The (6-4) Dimeric Lesion as a DNA Photosensitizer

[EN] Based on our previous investigations into the photophysical properties of the 5-methyl-2-pyrimidone (Pyo) chromophore, we now extend our studies to the photobehavior of the dimeric (6-4) thymine photoproducts (6-4 PP) to evaluate their capability to act as instrinsic DNA photosensitizers. The lesion presents significant absorption in the UVB/UVA region, weak fluorescence emission, a singlet-excited-state energy of approximately 351 kJ mol(-1), and a triplet-excited-state energy of 297 kJ mol(-1). Its triplet transient absorption has a maximum at 420-440 nm, a lifetime of around 7 mu s, and a high formation quantum yield, Phi(ISC) = 0.86. This species is efficiently quenched by thymidine. Its DNA photosensitizing properties are demonstrated by a series of experiments run on a pBR322 plasmid. The lesion photoinduces both single-strand breaks and the formation of cyclobutane thymine dimers. Altogether, these results show that, the substitution of the pyrimidone ring at C4 by a 5-hydroxy-5,6-dihydrothymine does not cancel out the photosensitization properties of the chromophore.Spanish Government (CTQ2015-70164-P, RIRAAF RETICS RD12/0013/0009, Prometeo II program, Severo Ochoa program/SEV-2012-0267 and JAE-Predoc 2011-00740 to V. V.-C.) is gratefully acknowledged.Vendrell Criado, V.; Rodríguez Muñiz, GM.; Lhiaubet ., VL.; Cuquerella Alabort, MC.; Miranda Alonso, MÁ. (2016). The (6-4) Dimeric Lesion as a DNA Photosensitizer. ChemPhysChem (Online). 17(13):1979-1982. doi:10.1002/cphc.201600154S19791982171