Direct Correlation between Donor–Acceptor Distance and Temperature Dependence of Kinetic Isotope Effects in Hydride-Tunneling Reactions of NADH/NAD + Analogues
Direct Correlation between Donor–Acceptor Distance and Temperature Dependence of Kinetic Isotope Effects in Hydride-Tunneling Reactions of NADH/NAD + Analogues
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NADH/NAD 类似物氢化物隧道反应中供体-受体距离与动力学同位素效应的温度依赖性之间的直接相关性
DOI：
10.1021/acs.joc.1c00497
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Lu, Yun
中科院分区：
文献类型：
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作者：
Bai, Mingxuan;Koirala, Shailendra;Lu, Yun
最近对酶和溶液中氢转移反应的初级动力学同位素效应（1° KIE）的结构效应的研究表明，更刚性的反应体系导致1° KIE的温度依赖性较弱，即，较小的同位素活化能差（ΔEa=EaD-EaH）。这已经在当代振动辅助激活H-隧穿（VA-AHT）模型中得到解释，其中刚性是根据重原子运动采样的隧穿就绪态（TRS）的施主-受主距离（DADTRS）密度定义的。为了测试模型中DADTRs和Δ Ea之间的关系，我们开发了一种计算方法来获得氢转移反应的TRS结构。该方法被应用于三个NADH/NAD+类似物的氢化物转移反应，其ΔEa以及二级（2°）KIE已被报道。根据每个TRS结构计算的2° KIE与观测值拟合，以获得最佳TRS/DADTRS。发现DADTRS越短，ΔEa越小。这似乎支持VA-AHT模型。此外，在弯曲的TRS结构的杂交分析表明，在供体-受体中心的再杂交比从经典机制预测的要先进得多。这意味着需要更多的轨道准备才能发生非经典H隧穿。
Recent study of structural effects on primary kinetic isotope effects (1° KIEs) of H-transfer reactions in enzymes and solution revealed that a more rigid reaction system gave rise to a weaker temperature dependence of 1° KIEs, i.e., a smaller isotopic activation energy difference (ΔEa=EaD–EaH). This has been explained within the contemporary vibrationally assisted activated H-tunneling (VA-AHT) model in which rigidity is defined according to the density of donor–acceptor distance (DADTRS) populations at the tunneling ready state (TRS) sampled by heavy atom motions. To test the relationship between DADTRSand ΔEain the model, we developed a computational method to obtain the TRS structures for H-transfer reactions. The method was applied to three hydride transfer reactions of NADH/NAD+analogues for which the ΔEa’s as well as secondary (2°) KIEs have been reported. The 2° KIEs computed from each TRS structure were fitted to the observed values to obtain the optimal TRSs/DADTRS’s. It was found that a shorter DADTRSdoes correspond with a smaller ΔEa. This appears to support the VA-AHT model. Moreover, an analysis of hybridizations at the bent TRS structures shows that rehybridizations at the donor–acceptor centers are much more advanced than predicted from the classical mechanism. This implies that more orbital preparations are required for the nonclassical H-tunneling to take place.