Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers

Abstract

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 S-(-)-MDPV and the second eluted enantiomer was identified as R-(+)-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.

Keywords

• absolute configuration
• electronic circular dichroism
• enantioresolution
• enantioselectivity
• liquid chromatography
• MDPV