Accession Number : AD0807775

Title :   A QUANTUM MECHANICAL EVALUATION OF THE MECHANISM OF ACTION OF 2-PAM CHLORIDE AND ANALOGS.

Descriptive Note : Final rept. 27 Apr-27 Nov 66,

Corporate Author : MARTIN MARIETTA CORP BALTIMORE MD RESEARCH INST FOR ADVANCED STUDIES

Personal Author(s) : Kaufman, Joyce J. ; Hamann, Jon R.

Report Date : FEB 1967

Pagination or Media Count : 100

Abstract : The overall objective of this research was to establish the relationship between the pharmacological action of 2-PAM chloride analogs and their electronic structure. To realize this goal extensive 'extended Huckel' (XHMO) LCAO-MO quantum chemical calculations, using both the Cusachs' and the Mulliken-Wolfsberg-Helmholz models, were performed on 2-PAM, deprotonated 2-PAM (2-PA), 3-PAM and 4-PAM. Two major topics to which particular attention was devoted were the conformational isomerism and the molecular electronic distributions. The calculations led to exciting results for both of these topics. The calculated energies of the conformational isomers indicated that non-planar forms would have a stability of the same magnitude as the crystallographically determined planar form. This implies that these out of plane conformers might play an important role in the reaction of 2-PAM. The calculated electronic charge distributions show the pyridinium nitrogen to be negatively charged (even though it was inputted with a formal positive charge). This difference in charge distribution from the conventional picture of pyridinium compounds forces one to reexamine the ordinarily postulated mechanism of reaction of 2-PAM. Calculations were also performed on deprotonated 2-PAM (2-PA) and on 3-PAM and 4-PAM. (Author)

Descriptors :   *OXIMES), (*PYRIDINES, (*QUANTUM THEORY, REACTION KINETICS), (*REACTION KINETICS, THERAPY), ATOMIC ORBITALS, MOLECULAR ORBITALS, MOLECULAR ROTATION, ELECTRONS, INTERACTIONS, WAVE FUNCTIONS, THEORY, PHARMACOLOGY, ORGANIC PHOSPHORUS COMPOUNDS, MATHEMATICAL ANALYSIS, ITERATIONS, STABILITY, PROTONS, REMOVAL, APPROXIMATION(MATHEMATICS), NUCLEAR SHELL MODELS, MATRICES(MATHEMATICS), CHEMICAL BONDS, ENERGY, DISTRIBUTION.

Subject Categories : Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE