Dynamic Constitutional Frameworks as antibacterial and antibiofilm agents.

Abstract

Dynamic Constitutional Frameworks (DCFs) were synthesized and screened for biofilm inhibition or disruption. They are composed of a trialdehyde core reversibly linked to a diamine PEG connector and to a variety of neutral, anionic or cationic heads, to generate a library of DCFs to generate multivalent dendritic architectures in the presence of Pseudomonas aeruginosa and Staphylococcus aureus. The best DCFs were always polycationic and the nature of the cationic heads significantly impact the antibiofilm activity. The best antibiofilm activity was observed for DCF3B, displaying a polyethyleneimine head. Interestingly, a simple inactive guanidinium functional head, strongly inhibited biofilm growth when assayed as a multivalent DCF3C. Using a more advanced in vitro biofilm model of chronic wound infection, DCF3C was found significantly superior than all other DCFs. These results demonstrate 1) the versatility and effectiveness of DCFs as low cost and efficient systems for antibiofilm disruption 2) the efficiency of dynamic chemistry as a discovery technology.