Conformational analysis, energy profile, and structural-electronic properties evaluation of mephedrone derivatives employing quantum-mechanical models

Mephedrone (4-methyl-meth-cathinone) or 4-MMC and its derivative 3-MMC are analogs of cathinone which act as non-selective substrates for monoamine transporters, facilitating a neurotransmitter release via the reversal of normal transporter fluxes. The pharmacological effects like paranoia, hallucinations, euphoria, aggressiveness, and psychosis make these molecules “abusive designer drugs.” In the present study, conformations of all isomers of 3- and 4-MMC have been studied at the quantum-chemical level. Calculations have been performed using Møller-Plesset second-order (MP2) methods with 6-31G(d, p) basis sets. Present study shows that there are low-energy conformers for the meta (3-MMC) and para (4-MMC) isomers that are connected by way of low-barrier transition states. Natural bond orbital (NBO) analyses have been also performed to corroborate the results as estimated from the MP2 calculations. The molecular electrostatic potential surface data for each molecule has been calculated, revealing likely that reaction sites and probable metabolism pathway for both derivatives have been proposed. IR spectra for MMC derivatives have been compared with experimental data, and rotational transition states connecting all conformers have been reported.