Journal of Computer-Aided Molecular Design

, Volume 16, Issue 8, pp 611–633

QSAR of benzene derivatives: comparison of classical descriptors, quantum theoretic parameters and flip regression, exemplified by phenylalkylamine hallucinogens

Article

DOI: 10.1023/A:1021966231380

Cite this article as:
Clare, B.W. J Comput Aided Mol Des (2002) 16: 611. doi:10.1023/A:1021966231380

Abstract

A physical model of electronic effects in the QSAR of benzene derivatives, together with a regression technique for finding predictive equations, is presented. The model is simple, based on the quantum theoretic description of the benzene molecule, and accounts for the variance in activity of hallucinogenic phenylalkylamines as well as a classical description in terms of electronic (atomic charge, orbital energy), hydrophobic (Hansch π) and steric (substituent volume) terms. The new model involves the energies of four π-like near frontier orbitals and the orientations of their nodes. It is less affected by colinearity than the classical approach. This model more than any other illustrates the essential wave mechanical nature of the interaction of a drug with its receptor, as the π-like orbitals involved are standing waves of probability of finding an electron in a given location in the field of the atomic nuclei, and have no classical counterpart.

benzeneFOPAhallucinogenphenylalkylamineQSARquantumregressionsymmetry

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  1. 1.Department of ChemistryThe University of Western AustraliaCrawleyAustralia