TRANSITION-STATE STRUCTURAL VARIATION IN A MODEL FOR CARBONYL REDUCTION BY LACTATE-DEHYDROGENASE - COMPUTATIONAL VALIDATION OF EMPIRICAL PREDICTIONS BASED UPON ALBERY-MORE OFERRALL-JENCKS DIAGRAMS
TRANSITION-STATE STRUCTURAL VARIATION IN A MODEL FOR CARBONYL REDUCTION BY LACTATE-DEHYDROGENASE - COMPUTATIONAL VALIDATION OF EMPIRICAL PREDICTIONS BASED UPON ALBERY-MORE OFERRALL-JENCKS DIAGRAMS
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DOI：
10.1021/ja00039a064
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发表时间：
1992-06-17
影响因子：
15
通讯作者：
WILLIAMS, IH
中科院分区：
文献类型：
--
作者：
WILKIE, J;WILLIAMS, IH
采用AM 1半经验分子轨道方法，对二氢吡啶（氢化物供体）和咪唑鎓（质子供体）还原甲醛的过渡态结构进行了定位和表征。这种协同反应的质子转移（HT）和质子转移（PT）组件是动力学耦合，但动态解耦。增加的咪唑部分的碱性，通过适当放置的偶极的可变幅度的装置，导致在TS中的PT的程度基本上没有变化，但在HT的程度大幅增加。该计算结果验证了基于Albery-More O 'Ferrall-Jencks图的预测。相应地，初级动力学同位素效应（KIE）计算的氘核取代的转移质子显示出很小的变化，但有一个显着增加的幅度计算的初级KIE的转移磷酰胺由氘化物取代的TS结构的咪唑部分的碱度的变化。这与TS结构和初级KIE大小之间关系的传统观点一致。
The transition-state (TS) structure for reduction of formaldehyde by dihydropyridine (hydride donor) and imidazolium (proton donor) has been located and characterized by use of the AM1 semiempirical MO method. The hydride-transfer (HT) and proton-transfer (PT) components of this concerted reaction are kinetically coupled but dynamically uncoupled. Increasing the basicity of the imidazole moiety, by means of a suitably placed dipole of variable magnitude, leads to essentially no change in the degree of PT in the TS but to a substantial increase in the degree of HT. This computational result validates the prediction made on the basis of an Albery-More O'Ferrall-Jencks diagram. Correspondingly, the primary kinetic isotope effect (KIE) calculated for replacement of the transferring proton by a deuteron shows little change, but there is a significant increase in the magnitude of the calculated primary KIE for replacement of the transferring protide by a deuteride as the TS structure changes with increasing basicity of the imidazole moiety. This accords with the conventional view of the relationship between TS structure and the magnitude of primary KIEs.