
Accession Number : AD0807775
Title : A QUANTUM MECHANICAL EVALUATION OF THE MECHANISM OF ACTION OF 2PAM CHLORIDE AND ANALOGS.
Descriptive Note : Final rept. 27 Apr27 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 2PAM chloride analogs and their electronic structure. To realize this goal extensive 'extended Huckel' (XHMO) LCAOMO quantum chemical calculations, using both the Cusachs' and the MullikenWolfsbergHelmholz models, were performed on 2PAM, deprotonated 2PAM (2PA), 3PAM and 4PAM. 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 nonplanar 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 2PAM. 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 2PAM. Calculations were also performed on deprotonated 2PAM (2PA) and on 3PAM and 4PAM. (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