The double-proton-transfer reaction of the isolated guanine-cytosine (GC) base pair and four DNA trimers with different nucleobase sequences (dATGCAT, dGCGCGC, dTAGCTA, and dCGGCCG) are studied by quantum mechanical calculations using ONIOM(M06-2X/6-31G*:PM3). Proton-transfer patterns, energy and structural properties are analyzed to gain insight into the double-proton-transfer mechanism with consideration to environmental factors. In the gas phase, a stepwise mechanism is found for the dCGGCCG trimer, and a concerted mechanism is found in the other four models. The computational results demonstrate that electrostatic interaction of the peripheral and middle base pairs have a pronounced effect on double-proton-transfer pattern of GC base pairs. The structures with dATGCAT and dGCGCGC sequences facilitate H4a proton transfer and those with dTAGCTA and dCGGCCG sequence facilitate H1 proton transfer. The high proton affinity of cytosine at N3 facilitates H1 proton transfer. In aqueous solution, electrostatic interactions are reduced and the products of single-proton-transfer in the stepwise mechanism are stabilized. This results in a stepwise transfer pattern becoming favorable. Solvent effects favor the single-proton-transfer reaction more than gas phase conditions, but increase the reaction energy of double-proton-transfer.

The effects of the first hydration shell and the bulk solvation effects on the proton-transfer processes of guanine-cytosine (GC) and adenine-thymine (AT) base pairs are studied based on density functional theory, using the B3LYP method and DZP++ basis set. The proton-transfer mechanisms of the GC and AT base pairs in bulk solvation are first single-proton transfer (SPT1) and stepwise double-proton transfer (DPT). When only the first hydration shell surrounded by five water molecules (GC • 5H2O, AT • 5H2O), or both the first hydration shell and bulk solvation effects through polarizable continuum model (PCM) (GC•5H2O+PCM, AT•5H2O+PCM) are considered, only the first single-proton-transfer mechanism (SPT1) is found. The proton-transfer activation energies of the GC and the AT base pairs show that the majority of the hydration effects come from the first hydration shell through hydrogen-bond interactions, therefore the first hydration shell greatly influences the base pair structures and proton-transfer mechanism.