Interactions of hydrated divalent metal cations with nucleic acid bases. How to relate the gas phase data to solution situation and binding selectivity in nucleic acids

Binding modes of hydrated Zn2+ and Mg2+ cations to the N7 and O6 positions of guanine have been characterized by state-of-the-art ab initio model calculations. We show how differences in the electronic structure of the cationic complexes, as revealed by gas-phase computations, translate into differences in the biological function of the two studied metals. The thermodynamic driving force of the metal binding process is estimated on the basis of interaction energies and total electronic energies. The computed results unambiguously reveal that the N7 position of guanine exhibits a greater propensity to bind Zn2+ than Mg2+ while both cations have a similar affinity to bind to O6. Contrary to the intuitive expectations, however, the computed data do not suggest any superiority of the N7 inner shell binding mode for Zn2+ compared to the O6 binding. For Mg2+ the O6 inner shell binding mode is favored over the N7 one. The gas-phase data, when properly exrapolated, provide a relevant picture of many (though not all) fundamental aspects of the diversity of cation binding to nucleic acids.