Photosensitization of thymine nucleobase by benzophenone through energy transfer, hydrogen abstraction and one-electron oxidation

Abstract

In order to understand the mechanism of benzophenone-mediated photosensitization of thymidine, a comparison of the structure of the observed lesions, as well as their respective amounts, has been made with those obtained by photosensitization with menadione. Emphasis is placed on the elucidation of the mechanisms of benzophenone-mediated photosensitization of the thymine moiety of thymidine and thymidylyl-(3′ → 5′)-thymidine (TpT). This is achieved by the quantitative measurement of the main final photoproducts. Further insights into the mechanistic feature are gained by comparing the data obtained on menadione-mediated photosensitization of thymidine. In benzophenone- and menadione-mediated photosensitization of thymidine, 5-(hydroxymethyl)-2′-deoxyuridine (HMdUrd). 5-formyl-2′-deoxyuridine (FordUrd) and the four diastereoisomers of 5,6-dihydroxy-5,6-dihydrothymidine (DOHdThd) are identified and accurately quantified by gas chromatography/mass spectrometry (GC/MS) analysis. The ratio [HMdUrd+FordUrd]/[DOHdThd] is found to be five-fold higher in the case of the benzophenone-mediated photosensitization than in the menadione one. This is strongly indicative that benzophenone is able to abstract a hydrogen from the methyl group of thymine nucleobase. Moreover, the formation of DOHdThd provides evidence for the occurrence of an additional oxidative mechanism of the thymine nucleobase. The thymine base dimerization, observed on the nucleoside model, is quantified on TpT. This provides relevant information about the relative efficiency of the energy-transfer reaction and charge-transfer process.