Model studies on a carprofen derivative as dual photosensitizer for thymine dimerization and (6-4) photoproduct repair

Cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts are among the main UV-induced DNA lesions. Both types of damage are mostly repaired in prokaryotes by photolyase enzymes. The repair mechanism of (6-4) photolyases has still not been fully elucidated, but it is assumed that back rearrangement to the oxetane occurs prior to repair. In this work, a non-steroidal anti-inflammatory drug derivative corresponding to the dechlorinated methyl ester of carprofen (namely methyl 2-(carbazol-2-yl)propanoate, PPMe) has been used to achieve the photosensitized cycloreversion of model oxetanes (formally resulting from photo-cycloaddition between benzophenone and 1,3-dimethylthymine or 2'-deoxyuridine), by employing fluorescence spectroscopy, laser flash photolysis, HPLC and NMR. Although PPMe is able to photoinduce the cycloreversion of both oxetones, the fluorescence quenching of PPMe is faster for the 2'-deoxyribose-containing it oxetane; this underlines the importance of the structure in such studies. Moreover, PPMe was shown to photoinduce the formation of thymidine cyclobutane dimers through a triplet-triplet energy transfer from a vibrationally excited state, as suggested by the enhanced PPMe triplet quenching by thymidine with increasing temperature. These results reveal a dual role of PPMe in DNA photosensitization, in that it photoinduces either damage or repair.