A Quantum Chemical Study of Cu ²⁺ Interacting with Guanine-Cytosine Base Pair. Electrostatic and Oxidative Effects on Intermolecular Proton-Transfer Processes

The influence of metal cations (M = Cu +, Ca 2+ and Cu 2+) 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 Cu 2+ the reaction can still be easily produced, especially for certain local environments of the metal cation for which Cu 2+ induces the oxidation of guanine. Therefore, the ability of Cu 2+ to oxidize guanine turns out to be a key factor for this mutagenic process.