Soft QPCs: Biscationic Quaternary Phosphonium Compounds as Soft Antimicrobial Agents

Abstract

Quaternary ammonium compounds (QACs) serve as a first line of defense against infectious pathogens. As resistance to QACs emerges in the environment, the development of next-generation disinfectants is of utmost priority for human health. Balancing antibacterial potency with environmental considerations is required to effectively counter the development of bacterial resistance. To address this challenge, a series of 14 novel biscationic quaternary phosphonium compounds (bisQPCs) have been prepared as amphiphilic disinfectants through straightforward, high-yielding alkylation reactions. These compounds feature decomposable or “soft” amide moieties in their side chains, anticipated to promote decomposition under environmental conditions. Strong bioactivity against a panel of seven bacterial pathogens was observed, highlighted by single-digit micromolar activity for compounds P6P-12A,12A and P3P-12A,12A. Hydrolysis experiments in pure water and in buffers of varying pH revealed surprising decomposition of the soft QPCs under basic conditions at the phosphonium center, leading to inactive phosphine oxide products; QPC stability (>24 h) was maintained in neutral solutions. The results of this work unveil soft QPCs as a potent and environmentally conscious new class of bisQPC disinfectants.

Multiheaded Cationic Surfactants with Dedicated Functionalities: Design, Synthetic Strategies, Self-Assembly and Performance

“…Therefore, the Halder research team's efforts to produce dicephalic cationic surfactants with an easily cleavable ester bond in their structure may eventually result in more effective disinfectants and antiseptics for food and body surfaces than conventional single-headed cationic surfactants. Star-shaped surfactants with multiheaded groups are part of another significant subgroup of MHCSs [152][153][154][155]. The multi-cationic homologs of benzalkonium chloride (BAC) are one of the structures that research teams are now working on, and they look the most promising.…”

Further Study of the Polar Group’s Influence on the Antibacterial Activity of the 3-Substituted Quinuclidine Salts with Long Alkyl Chains

“…Indeed, their extensive work on multiQACs has yielded structures with superior and broad activity [ 15 , 16 , 17 ]. To overcome bacterial resistance, the same research group has also proposed replacing the positive quaternary nitrogen with other atoms such as phosphonium or sulfur in mono- and multiQAC versions [ 18 , 19 , 20 , 21 ].…”