Evidence of direct formation of C8 adducts in carcinogenic reactions of arylnitrenium ions with purine nucleosides: Theoretical study of C8 deprotonation process

Theoretical insight into the formation mechanism of C8 adducts in a series of complicated carcinogenic reactions has been provided in some previous works. However, the actual C8 deprotonation process involved in this mechanism requires further detailed elucidation. In this paper, we first present the structural features of a proton wire related to the C8 deprotonation process in terms of ABEEM/MM-MD simulations. Then, on the basis of MD simulations, appropriate theoretical models are constructed to study the C8 deprotonation process, and the energetics of the deprotonation process are determined by employing ab initio and DFT methods. The obtained results agree with experimental observations. This study supports the mechanism of formation of C8 adducts in actual carcinogenic reactions, where arylnitrenium ions directly attack at the C8 positions of nucleoside bases in DNA.