Electron-driven proton transfer behaviors in oxidative DNA lesion 8-oxoguanine: A computational study

Recent research has highlighted the DNA replicative misinsertion of adenine into 8-oxoguanine (8OG), resulting in the formation of the A-8OG conformation. This misinsertion alters the balance among three mispair structures: A_anti-8OG_syn, A_syn-8OG_anti, and A_anti-8OG_anti. This study reveals the reactive mechanisms involved in excited-state intermolecular proton transfer (ESIPT) and photo-isomerization of A-8OG mispairs. Our findings indicate that the excited-state intermolecular double proton transfer reactions occur along the stepwise reaction path (N∗→SPT∗→DPT∗), and three types of SPT∗ products after photo-isomerizations are found to be stable. Evidence regarding hydrogen bonding parameters and frontier molecular orbitals confirms that the interaction energy of hydrogen bonds, when photo-induced, is enhanced, thus increasing the likelihood of ESIPT reactions. Analysis of absorption spectra and electron density distribution further indicates that electron transfer-driven proton transfer in the excited state also raises the probability of isomerization in A-8OG. Furthermore, the study examines the impact of a uniform electric field on the electronic properties of A-8OG. The findings demonstrate that while the electric field can regulate the interactions of hydrogen bonds, it has minimal influence on electron transfer behavior.