DFT STUDY ON THE MECHANISM OF DNA DAMAGE CAUSED BY THE ISOMERIZATION OF DNA PURINE BASE

The mechanism of DNA damage caused by the isomerization of purine base is studied with density functional theory calculations at the B3LYP/6-311+G(d,p) level. The transition states of all the isomerizations are obtained, and the intrinsic reaction coordinate (IRC) analyses are performed to identify these transition states further. The isomerizations of purine bases can be classified into two types. The first is the hydrogen transfer between atoms, whose transition state includes a four-member ring. The second is the bond N-H rotation about the double bond N=C, and the plane CNH is perpendicular to the molecular plane in its transition state. The hydrogen transfer has higher reaction potential barrier, larger tunnel effect, and smaller equilibrium constant and rate constant than that of the N-H rotation. Effects of the hydration are considered in the framework of the polarizable continuum model (PCM) in SCRF method at the B3LYP/6-311+G(d,p) level. The isomerizations which result in the configuration changes of purine base and bring directly the DNA damage are endothermic and thermodynamic nonspontaneous processes. The probability of DNA damage caused by the guanine isomerization is larger than that by adenine.