Reductive Photocycloreversion of Cyclobutane Dimers Triggered by Guanines

The quest for simplesystems achieving the photoreductive splittingof four-membered ring compounds is a matter of interest not only inorganic chemistry but also in biochemistry to mimic the activity ofDNA photorepair enzymes. In this context, 8-oxoguanine, the main oxidativelygenerated lesion of guanine, has been shown to act as an intrinsicphotoreductant by transferring an electron to bipyrimidine lesionsand provoking their cycloreversion. But, in spite of appropriate photoredoxproperties, the capacity of guanine to repair cyclobutane pyrimidinedimer is not clearly established. Here, dyads containing the cyclobutanethymine dimer and guanine or 8-oxoguanine are synthesized, and theirphotoreactivities are compared. In both cases, the splitting of thering takes place, leading to the formation of thymine, with a quantumyield 3.5 times lower than that for the guanine derivative. This resultis in agreement with the more favored thermodynamics determined forthe oxidized lesion. In addition, quantum chemistry calculations andmolecular dynamics simulations are carried out to rationalize thecrucial aspects of the overall cyclobutane thymine dimer photoreductiverepair triggered by the nucleobase and its main lesion.