The influence of metal cations (M = Cu+, Ca2+ and Cu2+) coordinated to N-7 of guanine on the intermolecular proton-transfer reaction in guanine-cytosine base pair has been analyzed using the B3LYP density functional approach. Gas phase metal cation interaction stabilizes the ion pair structure derived from the N-1-N-3 single-proton-transfer reaction, the effects being more pronounced for the divalent cations than for the monovalent one. For Cu(2+)GC the reaction is largely favored due to both electrostatic and oxidative effects. Hydration of the metal cation disfavors the reaction due to the screening of electrostatic effects. However, for Cull the reaction can still be easily produced, especially for certain local environments of the metal cation for which Cu2+ induces the oxidation of guanine. Therefore, the ability of Cull to oxidize guanine turns out to be a key factor for this mutagenic process.