Highly Effective and Broad-Spectrum Antimicrobial Quaternary Ammonium Salts Containing Camphene Structure: Preparation, Surface-Active Properties, and Bioassay

Abstract

A series of novel quaternary ammonium salts (QASs) (4a–4n) comprising a camphene moiety were synthesized for the first time. Fourteen examples were prepared from camphene through Prins reaction, halogenation, and quaternarization, successively. The structures of the synthesized QASs were analyzed by Fourier transform infrared spectroscopy, 1H NMR, 13C NMR and high-resolution mass spectrometry. Surface-active properties, emulsifying abilities, and foaming properties of the investigated compounds were then studied. The antimicrobial activities of these QASs against Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae), and fungi species (Candida albicans, Candida tropicalis, and Aspergillus niger) were determined by the microdilution method. The results showed that the chemical structural factors, including types of substitutes and alkyl chain length, might be correlated with the lipid–water partition coefficient (cLog P), which played a critical role in the antimicrobial process. Compounds with alkyl chain lengths (N) in the range of 10–14 were relatively more active, while compounds bearing pyridinium, benzyl, methylimidazolium groups, or varied alkyl chain lengths (N < 5 and N > 16) were almost inactive. Compound 4k possessing a dodecyl group exhibited the most effective and broad-spectrum antimicrobial activity against almost all tested bacteria and fungi with the minimal inhibitory concentration values ranging from 0.24 to 0.98 μg/mL.