Photoreaction dynamics of 2-(3-benzoylphenyl)propionic acid (ketoprofen, KP), one of nonsteroidal anti-inflammatory drugs, with histidine in a phosphate buffer solution (pH 7.4) was investigated with the laser flash photolysis. The deprotonated form of KP (KP(-)) was decarboxylated via UV laser excitation to form a carbanion. It was found that histidine accelerates the protonation reaction of the carbanion to 3-ethylbenzophenone ketyl biradical (3-EBPH) for the first time. The experimental results of the photoreaction of KP with alanine as well as the photoreaction of KP with 4-methylimidazole (a part of the side chain of histidine) in methanol, clearly showed that the protonated form of histidine is a key species for the protonation reaction of the carbanion. These series of the initial reactions should result in the occurrence of photosensitization in vivo. The reaction mechanism was discussed in detail.

Photoreaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen, KP) with basic amino acids (histidine, lysine, and arginine) and dipeptides (carnosine and anserine) including a histidine moiety in phosphate buffer solution (pH 7.4) has been investigated with transient absorption spectroscopy. With UV irradiation KP(-) gave rise to a carbanion through a decarboxylation reaction, and the carbanion easily abstracted a proton from the surrounding molecule to yield a 3-ethylbenzophenone ketyl biradical (EBPH). The dipeptides as well as the basic amino acids were found to accelerate the proton transfer reaction whereas alanine and glycine had no effect on the reaction, revealing that these amino acids having a protonated side chain act as a proton donor. The formation quantum yield of EBPH was estimated to be fairly large by means of an actinometrical method with benzophenone, and the bimolecular reaction rate constant for the proton transfer between the carbanion and the protonated basic amino acids or the protonated dipeptides was successfully determined. It has become apparent that the bimolecular reaction rate constant for the proton transfer depended on the acid dissociation constant for the side chain of the amino acids for the first time. This reaction mechanism was interpreted by difference of the heat of reaction for each basic amino acid based on the thermodynamical consideration. These results strongly suggest that the side chain of the basic amino acid residue in protein should play an important role for photochemistry of KP in vivo.

Photoreaction of ketoprofen (KP), one of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs), was studied with transient absorption spectroscopy in phosphate buffer solution (pH 7.4) in the presence of basic amino acids of histidine (His), lysine (Lys) and arginine (Arg). Deprotonated form of KP (KP(-)) excited with UV-light irradiation gave rise to carbanion through a decarboxylation reaction. It was found that carbanion abstracted a proton from the side chain of the protonated amino acids to yield 3-ethylbenzophenone ketyl biradical (EBPH); however, no reaction was observed with alanine. The relative yield of EBPH by the proton transfer reaction with His was ca. 40 times larger than that of the other two basic amino acids, suggesting that the proton-donating ability of His (protonated His) should be quite high. The information on the photoreaction mechanism of NSAIDs with basic amino acids was essential to understand primary reaction of excited NSAIDs in vivo causing photosensitization on human skin.

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