Intermolecular proton-transfer processes in the Watson & Crick adenine-thymine Cu+ and Cu2+ cationized base pairs have been studied using the density functional theory (DFT) methods. Cationized systems subject to study are those resulting from cation coordination to the main basic sites of the base pair, N7 and N3 of adenine and O2 of thymine. For Cu+ coordinated to N7 or N3 of adenine, only the double proton-transferred product is found to be stable, similarly to the neutral system. However, when Cu+ interacts with thymine, through the O2 carbonyl atom, the single proton transfer from thymine to adenine becomes thermodynamically spontaneous, and thus rare forms of the DNA bases may spontaneously appear. For Cu 2+ cation, important effects on proton-transfer processes appear due to oxidation of the base pair, which stabilizes the different single proton-transfer products. Results for hydrated systems show that the presence of the water molecules interacting with the metal cation (and their mode of coordination) can strongly influence the ability of Cu2+ to induce oxidation on the base pair. © 2008 American Chemical Society.