Bushy‐Tailed QACs: The Development of Multicationic Quaternary Ammonium Compounds with a High Degree of Alkyl Chain Substitution

Abstract

Quaternary ammonium compounds have served as a first line of protection for human health as surface disinfectants and sanitizers for nearly a century. However, increasing levels of bacterial resistance have spurred the development of novel QAC architectures. In light of the observed reduction in eukaryotic cell toxicity when the alkyl chains on QACs are shorter in nature (≤10C), we prepared 47 QAC architectures that bear multiple short alkyl chains appended to up to three cationic groups, thus rendering them “bushy‐tailed” multiQACs. Antibacterial activity was strong (often ~1‐4 μM) in a varied set of bushy‐tailed architectures, though observed therapeutic indices were not significantly improved over QAC structures bearing fewer and longer alkyl chains.