A theoretical conformational study of R-(−)-Deprenyl, a selective MAO-B inhibitor with potential anti-aging effects: an ab initio multi-dimensional conformational analysis

R-(−)-Deprenyl is a drug with proven efficacy currently used in the treatment of Parkinson's Disease (PD) and which has been shown to increase lifespan in rats when administered in the appropriate dosages. As such, multi-dimensional conformational analysis (MDCA) using molecular orbital (MO) calculations at Restricted Hartree-Fock, RHF/3-21G, was performed as a method of scanning the surface of N-protonated R-(−)-Deprenyl to divulge its conformational characteristics. The MDCA of N-protonated R-(−)-Deprenyl revealed a total of 29 converged minima of a possible 54 with a defined subset of three low energy structures. The results indicate that the dominant conformational effect in R-(−)-Deprenyl is the Gauche Effect seen between the sp2 carbon on the benzene and the sp3 tetrahedral carbon on its side chain. Furthermore, two intramolecular attractive forces confer stability to converged conformers of the N-protonated R-(−)-Deprenyl surface; electrostatic interactions between the amine proton and the aromatic benzene ring (N-H⋯Ar) and electrostatic interactions between the amine proton and the carbon-carbon triple bond (N-H⋯CC). Sterics between the methyl group attached to the positive nitrogen center and the aromatic benzene also effect the viable conformations and energetics of the surface of N-protonated R-(−)-Deprenyl.