Photochemical and Photobiological Properties of Ketoprofen Associated With the Benzophenone Chromophore

Abstract

Irradiation of ketoprofen in neutral aqueous medium gave rise to 3-ethylbenzophenone as the major photoproduct. Its formation is justified via protonation of a benzylic carbanion or hydrogen abstraction by a benzylic radical. Minor amounts of eight additional compounds were isolated. Four of them are derived from the benzylic radical: 3-(1-hydroperoxyethyl)benzophenone, 3-(1-hydroxyethyl)benzophenone, 3-acetylbenzophenone and 2,3-bis-(3-benzoylphenyl)butane. The other four products involve initial hydrogen abstraction by the excited benzophenone chromophore of ketoprofen: 1,2-bis-(3-ethylphenyl)-1,2-diphenyl-1,2-ethanediol, 2-(3-benzoylphenyl)-1-(3-ethylphenyl)-1-phenylpropan-1-ol, alpha-(3-ethylphenyl)phenylmethanol, 1,2-bis-[3-(2-hydroxycarbonylethyl) phenyl]-1,2-diphenyl-1,2-ethanediol. The latter process was found to mediate the photoperoxidation of linoleic acid through a type I mechanism, as evidenced by the inhibition produced by the radical scavengers butylated hydroxyanisole and reduced glutathione. The major photoproduct, which contains the benzophenone moiety but lacks the propionic acid side chain, also photosensitized linoleic acid peroxidation. Because lipid peroxidation is indicative of cell membrane lysis, the above findings are highly relevant to explain the photobiological properties of ketoprofen.

Photodecarboxylation of N-Adamantyl- and N-Phenylphthalimide Dipeptide Derivatives

“…5 The other suggested mechanism includes photoejection of an electron from the carboxylates and formation of radicals. 6 A special interest was directed to the photodecarboxylation of ketoprofene and similar derivatives. 7 Although some controversy was encountered regarding the reactive excited state of ketoprofen, 8 it is generally accepted that the decarboxylation gives carbanionic species.…”

“…All NMR spectra were measured in CDCl 3, DMSO-d 6 or CD 3 OD using tetramethylsilane as a reference. Highresolution mass spectra (HRMS) were measured on an Applied Biosystems 4800 Plus MALDI TOF/TOF instrument.…”

Study of Compounds Suppressing Free Radical Generation from UV-Exposed Ketoprofen

“…Although the free radical species were speculated to be benzophenone, [9][10][11][12] benzoyl radical, 13) carbonyl radical 14) and superoxide anion, 15) their true identities remain unknown to this day. We elucidated the pathways for the photo-degradation of ketoprofen and the generation of free radicals in our previous study.…”

Interaction of the Electrophilic Ketoprofenyl-Glucuronide and Ketoprofenyl-Coenzyme A Conjugates with Cytosolic GlutathioneS-Transferases

“…Therefore, another approach was undertaken, using KPF-SCoA as a photoaffinity probe combined with ligand protection experiments. It was indeed reported previously that KPF can bind to proteins upon UV irradiation through the benzophenone moiety (Boscá et al, 1994;Chuang et al, 1999). We observed in preliminary experiments that KPF could photolabel GST (E. Battaglia and D. Bagrel, unpublished observations).…”