Multiple Electronic and Structural Factors Control Cyclobutane Pyrimidine Dimer and 6–4 Thymine–Thymine Photodimerization in a DNA Duplex
2017; Wiley; Volume: 23; Issue: 60 Linguagem: Inglês
10.1002/chem.201703237
ISSN1521-3765
AutoresIrene Conti, Lara Martínez‐Fernández, Luciana Esposito, Siegfried Höfinger, Artur Nenov, Marco Garavelli, Roberto Improta,
Tópico(s)Photochromic and Fluorescence Chemistry
ResumoAbstract 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 T 3 and a 5′‐T→3′‐T charge transfer for CPD and oxetane formation, respectively, thus calling for specific electronic constraints.
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