Quaternary ammonium compounds (QACs) are commonly used as disinfectants, employed both for their ease of preparation as well as their broad-spectrum antimicrobial activity. The simple structure of benzalkonium chloride, a single quaternary ammonium bearing an alkyl chain of varying length, provides the compound’s amphiphilicity, as well as an opportunity for improvement. We have observed that QACs bearing more than one cation (i.e., bisQACs) provide greater efficacy in killing bacteria. In this project, we synthesized 21 mono- and bisQACs from different bisamine starting materials, piperazine and DABCO, installing varied alkyl and amide-containing side chains to investigate the effects of structural rigidity on antiseptic activity. The compounds were tested against 6 bacterial strains and compared to MICs of the previously synthesized TMEDA-12,12, which is essentially a non-rigid bisQAC. Surprisingly, bisQAC amphiphiles bearing the rigid DABCO core showed increased antimicrobial activity. DABCO-12,12 in particular showed submicromolar activity against a MRSA strain, suggesting that a more rigid core structure leads to improved activity.

Insights into rigidity-activity relationships in bisQAC amphiphilic antiseptics

2019 Spring National Meeting

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