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

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.