| Abstract
| - The aim of the present work was to find a ketoprofen (KP) equivalent suitable for time-resolved studies onthe interactions of its KP-like triplet state with biomolecules or their simple building blocks, underphysiologically relevant conditions. Such a compound should fulfill the following requirements: (i) it shouldbe soluble in aqueous media; (ii) its triplet lifetime should be longer than that of KP, ideally in the microsecondrange; and (iii) its photodecarboxylation should be slow enough to avoid interference in the time-resolvedstudies associated with formation of photoproducts. Here, the glycine derivative of ketoprofen (KPGly) hasbeen found to fulfill all the above requirements. In a first stage, the attention has been focused on thephotophysical and photochemical properties of KPGly, and then on its excited-state interactions with keyamino acids and nucleosides. In acetonitrile, the typical benzophenone-like triplet−triplet absorption (3KPGly)with λmax at 520 nm and a lifetime of 5.3 μs was observed. This value is very close to that of 3KP (5.6 μs)obtained under the same conditions. In methanol, the 3KPGly features were also close to those of 3KP withdetection of a short-lived triplet state that evolves to give a ketyl radical. By contrast with the behavior ofKP, in deaerated aqueous solutions at pH = 7.4, the transient detected in the case of KPGly displayed twobands at λmax at 330 and 520 nm, very similar to those observed in acetonitrile solution but with a lifetimeof 7.5 μs at 520 nm. Hence, it was assigned to the KPGly triplet. In the case of KP, efficient decarboxylationoccurs in the subnanosecond time scale, via intramolecular electron transfer. This process gives rise to adetectable carbanion intermediate (lifetime ∼250 ns) and prevents detection of the shorter-lived 3KP signal.In a second stage, the attention has been focused on the excited-state interactions between 3KPGly and aminoacids or nucleosides; for this purpose, 2‘-deoxyguanosine (dGuo), thymidine (Thd), tryptophan (Trp), andtyrosine (Tyr) have been chosen as photosensitization targets. In general, efficient quenching (rate constantkq> 109 M-1 × s-1) was observed; it was attributed for dGuo, Tyr, and Trp to a photochemical reactioninvolving initial electron transfer from the biological target to 3KPGly, followed by proton transfer from theamino acid or the nucleoside radical cation to KPGly-•. As a matter of fact, ketyl radical together withguanosinyl, tyrosinyl, or tryptophanyl radicals were detected; this supports the proposed mechanism. Theresults with Thd were somewhat different, as the efficient 3KPGly quenching was ascribed to oxetane formationby a Paterno Büchi photocycloaddition.
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