Influence of the environment on the specificity of the Mg(II) binding to uracil

Interactions of uracil with the Mg(2+) ion were studied theoretically in the gas phase and in solution. The bare Mg(2+) prefers bidentate N-C═O binding sites stabilizing rare keto-enol forms of the base. Hydration and/or phosphate binding of the Mg(2+) ion shield its positive charge, which leads to preference of monodentate binding to the oxygen keto atoms, shifting fully the equilibrium between the tautomers back toward the canonical diketo tautomer. In solution, a direct inner-sphere metal binding to uracil is not clearly advantageous compared to the outer-sphere metal binding. Similar trends were also obtained for the Ca(2+) ion. Results are supported by the natural bond orbital (NBO) and atoms in molecule (AIM) analyses and the combined extended transition-state energy decomposition analysis and natural orbitals for chemical valence (ETS-NOCV).