Enantioseparation and a comprehensive spectroscopic analysis of novel synthetic cathinones laterally substituted with a trifluoromethyl group

K Dobšíková; Ž Javorská; M Paškan; D Spálovská; P Trembulaková; J Herciková; M Kuchař; V Kozmík; M Kohout; V Setnička

doi:10.1016/j.saa.2023.122320

Enantioseparation and a comprehensive spectroscopic analysis of novel synthetic cathinones laterally substituted with a trifluoromethyl group

Spectrochim Acta A Mol Biomol Spectrosc. 2023 Apr 15:291:122320. doi: 10.1016/j.saa.2023.122320. Epub 2023 Jan 5.

Authors

Affiliations

¹ Department of Analytical Chemistry, University of Chemistry and Technology, Technická 5, Prague 6 166 28, Czech Republic.
² Department of Organic Chemistry, University of Chemistry and Technology, Technická 5, Prague 6 166 28, Czech Republic.
³ Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, Prague 6 166 28, Czech Republic; Psychedelic Research Centre, National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic.
⁴ Department of Analytical Chemistry, University of Chemistry and Technology, Technická 5, Prague 6 166 28, Czech Republic. Electronic address: vladimir.setnicka@vscht.cz.

PMID: 36634495
DOI: 10.1016/j.saa.2023.122320

Abstract

Recently, the number of structural modifications of synthetic cathinones has been growing making them the second largest group of new psychoactive substances in Europe. Although they are abused because of their various psychoactive effects, some compounds from this group also serve as pharmaceuticals. Since synthetic cathinones are chiral molecules with one chiral center, their biological, toxicological, and pharmacological properties may significantly differ according to their absolute configuration and enantiomeric excess. In this study, we have synthesized two substances bearing a pharmacologically interesting trifluoromethyl group and developed a chiral liquid chromatography method using a polysaccharide chiral stationary phase to separate the corresponding enantiomers of both these drugs. Subsequently, we utilized molecular spectroscopic methods including chiroptical (electronic circular dichroism and vibrational circular dichroism) and non-polarizable (infrared and ultraviolet absorption) spectroscopies. In combination with density functional theory calculations, we have obtained stable conformers of selected enantiomers in solution and their relative abundances, which we used to simulate their spectra. The experimental and calculated data have been used to elucidate the 3D structure of the enantiomerically pure compounds and assign the absolute configuration of all prepared compounds.

Keywords: Chiral separation; Chiroptical spectroscopy; DFT calculations; Methcathinone; Synthetic cathinones.