Synthesis of 1,4-di̇azabi̇cyclo[2.2.2]octane based cationic polymers with ring opening metathesis polymerization technique and examination of their antibacterial activity

Bacterial infection, as a global problem, become more important especially in the last decades due to rising death rates. The new generation antibiotics are quite important for fighting against the bacteria. Basically, there are two main categories of new generation antibiotics: the host defense peptides and their synthetic analogues of host defense peptides. Antimicrobial synthetic polymers are one of the most important mimics for host defense peptides. The stable behavior of these polymers at physiological environments and their easy and cheap synthesization make them superior comparing to other natural peptide derivatives. It is also well known that amphiphilic polymers disrupt the cell membranes of the bacteria and can realize the cell death. It is suggested that the bacteria will not be resistant against this destruction mechanism. This paper focuses on the synthesis of polymers with well defined architecture derived by Ring Opening Metathesis Polymerization technique. The synthesized polymers have a cationic structure with the advantage of having high interaction with the anionic surfaces of the bacteria. In the scope of this work, the monomers containing DABCO and pyridine have been used to synthesize homopolymers with molecular weights of 3000 g/mole and 10000 g/mole and their copolymers with molecular weights of 5000 g/mole. The effect of hydrophobicity and cationic charge denstiy on the antimicrobial activity was investigated. E.coli and S.aureus were used to determine antimicrobial activity of polymers on solid surface (glass) and solution phase. Cytotoxicity of the polymers were determined by hemolytic concentration (HC50). Florecein test was used to calculate cationic charge density on coating glass with polymers. Cationic charge density was used to investigate mechanism of antimicrobial efficiency on coating glass surface with polymer. Also zeta potential studies was applied to understand structure- acivity relationship. During the experiments, it has been observed that DABCO based homopolymer (D_10) has the highest activity (S.aureus= 8 µg/mL). All polymers show low antimicrobial activity against E.coli ( < 256 µg/mL). Hemolytic concantration values of polymers were found ~2000 µg/mL.