An Exploration of the Transformation of the 8‐Oxo‐7,8‐Dihydroguanine Radical Cation to Protonated 2‐Amino‐5‐Hydroxy‐7,9‐Dihydropurine‐6,8‐Dione in a Base Pair

A theoretical investigation was performed to disclose the transformation mechanism of 8-oxo-7,8-dihydroguanine radical cation (8-oxoG⋅+ ) to protonated 2-amino-5-hydroxy-7,9-dihydropurine-6,8-dione (5-OH-8-oxoG) in base pair. The energy profiles for three possible pathways of the events were mapped. It is shown that direct loss of H7 from base paired 8-oxoG⋅+ is the only energetically favorable pathway to generate neutral radical, 8-oxoG(-H7)⋅. Further oxidation of 8-oxoG(-H7)⋅ : C to 8-oxoG(-H7)+ : C is exothermic. However, the 8-oxoG(-H7)+ : C deprotonation from all possible active sites is infeasible, indicating the inaccessible second proton loss and the lack of essential intermediate 2-amino-7,9-dihydropurine-6,8-dione (8-oxoGOX ). This makes 8-oxoG(-H7)+ act as the precursor of hydration leading to the generation of protonated 5-HO-8-oxoG by stepwise fashion in base pair, which would initiate the step down guanidinohydantoin (Gh) pathway. These results clearly specify the structure-dependent transformation for 8-oxoG⋅+ and verify the emergence of protonated 5-HO-8-oxoG in base pair.