A comparative study to predict regioselectivity, electrophilicity and nucleophilicity with Fukui function and Hirshfeld charge

Abstract

Chemical reactivity properties such as regioselectivity, electrophilicity and nucleophilicity are important chemical concepts, yet their understanding and quantification are still far from being accomplished. Applying density functional theory (DFT) to appreciate these properties is one route to pursue in the literature. In this work, we present a comparative study to benchmark two approaches in DFT to predict regioselectivity, electrophilicity and nucleophilicity: one with the Hirshfeld charge and the other with the Fukui function. We also examine the impact of 15 different ways to compute atomic charges on the performance of their predictions about these chemical reactivity properties. Our results show that the Hirshfeld charge is able to reliably determine regioselectivity and simultaneously accurately quantify both electrophilicity and nucleophilicity. The Fukui function behaves reasonably well for the prediction of electrophilicity but performs poorly for nucleophilicity. Among all other atomic charges examined in this study, it is only the Voronoi deformation density charge that yields the similar result as the Hirshfeld charge. As the first systematic benchmark study in the literature to compare the two available approaches in DFT about reactivity predictions, this work should fill in the needed knowledge gap and provide an impetus for the future development of chemical reactivity theory using DFT language.