Frontier molecular orbital interactions between intercalating quinoline alkaloids and DNA base pairs: An ab initio investigation

The objective of this research is to test the hypothesis that the lowest energy orientation of a DNA intercalator may be predicted by inspection of frontier molecular orbital (FMO) overlap. Molecular orbital calculations were carried out for four quinoline alkaloids from the Rutaceae: acridone, acronycine, oligophylidine, and skimmianine, which were stacked atop the DNA base pairs. The structures were optimized using ab initio Hartree-Fock (HF) 3-21G* calculations. These were arranged according to degree of FMO overlap and minimized (MMFF94), followed by single-point ab initio calculations. This study shows that there is no correlation between electronic energies and FMO overlap. In addition, there is no correlation between dipole moment and electronic energy. The overlap of the FMO's of the DNA purine bases and an intercalator cannot be used to predict the orientation the intercalator will adopt. Furthermore, total dipole also cannot be used to predict the preferred orientation of the intercalator.