13C Kinetic Isotope Effects and the Mechanism of the Uncatalyzed Decarboxylation of Orotic Acid
13C Kinetic Isotope Effects and the Mechanism of the Uncatalyzed Decarboxylation of Orotic Acid
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13C动力学同位素效应及乳清酸非催化脱羧机理
DOI：
10.1021/ja993392m
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发表时间：
2000
影响因子：
15
通讯作者：
Jeehiun K. Lee
中科院分区：
文献类型：
--
作者：
D. A. Singleton;S. R. Merrigan;B. Kim;P. Beak;A. M. Phillips;Jeehiun K. Lee
一套完整的1, 3C动力学同位素效应的热脱羧的1，3-二甲基乳清酸和理论预测的同位素效应通过O-2或O-4质子化途径脱羧进行了比较。实验和计算的同位素效应的最佳对应被发现为O-4质子化的机制。这一观察结果和计算的反应势垒支持先前预测的这种途径的偏好。的O-4质子化机制的偏好被发现，从一般偏好O-4质子化的O-2质子化的乳清酸/尿嘧啶系列，并没有显着的额外的稳定性出现与形成一个正式的卡宾在O-4质子化脱羧。非催化反应的羧酸盐同位素效应远小于最近报道的酶催化的同位素效应，表明非催化和酶催化机制之间存在一些分歧。
A complete set of 13C kinetic isotope effects were determined for the thermal decarboxylation of 1,3-dimethylorotic acid and compared with theoretically predicted isotope effects for decarboxylation via either O-2 or O-4 protonated pathways. The best correspondence of experimental and calculated isotope effects is found for the O-4 protonated mechanism. This observation and the calculated reaction barriers support the previously predicted preference for this pathway. The preference for the O-4 protonated mechanism is found to result from a general predilection for O-4 protonation over O-2 protonation in the orotate/uracil series, and no significant extra stability appears associated with the formation of a formal carbene in the O-4 protonated decarboxylation. The carboxylate isotope effect for the uncatalyzed reaction is much smaller than the enzyme-catalyzed isotope effect recently reported, suggesting some divergence between uncatalyzed and enzyme-catalyzed mechanisms.