Predicting DNA–intercalator binding: the development of an arene–arene stacking parameter from SAPT analysis of benzenesubstituted benzene complexes

摘要

A series of substituted naphthalimides were synthesized and intercalated into the DNA sequence d(GCGCGCGC)2, and an experimental ΔT_m value was obtained. Two-parameter QSAR analyses were performed to generate a theoretical ΔT_m value. Although by no means exhaustive in terms of parameter selection, the correlations did not yield statistics that indicated the models met the threshold for significance at the 95% confidence level. Rather than continue with an exhaustive search of all possible QSAR parameters, a one-parameter QSAR analysis was performed utilizing a novel arene–arene stacking parameter, designated Ππ, developed from Symmetry-Adapted Perturbation Theory (SAPT) energy decomposition studies of calculated benzene-substituted benzene dimer binding energies. The QSAR analysis using the Π~π stacking parameter yielded statistics suggesting the model was significant at the 95% confidence level. The approach of developing a novel QSAR parameter via SAPT calculations, rather than exhaustively searching all traditional QSAR parameters, is presented both as a new approach for QSAR studies and as a unique application of SAPT.