Frontier orbital energies in quantitative structure-activity relationships: A comparison of quantum chemical methods

Abstract

The energies of the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO) have long been used as descriptors in QSAR (Quantitative Structure-Activity Relationships). It is shown that different quantum chemical methods of calculating these energies yield results which sometimes correlate poorly with each other. This could seriously affect physical interpretation of QSAR equations. A comparison is made between HOMO and LUMO energies and their differences and sums (hardness and electronegativity) calculated by some of the best knownab initio and semi-empirical methods for two series of simple organic molecules. The difference between the HOMO and LUMO energies correlates better between methods than does either alone, and their sum correlates relatively poorly. MINDO/3 (Modified Intermediate Neglect of Differential Overlap, version 3) is the poorest method in terms of correlation with the more extended basis setab initio methods, followed by CNDO (Complete Neglect of Differential Overlap) and INDO (Intermediate Neglect of Differential Overlap). The best semi-empirical methods, in terms of correlation with experiment and the more extended basis setab initio calculations, are MNDO (Modified Neglect of Differential Overlap), AM1 (Austin Model 1) and PM3 (Parametric Method 3). The simplestab initio method, STO-3G, does not agree as well with the extended basis set calculations or with experimental results as the more advanced semi-empirical methods.