Structural Analysis of MDMA in Solution by Methods of Chiroptical Spectroscopy Supported by DFT Calculations

Abstract The synthetic drug 3,4-methylenedioxy-N-methyl-amphetamine (MDMA), also known as ecstasy, is one of the most abused dance drugs spread around the world. The number of seizures of ecstasy tablets increases every year. As MDMA is a chiral substance with one chiral center, it may occur as two enantiomers. These enantiomers have different physiological effects, therefore the reliable detection of individual enantiomers and a detailed structural description are highly desirable. In this work, the 3D structure of MDMA in solution was investigated by vibrational circular dichroism and electronic circular dichroism supplemented by conventional infrared and ultraviolet absorption spectroscopies. The obtained results were supported by density functional theory (DFT) calculations using different levels of theory. Initially, sixty-four starting geometries were optimized at the B3LYP/6-31+G(d) level including the solvent effects. Four stable conformers were further reoptimized at higher levels of theory and the spectra were also simulated. The experimental and the calculated spectra were compared via the similarity index. The spectra comparison showed very good agreement, which enabled us to describe the molecular structure of MDMA in detail.