Extension of the frontier reactivity indices to groups of atoms and application to quantitative structure-activity relationship studies

The concept of frontier reactivity index, proposed by Fukui et al. (J. Chem. Phys., 20 (1952) 722), was extended to groups of atoms. The purpose of this procedure is to simulate frontier indices capable of predicting the susceptibility of a chemical group to an external electronic interaction, such as nucleophilic, electrophilic or radical. The group frontier indices can be useful in quantitative structure-activity relationship (QSAR) studies, where substituent constants for groups of atoms are widely used. The group frontier indices are obtained through the sum of the corresponding atomic frontier indices. The atomic frontier indices were computed from AM1 wavefunction coefficients. The frontier indices considered in this article, i.e. frontier electron, orbital and radical densities, are shown to be relatively independent of the molecular geometry. We applied the group frontier index concept to a QSAR study of triazene derivatives. The group frontier indices that appear to be significant in the correlation analysis are consistent with the known hydroxylation mechanism of triazene induced mutagenesis.