Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers
Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are widely abused due to their psychostimulant effects. As they are chiral molecules, studies of their stereochemical stability (racemization can occur in certain temperatures and acidic/basic environments) and of their biological...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/5/2121 |
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| author | Ana Sofia Almeida Bárbara Silva João Pedro Silva José Augusto Pereira Fernando Remião Carla Fernandes |
| author_facet | Ana Sofia Almeida Bárbara Silva João Pedro Silva José Augusto Pereira Fernando Remião Carla Fernandes |
| author_sort | Ana Sofia Almeida |
| collection | DOAJ |
| description | Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are widely abused due to their psychostimulant effects. As they are chiral molecules, studies of their stereochemical stability (racemization can occur in certain temperatures and acidic/basic environments) and of their biological and/or toxicity effects (enantiomers might display different properties) are of great relevance. In this study, the liquid chromatography (LC) semi-preparative enantioresolution of MDPV was optimized to collect both enantiomers with high recovery rates and enantiomeric ratio (e.r.) values. The absolute configuration of the MDPV enantiomers was determined by electronic circular dichroism (ECD) with the aid of theoretical calculations. The first eluted enantiomer was identified as <i>S</i>-(-)-MDPV and the second eluted enantiomer was identified as <i>R</i>-(+)-MDPV. A racemization study was performed by LC-UV, showing enantiomers’ stability up to 48 h at room temperature and 24 h at 37 °C. Racemization was only affected by higher temperatures. The potential enantioselectivity of MDPV in cytotoxicity and in the expression of neuroplasticity-involved proteins—brain-derived neurotrophic factor (BDNF) and cyclin-dependent kinase 5 (Cdk5)—was also evaluated using SH-SY5Y neuroblastoma cells. No enantioselectivity was observed. |
| first_indexed | 2024-03-11T07:17:26Z |
| format | Article |
| id | doaj.art-3081ca637efa43a9a46343f714f47e06 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T07:17:26Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3081ca637efa43a9a46343f714f47e062023-11-17T08:12:16ZengMDPI AGMolecules1420-30492023-02-01285212110.3390/molecules28052121Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV EnantiomersAna Sofia Almeida0Bárbara Silva1João Pedro Silva2José Augusto Pereira3Fernando Remião4Carla Fernandes5Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira n° 228, 4050-313 Porto, PortugalUCIBIO—Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira n° 228, 4050-313 Porto, PortugalUCIBIO—Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira n° 228, 4050-313 Porto, PortugalCentro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, s/n, 4450-208 Matosinhos, PortugalUCIBIO—Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira n° 228, 4050-313 Porto, PortugalLaboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira n° 228, 4050-313 Porto, PortugalSynthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are widely abused due to their psychostimulant effects. As they are chiral molecules, studies of their stereochemical stability (racemization can occur in certain temperatures and acidic/basic environments) and of their biological and/or toxicity effects (enantiomers might display different properties) are of great relevance. In this study, the liquid chromatography (LC) semi-preparative enantioresolution of MDPV was optimized to collect both enantiomers with high recovery rates and enantiomeric ratio (e.r.) values. The absolute configuration of the MDPV enantiomers was determined by electronic circular dichroism (ECD) with the aid of theoretical calculations. The first eluted enantiomer was identified as <i>S</i>-(-)-MDPV and the second eluted enantiomer was identified as <i>R</i>-(+)-MDPV. A racemization study was performed by LC-UV, showing enantiomers’ stability up to 48 h at room temperature and 24 h at 37 °C. Racemization was only affected by higher temperatures. The potential enantioselectivity of MDPV in cytotoxicity and in the expression of neuroplasticity-involved proteins—brain-derived neurotrophic factor (BDNF) and cyclin-dependent kinase 5 (Cdk5)—was also evaluated using SH-SY5Y neuroblastoma cells. No enantioselectivity was observed.https://www.mdpi.com/1420-3049/28/5/2121absolute configurationelectronic circular dichroismenantioresolutionenantioselectivityliquid chromatographyMDPV |
| spellingShingle | Ana Sofia Almeida Bárbara Silva João Pedro Silva José Augusto Pereira Fernando Remião Carla Fernandes Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers Molecules absolute configuration electronic circular dichroism enantioresolution enantioselectivity liquid chromatography MDPV |
| title | Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers |
| title_full | Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers |
| title_fullStr | Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers |
| title_full_unstemmed | Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers |
| title_short | Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers |
| title_sort | semi preparative separation absolute configuration stereochemical stability and effects on human neuronal cells of mdpv enantiomers |
| topic | absolute configuration electronic circular dichroism enantioresolution enantioselectivity liquid chromatography MDPV |
| url | https://www.mdpi.com/1420-3049/28/5/2121 |
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