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The chemical fate of radical intermediates is relevant to understand the biological effects of radiation and to explain formation of DNA lesions. A direct approach to selectively generate the putative reactive intermediates is based on the irradiation of photolabile precursors. But, to date, radical formation and reactivity have only been studied in aqueous media, which do not completely mimic the micro environment provided by the DNA structure and its complexes with proteins. Thus, it is also important to evaluate the photogeneration of nucleoside-based radicals in nonaqueous media. The attention here is focused on the independent generation of 5,6-dihydropyrimidin-5-yl radicals in organic solvent through the synthesis of new lipophilic tert-butyl ketone precursors. Formation of 5,6-dihydro-2'-deoxyuridin-S-yl and 5,6-dihydrothymidin-5-yl radicals has first been confirmed by using a new nitroxide-derived profluorescent radical trap. Further evidence has been obtained by nanosecond laser flash photolysis through detection of long-lived transients. Finally, the experimental data are corroborated by multiconfigurational ab initio CASPT2//CASSCF methodology., Spanish Government (CTQ2012-32621, CTQ2015-70164-P, CTQ2014-58624-P, RIRAAF RETICS RD12/0013/0009, Severo Ochoa program/SEV-2012-0267, Maria de Maetzu program/MDM-2015-0538, BES-2011-048326 and BES-2013-066566, JCI-2012-13431) and Generalitat Valenciana (Prometeo 11/2013/005 and GV2015-057) are gratefully acknowledged. Dr. M. Luisa Marin is also acknowledged for her help during laser flash photolysis experiments.

[EN] Imatinib is a synthetic tyrosinase inhibitor that is employed for the treatment of some kinds of human cancer. This drug has a low phototoxicity towards DNA, but its pyridylpyrimidine (1) fragment by itself exhibits significant phototoxicitiy. The intrinsic mechanism that leads to the enhanced photosafety of Imatinib is not yet known. Here, the properties of the excited state and interchromophoric interactions of Imatinib have been explored by using ultrafast laser flash photolysis and agarose electrophoresis studies. An intramolecular charge separation was directly observed for the irradiated Imatinib, which accounts for the relaxation of its excited state. An anionic form of pyridylpyrimidine (1) was deduced from the results of time-resolved resonance Raman spectra and by quenching experimental studies on compound 1 and diaminotoluene. In contrast, compound 1 efficiently transformed into triplet excited states with a long lifetime, which explained the phototoxicity associated with this fragment. This work provides insight into how to design drugs with lower phototoxicitiy or improved photostability by using interchromophoric interactions., This work was supported by Natural Science Foundation of China (21773151) and Shantou University Initial Funding (NTF16010). The Support from the Hong Kong Research Grants Council grants GRF 17307916, AoE/P-03/08, SEG HKU/07, The University of Hong Kong Development Fund 2013-2014 project "New Ultrafast Spectroscopy Experiments for Shared Facilities", the Spanish Government (CTQ2015-70164-P and BES-2013-066566) are also acknowledged.

[EN] In this work, the attention is focused on UVA-photosensitized reactions triggered by a DNA chromophore-containing lesion, namely 5-formyluracil. This is a major oxidatively generated lesion that exhibits an enhanced light absorption in the UVB-UVA region. The mechanistic study combining photochemical and photobiological techniques shows that irradiation of S-formyluracil leads to a triplet excited state capable of sensitizing formation of cyclobutane pyrimidine dimers in DNA via a triplet-triplet energy transfer. This demonstrates for the first time that oxidatively generated DNA damage can behave as an intrinsic sensitizer and result in an important extension of the active fraction of the solar spectrum with photocarcinogenic potential. Overall, this raises the question of an aggravated photomutagenicity of the 5-formyluracil lesion., The present work was supported by Spanish Government (CTQ2015-70164-P, Severo Ochoa program/SEV-2012-0267, BES-2013-066566, CSIC 2016801007), Instituto de Salud Carlos III (RD16/0006/0030, FIS PI16/01877), Generalitat Valenciana (Prometeo/2017/075).

[EN] Using a sunscreen-based photocage, we have demonstrated that it is possible to prevent photodegradation of a bioactive compound and to achieve its controlled photorelease. The concept has been proven linking avobenzone, one of the most important UVA blockers, to ketoprofen, which is a representative example of a photosensitive drug., Spanish Government (CTQ2015-70164-P, RIRAAF RETICS RD12/0013/0009, Severo Ochoa program/SEV-2012-0267 and BES-2013-066566), Generalitat Valenciana (Prometeo II/2013/005) and VLC/Campus Microcluster "Interacciones Luz-Farmaco en Sistemas Biologicos y Reacciones Adversas'' are gratefully acknowledged.