Cation–DNA outer sphere coordination in DNA polymorphism

There are two approaches to describing DNA-ion interactions. The physical approach is an analysis of electrostatic interactions between ions and charges on the DNA molecule. The coordination chemistry approach is a search for modes of direct binding of ions to ionophores of DNA. We study both the inner- and outer sphere coordination of ions by ionophores of the A and C forms of DNA in molecular dynamics simulations in two low-polarity solvents: ethanol-water and methanol-water mixtures. We show that the counterion-DNA outer sphere coordination plays a key role in the experimentally observed conformational polymorphism of the DNA molecule: a transition to the A form in ethanol and to the C form in methanol. We identify the ionophores responsible for the existence of the A- and C-complexes. In both complexes, the ions' inner sphere ligands are mostly water molecules; the ions reside in water clusters. In the ethanol-water mixture, the water clusters are large, the major groove of the A-DNA is filled with water, and all ionophores are accessible to ions. In the methanol-water mixture, the water clusters are small, and a large number of methanol clusters are present near the DNA surface. They interfere with the coordination of ions in one of the ionophores of the major groove and also with other ionophores near phosphates. Therefore, in methanol, the interaction energy of counterions with A-DNA cannot compensate for the repulsion between closely located phosphates. Consequently, the ions fill the more accessible ionophores of the C-complex, converting DNA into the C form.