STUDIES OF TRANSITION-STATE STRUCTURES IN PHOSPHORYL TRANSFER-REACTIONS OF PHOSPHODIESTERS OF P-NITROPHENOL
STUDIES OF TRANSITION-STATE STRUCTURES IN PHOSPHORYL TRANSFER-REACTIONS OF PHOSPHODIESTERS OF P-NITROPHENOL
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DOI：
10.1021/ja00127a003
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发表时间：
1995-06-07
影响因子：
15
通讯作者：
CLELAND, WW
中科院分区：
文献类型：
--
作者：
HENGGE, AC;TOBIN, AE;CLELAND, WW
用重原子动力学同位素效应研究了磷酸二酯对叔丁基苯基对硝基苯磷酸酯（1）和3，3-二甲基丁基对硝基苯磷酸酯（2）的磷酰基转移反应的过渡态。研究了各种底物的碱性和酸性水解反应以及与蛇毒磷酸二酯酶I的反应。此外，还研究了双咪唑基β-环糊精和单咪唑基β-环糊精催化1的水解反应。测量的同位素效应是主要的O-18同位素效应在对硝基苯基离去基团，次要的O-18同位素效应在非桥氧原子，和N-15同位素效应在离去基团。这些数据表明，这两种化合物的水溶液水解反应具有类似的早期过渡态结构，几乎没有键断裂到离去基团。相反，在与磷酸二酯酶I的反应中，底物之间的过渡态结构存在显着差异。化合物1是咪唑基-β-环糊精催化剂的底物，其作为该底物的简单的通用碱催化剂起作用。在这些反应中，过渡态键断裂为离去基团比在未催化的水性反应中要先进得多。
Heavy-atom kinetic isotope effects have been used to study the transition states for a number of phosphoryl transfer reactions of the phosphodiesters p-tert-butylphenyl p-nitrophenyl phosphate (1) and 3,3-dimethylbutyl p-nitrophenyl phosphate (2). The alkaline and acid hydrolysis reactions and the reaction with phosphodiesterase I from snake venom were studied with each substrate. In addition, the hydrolysis reactions of 1 catalyzed by bis-(imidazolyl)- and by mono(imidazolyl)-beta-cyclodextrins were studied. The isotope effects measured were the primary O-18 isotope effect in the p-nitrophenyl leaving group, the secondary O-18 isotope effect in the nonbridge oxygen atoms, and the N-15 isotope effect in the leaving group. The data indicate similar early transition-state structures for the aqueous hydrolysis reactions of the two compounds with little bond cleavage to the leaving group. In contrast, significant differences in transition-state structure between the substrates are seen in their reactions with phosphodiesterase I. Compound 1 is a substrate for the imidazolyl-beta-cyclodextrin catalysts, which operate as simple general base catalysts for this substrate. Transition-state bond cleavage to the leaving group is much further advanced in these reactions than in the uncatalyzed aqueous reactions.