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

Donna M. Gasparro, David R P Almeida, F. Fülöp

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalJournal of Molecular Structure: THEOCHEM
Volume725
Issue number1-3
DOIs
Publication statusPublished - Jul 11 2005

Fingerprint

Selegiline
metabolites
dimensional analysis
Metabolites
Protons
Torsional stress
torsion
protons
Benzene
benzene
Orbital calculations
Carbon
Gas fuel analysis
carbon
Molecular orbitals
Conformations
Amines
molecular orbitals
amines
interactions

Keywords

  • Conformational analysis
  • Neuroprotection
  • R-(-)-desmethyldeprenyl

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computational Theory and Mathematics
  • Atomic and Molecular Physics, and Optics

Cite this

Ab initio multi-dimensional conformational analysis of R-(-)- desmethyldeprenyl : A potent neuroprotective metabolite of R-(-)-deprenyl. / Gasparro, Donna M.; Almeida, David R P; Fülöp, F.

In: Journal of Molecular Structure: THEOCHEM, Vol. 725, No. 1-3, 11.07.2005, p. 75-83.

Research output: Contribution to journalArticle

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