Effect of Basic Amino Acids on Photoreaction of Ketoprofen in Phosphate Buffer Solution
Effect of Basic Amino Acids on Photoreaction of Ketoprofen in Phosphate Buffer Solution
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DOI：
10.1111/j.1751-1097.2012.01132.x
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发表时间：
2012-07
影响因子：
3.3
通讯作者：
Tadashi Suzuki;Yohei Osanai;T. Isozaki
中科院分区：
文献类型：
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作者：
Tadashi Suzuki;Yohei Osanai;T. Isozaki
采用瞬态吸收光谱法研究了酮洛芬（KP）在碱性氨基酸组氨酸（His）、赖氨酸（Lys）和精氨酸（Arg）存在下，在磷酸盐缓冲溶液（pH 7.4）中的光反应。用紫外光照射激发的去质子化形式的KP（KP−）通过脱羧反应产生负碳离子。结果发现，碳负离子从质子化氨基酸的侧链上夺取一个质子，产生3-乙基二苯甲酮酮基双自由基（EBPH）;然而，没有观察到与丙氨酸的反应。通过与His的质子转移反应，EBPH的相对产率约为100%。比其他两种碱性氨基酸大40倍，这表明His（质子化His）的质子供体能力应该相当高。研究NSAIDs与碱性氨基酸的光反应机理，对于了解NSAIDs在体内引起皮肤光敏化的初级反应是十分必要的。
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.