A theoretical investigation of the influence of divalent metal cation binding on the nucleic base pairing is presented. The investigation includes a variety of theoretical analyses, which include electron topology properties, electrostatic properties, natural bond orbital analysis, and harmonic vibrational analysis. All calculations reported here involve pentahydrated Mg2+ cation interacting with the base pairs GC, GG, and AU and their complexes formed by the corresponding purine nucleotide. The present calculations provide an important physicochemical insight into metal cation-base interactions. Particularly, they allow us to explain the striking difference in the cation-induced enhancement of base pairing observed in G-containing base pairs compared to A-containing base pairs. Indeed, the results also reveal the active role of hydrating water molecules in modulating the binding of the cation through a specific network of hydrogen bonds with both the purine and the phosphate group. The results can be valuable for gaining further insight into the effect of metal cation binding to the N7 site of guanine and adenine in physiological DNA.