STRUCTURE-REACTIVITY CORRELATION FOR HYDROLYSIS OF PHOSPHORAMIDATE MONOANIONS
STRUCTURE-REACTIVITY CORRELATION FOR HYDROLYSIS OF PHOSPHORAMIDATE MONOANIONS
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DOI：
10.1021/ja00745a032
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发表时间：
1971-01-01
影响因子：
15
通讯作者：
SAMPSON, EJ
中科院分区：
文献类型：
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作者：
BENKOVIC, SJ;SAMPSON, EJ
磷酸-磷酰胺单阴离子的水解速率常数与离去胺的浓度之间的结构-反应性关系是非线性的。数据中的拐点发生在pKh»8，归因于非稳态两性离子浓度的变化，该变化与母体胺的浓度成正比。对于第二解离常数大于7.2的磷酰胺类化合物，水溶液中的平衡倾向于两性离子。在这些数据的基础上，对亲核攻击磷酸酯的过渡态进行了半定量描述，其特征是对离开基团的键切割远远超过对进入的亲核试剂的键形成。这一发现与o-和s -磷酸单酯和二酯的数据相结合，表明五价中间体可能不会出现在无环单酯和二酯水解的反应途径上。在酶催化的己糖和三磷酸腺苷磷酸化过程中，各种磷酸酯作为底物或中间体的参与已得到充分证实。3-6以下是两个例子。磷酸腺苷二磷酸磷酸转移酶利用tv -磷酸甘氨酸、n -磷酸组氨酸或磷酸酰胺作为来源促进二磷酸腺苷和三磷酸的相互转化。葡萄糖6-磷酸酶通过酶A ' -磷酸化组氨酸中间体催化[p32 -]从葡萄糖6-磷酸到水或无机磷酸盐的转移。[56]一些定量研究涉及了磷酰胺和各种iv -酰基和iv -芳基衍生物的非酶水解。7-9此外，已证明磷酸酰胺单阴离子7 89-10和a
The structure-reactivity relationship which correlates the rate constants for the hydrolysis of phos-phoramidate monoanions with the pifa of the leaving amine is nonlinear. The inflectionpoint in the data which occurs at pKh» 8 is attributed to changes in the nonsteady-state zwitterion concentration which are directly proportional to the pof the parent amine. The equilibrium favorsthe zwitterionic species in aqueous solution for those phosphoramidates whose second dissociation constant is greater than 7.2. On the basis of these data, a semiquantitative description of the transition state for nucleophilic attack on phosphoramidates is developed which features bond cleavageto the departing group as greatly exceeding bond formation to the incoming nucleophile. This finding in conjunction with data for O-and S-phosphate mono- and diesters suggests that pentacovalent intermediates probably do not occur on the reaction pathways for acyclic mono- and diester hydrolysis. he involvement of various phosphoramidates either as substrates or intermediates in the enzyme-catalyzed phosphorylation of hexose and adenosine tri-phosphate is well established. 3-6 Two examples follow. Phosphoramidate-adenosine diphosphate phospho-transferase facilitates the interconversion of adenosine di-and triphosphate utilizing TV-phosphorylglycine, N-phosphorylhistidine, or phosphoramidate as the [P032-] source. 3 Glucose 6-phosphatase catalyzes the transfer of [P0 32-] from glucose 6-phosphate to water or inor-ganic phosphatethrough an enzymic A’-phosphorylhistidine intermediate. 4 56Several quantitative studies have dealt with the nonenzymic hydrolysis of phos-phoramidate and various iV-acyl and iV-aryl deriva-tives. 7-9 In addition it has been demonstrated that the hydrolysis of phosphoramidate monoanion7 89-10 and a