Ab initio multi-dimensional conformational analysis of R-(−)-desmethyldeprenyl: A potent neuroprotective metabolite of R-(−)-deprenyl

R-(−)-desmethyldeprenyl, a primary metabolite of R-(−)-deprenyl, has been shown to have more potency in neuroprotection then its parent compound. Since some of R-(−)-deprenyl's efficacy has been attributed to R-(−)-desmethyldeprenyl, the stereochemical surface of N-protonated R-(−)-desmethyldeprenyl was scanned via Multi Dimentional Conformational Analysis (MDCA) using gas phase molecular orbital (MO) calculations at Restricted Hartree Fock RHF/3-21G using Gaussian 98 to identify highly occupied conformations and to divulge its conformational characteristics. Results indicated a dominant gauche effect at χ1, where the gauche orientation is always preferred over the syn/anti. Torsion χ2 dictates the presence of proton benzene interactions; when χ2 is equal to anti both amine protons of N-protonated R-(−)-desmethyldeprenyl are oriented such that they cannot form intramolecular attractive forces (IMAF) with the benzene ring. Furthermore, energetics indicates that H29-C6 IMAF is favoured over H29-C1, H26-C6 and H26-C1 IMAF's. Torsion χ4 of N-protonated R(−)-desmethylselegiline predicts proton carbon-carbon triple bond interactions.