Repair of a Dimeric Azetidine Related to the Thymine–Cytosine (6‐4) Photoproduct by Electron Transfer Photoreduction

Abstract

Abstract:Photolyases are intriguing enzymes that take advantage of sunlight to restore lesions like cyclobutane pyrimidine dimers or (6-4) photoproducts. In this work, the attention is focused on the photoreductive process responsible for splitting of the azetidine ring proposed to occur during (6-4) photoproduct repair at thymine-cytosine sequence. A model compound formed by photocycloaddition between thymine and 6-azauracil has been designed to mimic the elusive azetidine intermediate. The photoinduced electron transfer process has been investigated by means of steady-state and time-resolved fluorescence using photosensitizers with oxidation potentials in the singlet excited state ranging from -3.3 to -2.1 V vs SCE. Azetidine ring splitting and recovery of "repaired" bases has been proven by HPLC analysis.

Experimental and Theoretical Study on the Cycloreversion of a Nucleobase‐Derived Azetidine by Photoinduced Electron Transfer

“…As shown in Figure , under these conditions, the azetidine was split to give rise to the dyad azaU m ‐T m . By contrast, with the photoreductive version of the reaction, the quantitative formation of azaU m ‐T m was not observed (Figure , inset). This can be attributed to further oxidation of the nucleobases by DCN, leading to the formation of secondary products.…”

“…Experiments with photoreductants 1‐MN and CHRY were performed by using T m <>T m as the accepting moiety, and compared with those reported for AZT m (Table ) . For the photo‐oxidants DCN and DCA, new experiments were performed for both AZT m and T m <>T m .…”

“… and ). By contrast, ring opening of AZT m to regenerate the native dyad, azaU m ‐T m , has only been achieved in the presence of electron donors, such as N , N , N ′, N ′‐tetramethyl‐1,4‐phenylenediamine (TMPD) . Hence, photo‐oxidation of AZT m was attempted in the presence of DCN as the electron acceptor and analyzed by HPLC to determine the obtained photoproducts.…”

“…To interpret the excited‐state quenching of Phs by AZT m , four Phs with significantly different redox properties of the singlet excited state were chosen to perform a quantum‐chemistry determination of the photoreduction and photo‐oxidation energetics: 1‐MN and DCN (used in the experiments detailed above), together with TMPD and cyanonaphthalene (CNN), employed in previous works ,. Singlet‐excited‐state redox potentials of E *=−2.5, 2.4, −3.3, and 1.4 V versus Ag/AgCl were obtained, respectively.…”

“…In a previous communication, the photoinduced reductive cycloreversion of an azetidine derivative was reported for the first time . This was achieved by using a stable azabipyrimidinic azetidine (AZT m , Scheme ) as a model for the short‐lived intermediate proposed for the repair of (6‐4) photoproducts at TC sequences.…”