The relationship of charge transfer complexes to frontier orbital energies in QSAR

Abstract

Frontier orbital energies, calculated by fast and approximate semiempirical methods, are widely used as molecular descriptors in medicinal chemistry. The traditional justification is that they represent measures of the ability of drug molecules to participate in the formation of charge transfer complexes. For both theoretical reasons and as a consequence of the drastic approximations inherent in the semiempirical methods, some doubt exists about the basis of this assumption. A computational study has been made of the stability of charge transfer complexes of benzene and methylated benzenes with four electron acceptors by the semiempirical PM3 method. The results support the traditional view that the energy of the highest occupied molecular orbital of the donor molecule is an indicator of the ability of the donor to form charge transfer complexes with electron acceptors. It was found that the heat of formation of the complex could be calculated, which correlated well with the measured stability constant of the complex, taken from the literature, and with measures of transfer of charge in both the ground state and excited state. The energy of the lowest unoccupied molecular orbital of the complex, calculated by PM3, was an extremely good measure of the ability of the donor-acceptor pair to form such a complex.