacterial death. These polymers can be synthesized directly from monomers, or existing polymers can be functionalized to give antimicrobial moieties, such as quaternary ammonium groups, to give an antimicrobial effect. In this thesis, the antimicrobial properties of polymers containing quaternary ammonium groups against a wide range of microorganisms both in solution and on surfaces were investigated. Thus, a small library of homopolymers, comprised of quaternary ammonium monomers, was synthesized through Reversible Addition Fragmentation Chain Transfer polymerization to give polymers with well-defined molecule weights. The polymerization reactions were optimized, and the antimicrobial activity of these polymers assessed against Gram-negative and two Gram-positive bacteria. A key objective was to examine the effect molecular weight had on the antimicrobial activity of the homopolymers. The most effective polymers were subjected to detailed investigation to assess their impact on bacteria, fungi, mammalian cells, and erythrocytes specifically analysing the effect of polymer molecular weights on their activity. The antimicrobial mechanisms of action of the polymers were iii examined in detail, and through this process, identified polymers that were non-toxic to mammalian cells, yet highly bactericidal. In a complementary research endeavor, a novel metharcylamide monomer based on a pyrrolidinium group, inspired by the product of cyclisation of the diallylamine monomer was synthesised. This was achieved by reacting methacrylic anhydride with (R)-3-amino-1-N-Boc-pyrrolidine and used to generate polymers via Free Radical Polymerization, again with molecular weight variants. Comprehensive analysis of their antimicrobial activity and biocompatibility was undertaken. The higher molecular weight polymer showed toxic effects on mammalian cells, whilst polymers with lower molecular weights demonstrated bactericidal activity against both Gram-negative and Gram-positive bacteria, with a notably enhanced effect on Gram-positive bacteria. Finally, the antimicrobial activity of a Trӧger's Base polymer and the quaternized derivatives were investigated as potential antimicrobial surface coatings. Polymers were synthesized, coated onto surfaces via spin coating and evaluated for antimicrobial activity and biocompatibility.