Suzuki Tadashi, Okita Takeshi, Osanai Yohei, Ichimura Teijiro
Department of Chemistry and Materials Science, Tokyo Institute of Technology, Tokyo, Japan.
J Phys Chem B. 2008 Nov 27;112(47):15212-6. doi: 10.1021/jp8063382.
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.
采用激光闪光光解技术研究了非甾体抗炎药之一的2-(3-苯甲酰基苯基)丙酸（酮洛芬，KP）与组氨酸在磷酸盐缓冲溶液（pH 7.4）中的光反应动力学。通过紫外激光激发，KP的去质子化形式（KP(-)）发生脱羧反应形成碳负离子。首次发现组氨酸加速了碳负离子质子化生成3-乙基二苯甲酮酮基双自由基（3-EBPH）的反应。KP与丙氨酸的光反应以及KP与4-甲基咪唑（组氨酸侧链的一部分）在甲醇中的光反应实验结果清楚地表明，组氨酸的质子化形式是碳负离子质子化反应的关键物种。这一系列初始反应应会导致体内发生光敏化。详细讨论了反应机理。
