Ion-pairing equilibria and kinetics of dimethyl phosphate: A model for counter-ion binding to the phosphate backbone of nucleic acids

Dimethyl phosphate (DMP–) is the simplest model ion to assess ion-pairing phenomena between metal ions and the phosphate backbone of nucleic acids. Yet, the equilibria and dynamics of ion binding to DMP– have not been fully uncovered. Here, we study the interaction of DMP– with different cations and water in aqueous solutions of NaDMP using dielectric relaxation and nuclear magnetic resonance spectroscopies. We find DMP– to be weakly hydrated and weakly associated with Na+ in the absence of added salt. Upon addition of NaCl, MgCl2, or CaCl2 to solutions of NaDMP, we detect the formation of solvent-shared (NaDMP0) and contact (MgDMP+, CaDMP+) ion-pairs; the degree of ion association is 20–27 % at 2:1 salt:DMP molar ratio for the bivalent ions. Comparison to literature results suggests the formation constant of MgDMP+ to be a good estimate for the binding of Mg2+ to RNA. From the concentration dependence of the rotational relaxation time of the ion-pairs, we find ion-pair dissociation rates to follow the order Mg2+ ≪ Ca2+ < Na+. Strikingly, our data suggest that the overall ion-pair dissociation dynamics are governed by an ion-pair metathesis reaction, which provides a different pathway for the binding of ions by DMP–