Molecular Descriptors and the Electronic Structure
Bögel Horst · 2012
The investigation of structure–property relationships is one of the most challenging tasks in molecular sciences to create a more systematic picture of chemical compounds and their properties and biological activities. Quantitative structure–activity (QSAR) relationship, molecular modeling, and quantum chemistry provide powerful computational methods to handle many objects and features to elucidate mathematical models. There are thousands of possible descriptors, but quantum chemical molecular orbitals and the electronic structure are key features to create mathematical models which are useful for mechanistic interpretations and to accumulate pieces of knowledge. It is shown that very convenient features, such as electron densities (respectively atomic charges or molecular electrostatic potentials), are local representatives of the total energy of the molecule. In combination with localized molecular orbitals (LMO), they characterize charge and orbital controlled interactions in the sense of the perturbation theoretical approach by Klopman. The proton affinity of nitrogen-heterocyclic compounds could be predicted by the AM1-calculated LMOs of the lone-pair electrons. An investigation of the stability of the five structural isomers of hexane has shown that some of topological descriptors are quite similar useful in QSAR models. Some of the investigated physicochemical properties show great similarities in their models, which could be helpful to extend our picture of the structure–property relationships. All properties of a molecule are based on the same electronic structure and its dynamics.