Radical cation transfer in a guanine pair: an insight to the G-quadruplex structure role using constrained DFT/MM

Abstract

DNA G-Quadruplex is highly sensitive to oxidation as their structures include \(\pi\)-stacked guanine quartets allowing fast hole transfer between the nucleobases. These transfers can be described using vertical energy gap and electronic coupling between the different diabatic states at play in a guanine pair. Using classical molecular dynamics simulation and the constrained DFT/MM implementation in deMon2k, we determine these quantities for all the interacting guanine pairs of six G-quadruplex structures including one to four quartets and corresponding to different DNA folding. We then described an uni-directional transfer within a quartet, with high electronic coupling and vertical energy gap values, which contrasts with the hole transfer between \(\pi\)-stacked guanine, bi-directional and corresponding to smaller charge transfer parameters. The influence of the geometrical parameters on the electronic coupling is explored, while the external or internal position of the guanine may impact its oxidation probability according to the vertical energy gaps.