Unexpected dissociation energetics of the Na+ counterion from GC motifs in DNA hole-migration

Abstract

We present here a theoretical investigation of the electronic and energetic properties of Na⁺GC, a DNA motif bound to a sodium ion (Na⁺) at the N₇ and O₆ sites of guanine (G), and its hole-trapped derivative [Na⁺GC]⁺ using density functional theory calculations. Normally, Na⁺GC has positive dissociation energies along various dissociation channels. However, hole-trapping of the Na⁺GC motif can lead to an unusual energetic phenomenon. Hole-trapping can reduce not only the dissociation barrier by destabilizing the Na⁺GC motif to a metastable state, but also the dissociation energy of the Na⁺⋯N₇/O₆ bond with an unexpected change from a positive to a negative value (61.51 versus −16.18 kcal mol⁻¹). This unexpected negative dissociation energy phenomenon implies that this motif can store energy (∼16 kcal mol⁻¹) in the Na⁺⋯N₇/O₆ bond zone due to hole-trapping. The topological properties of electron densities and the Laplacian values at the bond critical points indicate that this energetic phenomenon mainly originates from additional electrostatic repulsions between two moieties linked via a high-energy bond (Na⁺⋯N₇/O₆). Proton transfer from G induced by hole-trapping can expand the negative dissociation energy zone to both Na⁺⋯N₇/O₆ and Watson–Crick (WC) H-bond zones. Similar phenomena can be observed for the Na⁺ binding at the minor groove. Solvation of the hole-trapped Na⁺GC motif can change the negative dissociation energies by varying degrees, depending on the solvent-binding sites and the polarity of the solvents.