Multiple Electronic and Structural Factors Control Cyclobutane Pyrimidine Dimer and 6-4 Thymine-Thymine Photodimerization in a DNA Duplex

Abstract : The T–T photodimerization paths leading to the formation of cyclobutane pyrimidine dimer (CPD) and 6–4 pyrimidine pyrimidone (64-PP), the two main DNA photolesions, have been resolved for a T–T step in a DNA duplex by two complementary state-of-the-art quantum mechanical approaches: QM(CASPT2//CASSCF)/MM and TD-DFT/PCM. Based on the analysis of several different representative structures, we define a new-ensemble of cooperating geometrical and electronic factors (besides the distance between the reacting bonds) ruling T–T photodimerization in DNA. CPD is formed by a barrierless path on an exciton state delocalized over the two bases. Large interbase stacking and shift values, together with a small pseudorotation phase angle for T at the 3′-end, favor this reaction. The oxetane intermediate, leading to a 64-PP adduct, is formed on a singlet T→T charge-transfer state and is favored by a large interbase angle and slide values. A small energy barrier (<0.3 eV) is associated to this path, likely contributing to the smaller quantum yield observed for this process. Eventually, a clear directionality is always shown by the electronic excitation characterizing the singlet photoactive state driving the photodimerization process: an exciton that is more localized on T3 and a 5′-T→3′-T charge transfer for CPD and oxetane formation, respectively, thus calling for specific electronic constraints.
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Submitted on : Wednesday, December 20, 2017 - 2:25:29 PM
Last modification on : Thursday, February 7, 2019 - 5:12:28 PM

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Irene Conti, Lara Martinez-Fernandez, Luciana Esposito, Siegfried Hofinger, Artur Nenov, et al.. Multiple Electronic and Structural Factors Control Cyclobutane Pyrimidine Dimer and 6-4 Thymine-Thymine Photodimerization in a DNA Duplex. Chemistry - A European Journal, Wiley-VCH Verlag, 2017, 23 (60), pp.15177 - 15188. ⟨10.1002/chem.201703237⟩. ⟨cea-01668979⟩

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