Photosensitization of Thymine Nucleobase by Benzophenone Derivatives as Models for Photoinduced DNA Damage: Paterno−Büchi vs Energy and Electron Transfer Processes

Abstract

Time-resolved and product studies have shown that there is a strong interaction between drugs containing the benzophenone chromophore and the free thymidine nucleoside. In quantitative terms, such an interaction is stronger for the lowest lying npi* triplet states (S-ketoprofen) than for mixed npi*-pipi* triplets (fenofibrate and fenofibric acid), as indicated by the quenching rate constants. This is consistent with a Paterno-Büchi photoreaction, where the initial step is the formation of a new bond between the excited carbonyl oxygen and one of the thymine olefinic carbons. Actually, oxetanes are obtained as photoproducts when benzophenone is irradiated in the presence of thymidine. Hence, triplet-triplet energy transfer resulting in formation of cyclobutane pyrimidine dimers, which would be thermodynamically disfavored, does not seem to play a major role. However, in DNA, the contribution of energy transfer could be higher, due to the lower energy of the thymine triplet in the biomacromolecule. These results are discussed in connection with the observed DNA damage upon photosensitization with ketoprofen, fenofibrate, and fenofibric acid.