Synthesis, crystal structure, and biological activity of menthol-based chiral quaternary phosphonium salts (CQPSs)

Eight new chiral quaternary phosphonium salts (CQPSs) comprising (1R,2S,5R)-(‒)-menthyl or (1S,2R,5S)-( +)-menthyl group have been synthesized. The relationships between the physical chemical properties of CQPSs and the steric hindrance of the cation, the nature of the anion, and chiral center in the substituent are discussed. According to X-ray diffraction data, pairs of isomers with n-butyl substituents may crystallize in two different crystal systems, which is presumably determined by the conformational flexibility of alkyl chains. In the case of the second pair of isomers bearing tert-butyl fragments, this phenomenon is not observed. The study of the antimicrobial properties of CQPSs against Gram-positive bacteria Staphylococcus aureus, including Methicillin-resistant strains MRSA-1 and MRSA-2, Bacillus cereus and Enterococcus faecalis; the Gram-negative pathogenic bacteria: Escherichia coli and Pseudomonas aeruginosa; and the fungus Candida albicans has demonstrated the differences in antibacterial activity of chiral isomers as well as compounds with different steric hindrance of the phosphonium cation. The mechanism of action of CQPSs on the bacterial cells was evaluated using the crystal violet assay and the LIVE/DEAD BacLightTM Bacterial Viability Method.