Electronic Excited States Responsible for Dimer Formation upon UV Absorption Directly by Thymine Strands: Joint Experimental and Theoretical Study
CNRS, IRAMIS, SPAM, Laboratoire Francis Perrin , URA 2453, 91191 Gif-sur-Yvette, France.Journal of the American Chemical Society (Impact Factor: 12.11). 08/2012; 134(36):14834-45. DOI: 10.1021/ja304069f
The study addresses interconnected issues related to two major types of cycloadditions between adjacent thymines in DNA leading to cyclobutane dimers (T<>Ts) and (6-4) adducts. Experimental results are obtained for the single strand (dT)(20) by steady-state and time-resolved optical spectroscopy, as well as by HPLC coupled to mass spectrometry. Calculations are carried out for the dinucleoside monophosphate in water using the TD-M052X method and including the polarizable continuum model; the reliability of TD-M052X is checked against CASPT2 calculations regarding the behavior of two stacked thymines in the gas phase. It is shown that irradiation at the main absorption band leads to cyclobutane dimers (T<>Ts) and (6-4) adducts via different electronic excited states. T<>Ts are formed via (1)ππ* excitons; [2 + 2] dimerization proceeds along a barrierless path, in line with the constant quantum yield (0.05) with the irradiation wavelength, the contribution of the (3)ππ* state to this reaction being less than 10%. The formation of oxetane, the reaction intermediate leading to (6-4) adducts, occurs via charge transfer excited states involving two stacked thymines, whose fingerprint is detected in the fluorescence spectra; it involves an energy barrier explaining the important decrease in the quantum yield of (6-4) adducts with the irradiation wavelength.
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ABSTRACT: We here report a fully quantum mechanical study of the main photochemical and photophysical decay routes in aqueous solution of Thymine deoxy-dinucleotide (TpT- and TpTNa) and of its analogue locked in C3-endo puckering, characterizing five different representative backbone conformers and discussing the chemical physical effects modulating the yield of the different photoproducts. Our approach is based on Time-Dependent DFT calculations, using the last generation M052X functional, while solvent effects are included by means of the Polarizable Continuum Model. Especially when at least one of the sugar adopts C3-endo puckering a barrierless path on the bright ∏ ∏* excitons leads to the S1/S0 crossing region corresponding to the formation of Cyclobutane Pyrimidine dimer. Charge Transfer excited states involving the transfer of an electron from the 5' Thy towards the 3' Thy are involved in the formation of the oxetane intermediate in the path leading to 6-4 pyrimidine pyrimidinone adducts. A non-negligible energy barrier is associated to this latter pathway, which is possible only when one of the two nucleotides adopts C2-endo puckering. Monomer like decay pathways, involving ∏ ∏* or π ∏* excited states localized on a single bases, are shown to be operative also for loosely stacked bases.
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ABSTRACT: The nature of electronically excited states in DNA is analyzed in detail using a combination of quantum mechanical (QM) semiempirical calculations and molecular dynamics (MD). For this purpose, we consider homogeneous π stacks extracted from the MD trajectory of a poly(A)·poly(T) oligomer. The environment is accounted for within the QM/MM scheme. The effects of structural fluctuations on exciton delocalization and photoinduced charge separation are explored using the quantitative analysis of the electron density in the excited states. We distinguish the effects generated by the vibronic interactions within nucleobases and by the environment of the π stack. While in ideal B-DNA stacks (A-T)(n) singlet excited states are spread over all intrastrand nucleobases, the average exciton length is ∼0.75n, thermal fluctuations decrease considerably the extent of delocalization. The QM/MD model predicts that the excitons in (A-T)(n) stacks are spread over 3 bases (for n = 4 and 6, the average exciton length is found to be 2.6 ± 0.3 and 2.8 ± 0.3, respectively). We show that the main factor reducing the exciton length is the vibronic interactions within nucleobases whereas fluctuations of the π stack environment play a relatively minor role. The oscillator strength of electronic transitions from the ground state to charge-separated states A(k)(+)A(k±1)(-) and T(k)(+)T(k±1)(-) is found to be strong enough to populate directly these states by UV absorption at E = 5.0-5.3 eV. In contrast, the direct formation of interstrand charge transfer states A(i)(+)T(j)(-) is predicted to be unlikely.
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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 (1ππ*(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 1ππ*(PT-CT) excited state and the ground state which likely deactivates the CT excited state via a proton-coupled electron transfer (PCET) mechanism. The 1ππ*(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 1ππ*(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.
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