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 T3and a 5′-T→3′-T charge transfer for CPD and oxetane formation, respectively, thus calling for specific electronic constraints.

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

Conti, Irene;Nenov, Artur;Garavelli, Marco;
2017

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 T3and a 5′-T→3′-T charge transfer for CPD and oxetane formation, respectively, thus calling for specific electronic constraints.
2017
Conti, Irene; Martã­nez-fernã¡ndez, Lara; Esposito, Luciana; Hofinger, Siegfried; Nenov, Artur; Garavelli, Marco; Improta, Roberto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/610694
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