title: Excited state proton-coupled electron transfer in 8-oxoG-C and 8-oxoG-A base pairs: a time dependent density functional theory (TD-DFT) study.
abstract: In a recent experiment, the repair efficiency of DNA thymine cyclobutane dimers (T<>T) on UV excitation of 8-oxoG base paired either to C or A was reported. An electron transfer mechanism from an excited charge transfer state of 8-oxoG-C (or 8-oxoG-A) to T<>T was proposed and 8-oxoG-A was found to be 2-3 times more efficient than 8-oxoG-C in repair of T<>T. Intra base pair proton transfer (PT) in charge transfer (CT) excited states of the base pairs was proposed to quench the excited state and prevent T<>T repair. In this work, we investigate this process with TD-DFT calculations of the excited states of 8-oxoG-C and 8-oxoG-A base pairs in the Watson-Crick and Hoogsteen base pairs using long-range corrected density functional, ωB97XD/6-31G* method. Our gas phase calculations showed that CT excited state ((1)ππ*(CT)) of 8-oxoG-C appears at lower energy than the 8-oxoG-A. For 8-oxoG-C, TD-DFT calculations show the presence of a conical intersection (CI) between the lowest (1)ππ*(PT-CT) excited state and the ground state which likely deactivates the CT excited state via a proton-coupled electron transfer (PCET) mechanism. The (1)ππ*(PT-CT) excited state of 8-oxoG-A base pair lies at higher energy and its crossing with ground state is inhibited because of a high energy gap between (1)ππ*(PT-CT) excited state and ground state. Thus the gas phase calculations suggest the 8-oxoG-A would have longer excited state lifetimes. When the effect of solvation is included using the PCM model, both 8-oxoG-A and 8-oxoG-C show large energy gaps between the ground state and both the excited CT and PT-CT states and suggest little difference would be found between the two base pairs in repair of the T<>T lesion. However, in the FC region the solvent effect is greatly diminished owing to the slow dielectric response time and smaller gaps would be expected.
authors.affiliation: Department of Chemistry, Oakland University, Rochester, Michigan 48309, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Michael D
authors.initials: MD
authors.lastname: Sevilla
mesh_terms: D000225:Adenine / Q000737:chemistry*; D020029:Base Pairing; D003596:Cytosine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D004583:Electrons; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D011522:Protons; D011789:Quantum Theory
chemical_list: D011522:Protons; C024829:8-hydroxyguanine; D006147:Guanine; D003596:Cytosine; D004247:DNA; D000225:Adenine