Imbalanced Transition States from α-H/D and Remote β-Type N -CH/D Secondary Kinetic Isotope Effects on the NADH/NAD + Analogues in Their Hydride Tunneling Reactions in Solution
Imbalanced Transition States from α-H/D and Remote β-Type N -CH/D Secondary Kinetic Isotope Effects on the NADH/NAD + Analogues in Their Hydride Tunneling Reactions in Solution
复制标题
α-H/D 和远程 β-型 N -CH/D 二次动力学同位素对 NADH/NAD 类似物在溶液中氢化物隧道反应中的不平衡过渡态影响
DOI：
10.1021/acs.joc.9b00412
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Lu, Yun
中科院分区：
文献类型：
--
作者：
Ma, Li;Sakhaee, Nader;Jafari, Shabnam;Wilhelm, Samantha;Rahmani, Paniz;Lu, Yun
测定了10-甲基吖啶（MAH）、9,10-二甲基吖啶（DMAH）、1,3-二甲基-2-苯基苯并咪唑啉（DMPBIH）与几种氢化物受体/供体在乙腈中发生氢化物转移反应时α-H/D（如有）和远端β-型- ch3 /CD32°的动力学同位素效应（KIEs）。计算了相应的平衡同位素效应（EIEs）。利用文献资料建立了几个密切相关的氢化物转移反应的Hammett相关式。相对于基于KIE/EIE比较和Hammond假设的半经典预测，MAH和MA+上的α-2°KIEs都有所膨胀。这与先前发表的不寻常的1°和2°KIE行为一起强烈表明了h隧道机制。通过与eie的比较，用α-2°KIEs分析了反应中心C和- ch3 /CD32°KIEs的再杂化，计算了h隧穿过程中含N结构上的电荷分布。再杂交似乎滞后于供体部分的电荷发育。隧穿就绪过渡态的电荷分布符合Hammett相关；供体呈生成物状，受体呈反应物状，表明“飞行中的”原子核所携带的部分负电荷具有“水合”性质。结果与NADH/NAD+ α-2°KIEs及密切相关酶的Hammett相关性进行了比较。结果表明，这些酶能提高h隧穿的可能性。
The α-H/D (if available) and remote β-typeN-CH3/CD32° kinetic isotope effects (KIEs) on 10-methylacridine (MAH), 9,10-dimethylacridine (DMAH), 1,3-dimethyl-2-phenylbenzimidazoline (DMPBIH) and on the oxidized forms MA+and DMA+, in their hydride transfer reactions with several hydride acceptors/donors in acetonitrile, were determined. The corresponding equilibrium isotope effects (EIEs) were computed. Hammett correlations of several closely related hydride transfer reactions were constructed using the literature data. The α-2° KIEs on both MAH and MA+are inflated relative to the semiclassical prediction on the basis of the KIE/EIE comparison and Hammond’s postulate. This together with previously published unusual 1° and 2° KIE behaviors strongly suggest a H-tunneling mechanism. By comparing with the EIEs, the α-2° KIEs were used to analyze the rehybridization of the reaction center C and theN-CH3/CD32° KIEs to calculate the charge distribution on the structure containing N during H-tunneling. The rehybridization appears to lag behind the charge development in the donor moiety. The charge distribution at the tunneling ready transition state is in agreement with the Hammett correlations; the donor is product-like, and the acceptor is reactant-like, indicative of a partial negative charge borne by the “in-flight” nucleus being “hydridic” in character. Results were compared with the α-2° KIEs on NADH/NAD+and the Hammett correlations in closely related enzymes. The comparison implicates that the H-tunneling probability would be enhanced by these enzymes.