Theoretical Studies on Photoisomerizations of (6−4) and Dewar Photolesions in DNA

Abstract

The (6-4) photoproduct ((6-4) PP) is one of the main lesions in UV-induced DNA damage. The (6-4) PP and its valence isomer Dewar photoproduct (Dewar PP) can have a great threat of mutation and cancer but gained much less attention to date. In this study, with density functional theory (DFT) and the complete active space self-consistent field (CASSCF) methods, the photoisomerization processes between the (6-4) PP and the Dewar PP in the gas phase, the aqueous solution, and the photolyase have been carefully examined. Noticeably, the solvent effect is treated with the CASPT2//CASSCF/Amber (QM/MM) method. Our calculations show that the conical intersection (CI) points play a crucial role in the photoisomerization reaction between the (6-4) PP and the Dewar PP in the gas and the aqueous solution. The ultrafast internal conversion between the S(2) ((1)ππ*) and the S(0) states via a distorted intersection point is found to be responsible for the formation of the Dewar PP lesion at 313 nm, as observed experimentally. For the reversed isomeric process, two channels involving the "dark" excited states have been identified. In addition to the above passages, in the photolyase, a new electron-injection isomerization process as an efficient way for the photorepair of the Dewar PP is revealed.

The Excited‐State Decay of 1‐Methyl‐2(1H)‐pyrimidinone is an Activated Process

“…[15] Light absorption of the pyrimidinone moiety induces a secondary photochemical reaction-the formation of a Dewar valence isomer ( Figure 1). [9,[16][17][18] Due to the higher spectral intensity mentioned above, and a rather high quantum yield of % 0.02, most (6-4) lesions eventually transform into Dewar lesions under solar illumination. [9] As part of an effort to study the Dewar formation, herein we report the photophysical properties of the pyrimidinone chromophore.…”

“…For 5-methyl-2-(1H)-pyrimidinone the conical intersection between the primarily excited pp* state and the ground state was predicted to lie 2300-3400 cm À1 above the pp* minimum. [20] Further, a very recent ab initio study [17] on the pyrimidinone chromophore in the (6-4) lesion predicts an energy difference of % 2000 cm…”

Quantum-chemical investigation of the 1-methylthymine dimer photoproduct: Pyrimidine-(6-4)-pyrimidone adduct

“…1 This fast relaxation prevents the creation of UV damage. [10][11][12][13] The most frequent photoreaction of nucleic acids is an intra-1038 RISTIĆ, PETKOVIĆ and ETINSKI strand pyrimidine dimerization. [2][3][4][5] Recent theoretical work [6][7][8] and supersonic jet experiments 4 have shown that this dark state is the T 1 state.…”

Repair of DNA Dewar Photoproduct to (6-4) Photoproduct in (6-4) Photolyase

“…Our previous work showed that the isomerization from T(dew)T to T(6-4)T in the neutral ground state has a very high barrier (about 30 kcal/mol), while it is sharply reduced to 15 kcal/ mol when one electron is injected. 21 In the current study, several enzymatic repair pathways are studied by the density functional theory method. From our calculations, the rearrangement of the Dewar lesions into the corresponding (6-4) lesions with electron injection was validated as the most efficient repair pathway.…”