Theoretical Research In Nucleic Acid Damage Induced By Hydroxyl Radicals(OH·) And Electron Transfer

Essential genetic information, necessary to maintain normal life activities for allorganisms, is stored in nucleic acid. Endogenous and exogenous sources (such as ionizingradiation, UV radiation, etc) may cause DNA damage, which, if unrepaired, may result inmutations or cell death. In nearly recent two decades, many groups focus on themechanisms of DNA damage induced by reactive oxygen species (ROS) and electrontransfer.In this paper, we overview the mechanisms of DNA damage induced by hydrogenabstraction, electron addition, ionization of DNA bases, hydrogen atom and hydride anionadditions. Then we successfully develop a first-principle method to predict the redoxpotentials of the aromatic compounds in aqueous solution, and obtain a set of redoxpotentials of DNA nucleobases and the metabolites using this method. Based on the results,disscussions are made about connections between the redox potentials and charge/electrontransfer in DNA. Furthermore, six possible hydrogen abstraction pathways for A-T base pairattacked by the hydroxyl radical have been investigated at the B3LYP/DZP++level oftheory.Main innovative points are as follows: On the methodology, we develop afirst-principles method for predicting redox potentials of nucleobases and the metabolites inaqueous solution. On the research object, A-T base pair is selected as the model compoundsduring the study of DNA damage induced by hydroxyl radical; On the application prospectof this subject, predictions on the mechanism of DNA damage play an important role indesigning new high detection sensitivity biosensor.