Use of electron-electron repulsion energy as a molecular descriptor in QSAR and QSPR studies.

Abstract

Electron-electron repulsion energy (<Vee>) is presented as a new molecular descriptor to be employed in QSAR and QSPR studies. Here it is shown that this electronic energy parameter is connected to molecular quantum similarity measures (MQSM), and as a consequence can be considered as a complement to steric and electronic parameters in description of molecular properties and biological responses of organic compounds. The present strategy considers the molecule as a whole, thus there is no need to employ contributions of isolated fragments as in many calculations of molecular descriptors, like log P or the Free-Wilson analysis. The procedure has been tested in a widespread set of molecules: alcohols, alkanamides, indole derivatives and 1-alkylimidazoles. Molecular properties, as well as toxicity, are correlated using <Vee> as a parameter, and extensions to the method are given for handling difficult systems. In almost all studied cases, satisfactory linear relationships were finally obtained.