INSIGHT INTO MECHANISM OF FORMATION OF C8 ADDUCTS IN CARCINOGENIC REACTIONS OF ARYLNITRENIUM IONS WITH PURINE NUCLEOSIDES II: AB INITIO, DFT, AND ABEEM/MM-MD SIMULATION STUDIES OF CHEMICAL REACTIONS CONCERNING N9-SUBSTITUTED PURINE BASES WITH 4-BIPHENYLYLNITRENIUM ION

Abstract

Theoretical insight into the mechanism of C8 adducts formation in a series of complicated carcinogenic reactions has been provided in a previous work. However, two important issues involved in this mechanism still need to be elucidated in detail. Hence, in this paper, we first present a new theoretical model to study the direct formation mechanism of C8 adduct. It is found that this model can well reflect the actual interactions in the real carcinogenic reactions. Thus, a better theoretical model to simulate other properties of these complicated reactions is found using ab initio and density functional theory (DFT) methods. Second, we simulate the formation process of C8 adduct in this new theoretical model using ABEEM/MM-MD method. According to the MD study, we approve that the higher aqueous-phase activation energy for transition state in this kind of reaction contributes to weaker interactions between central sites of reaction and water compared with those for reactants. This study once more supports the mechanism of formation of C8 adducts in the actual carcinogenic reactions where arylnitrenium ions directly attack at C8 positions of nucleoside bases in DNA.