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Photosensitization by drugs is a problem of increasing importance in modern life. This phenomenon occurs when a chemical substance in the skin is exposed to sunlight. Photosensitizing drugs are reported to cause severe skin dermatitis, and indeed, it is generally advised to avoid sunbathing and to apply sunscreen. In this context, the nonsteroidal anti-inflammatory drug (NSAID) diclofenac is a photosensitive drug, especially when administered in topical form. In this work, efforts have been made to design and study an innovative pro-drug/pro-filter system containing diclofenac and the UVA filter avobenzone in order to develop a safer use of this topical drug. The design is based on the presence of a well-established photoremovable phenacyl group in the avobenzone structure. Steady-state photolysis of the dyad in hydrogen-donor solvents, monitored by UV-Vis spectrophotometry and HPLC, confirms the simultaneous photorelease of diclofenac and avobenzone. Laser flash photolysis and phosphorescence emission experiments allow us to gain insight into the photoactive triplet excited-state properties of the dyad. Finally, it is shown that avobenzone provides partial photoprotection to diclofenac from photocyclization to carbazole derivatives. [ABSTRACT FROM AUTHOR]

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 microenvironment 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-5-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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]