A Base-Sugar−Phosphate Three-Layer ONIOM Model for Cation Binding: Relative Binding Affinities of Alkali Metal Ions for Phosphate Anion in DNA

Abstract

A three-layer ONIOM approach was used to study the interactions of hydrated alkali metal ions such as Li+, Na+, and K+ with a DNA fragment containing two phosphate groups, three sugar units, and a G••C base pair modeled in the anion and dianion states. Among the three metal-binding combinations studied herein (outer-sphere, inner-sphere monodentate, and inner-sphere bidentate), the outer-sphere binding mode showed the highest binding energy (BE) for hydrated Li+ ions (103.1 kcal/mol) while the hydrated Na+ and K+ ions preferred the inner-sphere monodentate binding modes to the phosphate group of the anionic DNA fragment (BE = 87.9 and 98.2 kcal/mol for Na+ and K+, respectively). These data on the binding mechanisms of Li+, Na+, and K+ ions and the higher binding affinity of Li+ ions compared to Na+ and K+ ions in the anion model system of DNA are in good agreement with the previous experimental findings. On the other hand, in the dianion state, Li+ preferred inner-sphere monodentate, whereas Na+ and K+ ions preferred the outer-sphere structures. The neutral anion model ion revealed a more realistic picture of DNA−alkali metal ion interactions compared to the non-neutral dianion model systems.