Mechanism of Photoinduced Decomposition of Ketoprofen

Abstract

UV-induced decarboxylation of the NSAID ketoprofen, followed by activation of molecular oxygen or formation of a decarboxylated peroxide adduct, is explored using computational quantum chemistry. The excited energy surfaces reveal that the neutral species will not decarboxylate, whereas the deprotonated acid decarboxylates spontaneously in the triplet state, and with an associated 3?5 kcal/mol barrier from several low-lying excited singlet states. The observed long lifetimes of the decarboxylated anion is explained in terms of the high stability of the triplet benzoyl ethyl species with protonated carbonylic oxygen, from which there is no obvious decay channel. Mechanisms for the generation of singlet oxygen and superoxide are discussed in detail. Addition of molecular oxygen to give the corresponding peroxyl radical capable of initiating propagating lipid peroxidation reactions is also explored. The computed data explains all features of the observed experimental observations made to date on the photodegradation of ketoprofen.