High-Throughput Synthesis of Antimicrobial Copolymers and Rapid Evaluation of Their Bioactivity

Abstract

The growing trend in antimicrobial resistance is a potential threat to our society. Due to this, the development of new antimicrobial compounds is urgently required. High-throughput compositional analysis, combined with recent advances in polymerization protocols, allows for rapid production of potentially antimicrobial compounds with minimal expertise. This can provide the impetus for correlating activity with composition and functionality. In this study, we have used high-throughput photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization to test the combinations of seven different monomers using 120 different formulations against three distinct bacterial species: Gram-negative Pseudomonas aeruginosa, Gram-positive Staphylococcus aureus, and Mycobacterium smegmatis. Through variations in composition, we have demonstrated the potential of high-throughput PET-RAFT for highly reproducible products, as well as simultaneous testing of multiple variables. Results indicate that primary amines work best against Gram-negative P. aeruginosa, while quaternary ammonium provides activity versus M. smegmatis. Copolymers of these provide avenues for further optimization, especially in the case of quaternary ammonium functionalities.

Amphiphilic water soluble cationic ring opening metathesis copolymer as an antibacterial agent

“…Suer et al also observed same phenomenon for polar phosponiumbased ROMP polymer . GPC calibration with linear, non‐ionic pullulan standards resulted in different hydrodynamic volumes with respect to the cationic‐based copolymers, which can lead to a strong deviation . However, GPC determines weight average molecular weight and number average molecular weight ratio and it indicated the broad distribution for the obtained copolymers (Table ) and featuring Ð of polymers were 1.34–4.78 (see the GPC spectra at Figure S61).…”

Progress and Perspectives Beyond Traditional RAFT Polymerization

“…[152][153][154][155] In recent years, the ability to conduct RAFT without traditional deoxygenation protocols has facilitated a growing number of benchtop combinatorial and high-throughput studies, which are particularly advantageous for generating polymers with specific biological interactions. Enzymatic degassing [84,156] and photochemical oxygen sequestration [155,[157][158][159][160][161][162][163][164][165][166] have afforded access to (ultra)low reaction volumes and finely controlled reagent conditions that are common prerequisites for high-throughput translation.…”

New Light in Polymer Science: Photoinduced Reversible Addition-Fragmentation Chain Transfer Polymerization (PET-RAFT) as Innovative Strategy for the Synthesis of Advanced Materials

“…High throughput technology afforded the synthesis of glycopolymers composed of hydrophobic, cationic, and sugar repeating units with variable compositions; their antibacterial activity and cytotoxicity were easily tested. Gibson group [ 120 ], as well as Boyer and coworkers [ 121 , 122 ], demonstrated the rapid PET-RAFT synthesis of a library of antimicrobial polymers, using visible light irradiation, without the need for degassing or purification step. Boyer investigated the effect of monomer distribution within linear high-order quasi-block copolymers on their antimicrobial properties.…”