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Molecular structure, conformational analysis and charge distribution of pralidoxime: Ab initio and DFT studies
Author(s) -
Castro Alexandre T.,
FigueroaVillar Jose D.
Publication year - 2002
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.10302
Subject(s) - protonation , chemistry , oxime , density functional theory , computational chemistry , pralidoxime , ab initio , charge density , pyridinium , ion , quantum mechanics , medicinal chemistry , organic chemistry , physics , acetylcholinesterase , enzyme
A detailed structural study of pralidoxime (2‐PAM), the main antidote against organophosphate intoxication, was performed using Hartree‐Fock, Möller–Plesset (MP2), and density functional theory (Becke, Lee, Yang, and Paar [B3LYP]) methods. Rotational barriers, equilibrium geometries, and charge distributions were calculated, showing important differences between the two forms available in physiological conditions, namely with the oxime group protonated or unprotonated. For the protonated form, conjugation between the side chain and the pyridinium ring, although present, has little importance, resulting in a flexible structure. On the other hand, the unprotonated form has a more rigid structure and a smaller charge density on the oxime oxygen. Contrary to the common belief, those results strongly suggest that it may be the protonated form of 2‐PAM, instead of the unprotonated form, that is responsible for the antidote activity of this compound. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002