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Quantum chemistry in QSAR : Anticonvulsivant activity of VPA derivatives
Author(s) -
BrunoBlanch Luis,
Estiuz Guillermina L.
Publication year - 1995
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.560560705
Subject(s) - chemistry , computational chemistry , conformational isomerism , electronic structure , quantum chemistry , molecule , carbon atom , organic chemistry , alkyl , supramolecular chemistry
A QSAR analysis of a series of Valproic Acid (vpa) derivatives is given, which shows the importance of hydrophobic and electronic effects as determinants of the anticonvulsivant activity. The statistical analysis allows one to infer that the electron acceptor capability of the carboxylic carbon atom may guide electrostatic interactions of the molecules with the receptor site, in those cases where the lipophilic requirements are satisfied. Both the anticonvulsivant activity and the calculated lipophilic parameters (log P values) are taken from the literature, whereas the electronic descriptors result from Intermediate Neglect of Differential Overlap calculations at the Configuration Interaction level, ( INDO/S‐CI parametrization), for the most stable conformers of each derivative. The protein environment is modeled as a dielectric continuum in a Self‐Consistent Reaction Field approach. The conformational analysis is based on AMI calculations. © 1995 John Wiley & Sons, Inc.