Photooxygenation mechanisms in naproxen-amino acid linked systems

摘要

The photooxygenation of model compounds containing the two enantiomers of naproxen (NPX) co-valently linked to histidine (His), tryptophan (Trp) and tyrosine (Tyr) has been investigated by steady state irradiation, fluorescence spectroscopy and laser flash photolysis. The NPX-His systems presented the highest oxygen-mediated photoreactivity. Their fluorescence spectra matched that of isolated NPX and showed a clear quenching by oxygen, leading to a diminished production of the NPX triplet excited state (~3NPX*-His). Analysis of the NPX-His and NPX-Trp photolysates by UPLC-MS-MS revealed in both cases the formation of two photoproducts, arising from the reaction of singlet oxygen ~1O2 with the amino acid moiety. The most remarkable feature of NPX-Trp systems was a fast and stereoselective intramolecular fluorescence quenching, which prevented the efficient formation of ~3NPX*-Trp, thus explaining their lower reactivity towards photooxygenation. Finally, the NPX-Tyr systems were nearly unreactive and exhibited photophysical properties essentially coincident with those of the parent NPX. Overall, these results point to a type II photooxygenation mechanism, triggered by generation of ~1O2 from the ~3NPX* chromophore.