Methylone and pentylone: structural analysis of new psychoactive substances

Abstract

Purpose The growing availability of new psychoactive substances with unknown toxicity is alarming all over the world. The simplicity of acquiring these drugs of abuse from internet markets has caused an increase in the total number of seizures. We present the first systematic spectroscopic study of methylone and pentylone, which are in the class of synthetic cathinones. Methods High performance liquid chromatography (HPLC) was used for the enantioseparation of methylone and pentylone. The substances were further analysed by the conventional methods of ultraviolet (UV) and infrared (IR) absorption and chiroptical methods, specifically electronic circular dichroism (ECD) and vibrational circular dichroism (VCD). The obtained data were supported with the density functional theory (DFT) calculations using the B3LYP or B3PW91 functional and 6-311++G(d,p) basis sets, including the solvent effects. Results The 3D structure of methylone and pentylone in solution was revealed. Moreover, the chiral separation of both studied substances was achieved and the absolute configuration of the respective enantiomers was determined. Conclusion Vibrational circular dichroism spectroscopy seems to be the best of the methods employed to distinguish structurally similar chiral substances, especially in combination with quantum chemical calculations. According to the structural analysis, 5 and 9 stable conformers of methylone and pentylone, respectively, were revealed in an aqueous solution. Finally, very good agreement between the experimental and simulated spectra was achieved.

Synthesis and absolute configuration of cyclic synthetic cathinones derived from α‐tetralone

“…After ascertaining the absolute configuration of the studied cyclic synthetic cathinones, we realized that the chromatographic elution order of enantiomers differs from that observed for previously studied compounds. For all synthetic cathinones previously synthesized and studied by us, [43][44][45][46] the absolute configuration of the first and second eluting enantiomers was (S)-and (R)-, respectively. In the previous studies as well as here, the chiral stationary phase utilized for the preparative chiral resolution of the enantiomers was identical (Chiralpak IA).…”

Interpol Review of Drug Analysis 2019-2022

“…2019 all regioisomers of CDC (i.e., 2-CDC, 3-CDC and 4-CDC) and CEC (i.e., 2-CEC, 3-CEC and 4-CEC) were acquired and analyzed using gas chromatography-electron ionization-mass spectrometry (GC-EI-MS), LC-DAD, FTIR and GC–CI–MS [ 534 ]review of the forensic and clinical aspects of bupropion (structurally related to cathinones) [ 535 ]; rapid tentative identification of synthetic cathinones in seized products using LC-MS/MS [ 536 ]; review [ 537 ]; chiral capillary electrophoresis method for the enantioseparation of 61 cathinone and pyrovalerone derivatives [ 538 ]; Four compounds (cathinone derivatives N-ethyl-2-amino-1-phenylhexan-1-one hydrochloride, N-methyl-2-amino-1-(4-methylphenyl)-3-methoxypropan-1-one hydrochloride, N-ethyl-2-amino-1-(3,4-methylenedioxyphenyl)pentan-1-one hydrochloride and N-butyl-2-amino-1-(4-chlorophenyl)propan-1-one hydrochloride) found during seizure by drug enforcement agencies were identified and characterized by NMR, IR and Raman spectroscopies and X-ray crystallography [ 539 ]; differentiation of o-, m-, and p-fluoro-alpha-pyrrolidinopropiophenones by benzyltrimethylammonium hydroxide (Triton B)-mediated one-pot reaction [ 540 ]; review [ 541 ]; spectroscopic characterization of four synthetic Cathinones: 1-(4-Chlorophenyl)-2-(Dimethylamino)Propan-1-One (N-Methyl-Clephedrone, 4-CDC), 1-(1,3-Benzodioxol-5-yl)-2-(Tert-Butylamino)Propan-1-One (tBuONE, Tertylone, MDPT), 1-(4-Fluorophenyl)-2-(Pyrrolidin-1-yl)Hexan-1-One (4F-PHP) and 2-(Ethylamino)-1-(3-Methylphenyl)Propan-1-One (3-Methyl-Ethylcathinone, 3-MEC) using single-crystal X-ray analysis, NMR, UHPLC-QQQ-MS/MS and GC-MS [ 542 ]; probe for quantitation and screening of 4-chloromethcathinone and cathinone analogues at crime scenes [ 543 ]; 2020 UV absorption properties of synthetic cathinones [ 544 ]; Study combines isotope-labeling, multi-stage mass spectrometry (MSn) and accurate mass measurements with high-resolution mass spectrometry (HRMS) to enhance the current understanding of the fragmentation pathways of alpha-pyrrolidinophenone synthetic cathinones and their application to the identification of emerging synthetic cathinone derivatives [ 545 ]; quantitative determination of chiral cathinone in fresh samples of Catha edulis [ 546 ]; review [ 547 ]; NMR methodology for chiral discrimination for several cathinones [ 548 ]; DFT calculations for prediction of Raman and infra-red spectra and activities of newly synthesized cathinones [ 549 ]; review [ 550 ]; structural analysis of new psychoactive substances methylone and pentylone [ 551 ]; the determination and separation of R- and S-enantiomers of methylone and ethylone by LC-MS/MS analysis [ 552 ]; analysis of synthetic cathinones in seized drugs using a portable low microflow LC with dual capillary columns and dual wavelength UV detection [ 553 ]; 2021 micellar electrokinetic chromatography (MEKC) mode of CE hyphenated to laser-induced fluorescence (LI...…”

Conformational analysis of amphetamine and methamphetamine: a comprehensive approach by vibrational and chiroptical spectroscopy

“…It is of particular importance to analyse and study the drugs of abuse in the same form as they are taken into the organism. [15][16][17][18][19] Based on that, this work examines amphetamine and methamphetamine hydrochloride diluted in an aqueous solution.…”