There is an urgent need to identify new, non-traditional antimicrobials. The discovery of new polymeric antimicrobials is often limited by current low-throughput synthetic tools, which means that limited chemical space has been explored and 'hot spots' for activity are based on screening of libraries containing just 10's of polymers, meaning that true optimisation and discovery is not possible.<br/>We are using photochemical “in-air” polymerization using trithiocarbonates as photo-RAFT or photo-iniferter agents. All polymerizations are conducted open to air without any degassing, and using liquid handling robots to manipulate the reagents. Crucially, the polymerizations can be conducted in 96 or 384 well plates, and are hence prepared in a format ready for rapid screening of antimicrobial function.<br/>In this talk I will first discuss the methodologies used and the results of an initial screen which enabled identification of antimicrobial copolymers with enhanced activity against E coli. Mechanistic studies showed that this polymer was bacteriostatic and did not seem to lyse the cell membranes, implying an alternative mode of action which is not entirely based on breaking the bacteiral cell membranes.<br/>Secondly, I will discuss how this method has been used to create extremely large libraries (100's) of polymers and how they are being used to screen for activity against Mycobacteria. Mycobacteria (which include Mycobacterium Tuberculosis) have a unique cell wall, rich in complex glycas not found in other bacterial species and are particularly hard to treat with traditional drugs due to this permeability barrier. The screening strategy has allowed identification of complex copolymers which show 20 - 100 fold enhancements in activity against various Mycobacteria including Mycobacterium tuberculosis

Photo-chemical discovery of anti(myco)bacterial polymers

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.