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

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Abstract

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.

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Data availability

CCDC contains the supplementary crystallographic data for CQPS. These data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: 44) 1223–336–033 or email: deposit@ccdc.cam.ac.uk.

Code availability

Not applicable.

Abbreviations

CQPS:

Chiral quaternary phosphonium salt

IL:

Ionic liquid

CIL:

Chiral ionic liquid

HPLC:

High-performance liquid chromatography

DMSO:

Dimethyl sulfoxide

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Acknowledgements

The support and advice from Academician of Russian Academy of Sciences Valentin P. Ananikov are gratefully acknowledged.

Funding

This research was supported by the Russian Science Foundation (RSF grant no. 22–23-20161).

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Authors and Affiliations

  1. N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russian Federation

    Daria M. Arkhipova, Aida I. Samigullina & Mikhail E. Minyaev

  2. Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of Russian Academy of Sciences, Arbuzov Str. 8, Kazan, 420088, Russian Federation

    Anna P. Lyubina, Alexandra D. Voloshina & Vadim V. Ermolaev

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  1. Daria M. Arkhipova
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  2. Aida I. Samigullina
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  3. Mikhail E. Minyaev
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  4. Anna P. Lyubina
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  5. Alexandra D. Voloshina
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  6. Vadim V. Ermolaev
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Contributions

Daria M. Arkhipova, Aida I. Samigullina and Anna P. Lyubina carried out the experimental work and analyzed the data. Daria M. Arkhipova, Alexandra D. Voloshina, Mikhail E. Minyaev and Vadim V. Ermolaev, conceptualization, data curation and writing—original draft. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Vadim V. Ermolaev.

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Arkhipova, D.M., Samigullina, A.I., Minyaev, M.E. et al. Synthesis, crystal structure, and biological activity of menthol-based chiral quaternary phosphonium salts (CQPSs). Struct Chem 35, 75–88 (2024). https://doi.org/10.1007/s11224-023-02259-0

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