Semiempirical method for examining asynchronicity in metal-oxido-mediated C-H bond activation
Semiempirical method for examining asynchronicity in metal-oxido-mediated C-H bond activation
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DOI：
10.1073/pnas.2108648118
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发表时间：
2021-09-07
影响因子：
11.1
通讯作者：
Borovik, A. S.
中科院分区：
文献类型：
--
作者：
Barman, Suman K.;Yang, Meng-Yin;Borovik, A. S.
通过热力学上强的 C-H 键的裂解进行底物的氧化是哺乳动物新陈代谢的重要组成部分。这些反应主要由产生高价金属氧化物的酶进行，这些酶直接负责裂解 C-H 键。虽然人们对这些瞬时中间体的身份了解很多，但使金属氧化物物质完成如此困难的反应的机制因素仍然不完整。对于合成金属氧化物物质，C-H 键断裂通常在机械上被描述为同步质子耦合电子转移 (PCET)。然而，已经出现的数据表明，M-氧化单元的碱性是实现酶功能的关键决定因素，因此需要替代机制，使质子转移（PT）比电子转移（ET）具有更主导的作用。为了弥补这一知识差距，研究了单体 MnIV-氧化络合物与一系列外部底物的反应性，导致其二阶速率常数随 C-H 键的酸度变化超过 104。包括同步 PCET 或限速 PT 以及随后的 ET 的机制并不能解释我们的结果，这导致提出了一种具有以 PT 为主的异步过渡状态的 PCET 机制。为了支持这一前提，我们报告了一种半经验自由能分析，该分析可以预测 PT 和 ET 对于一组给定底物的相对贡献。这些发现强调了为什么在 C-H 官能化中需要考虑 M-氧化单元的碱性。
The oxidation of substrates via the cleavage of thermodynamically strong C-H bonds is an essential part of mammalian metabolism. These reactions are predominantly carried out by enzymes that produce high-valent metal-oxido species, which are directly responsible for cleaving the C-H bonds. While much is known about the identity of these transient intermediates, the mechanistic factors that enable metal-oxido species to accomplish such difficult reactions are still incomplete. For synthetic metal-oxido species, C-H bond cleavage is often mechanistically described as synchronous, proton-coupled electron transfer (PCET). However, data have emerged that suggest that the basicity of the M-oxido unit is the key determinant in achieving enzymatic function, thus requiring alternative mechanisms whereby proton transfer (PT) has a more dominant role than electron transfer (ET). To bridge this knowledge gap, the reactivity of a monomeric MnIV-oxido complex with a series of external substrates was studied, resulting in a spread of over 104 in their second-order rate constants that tracked with the acidity of the C-H bonds. Mechanisms that included either synchronous PCET or rate-limiting PT, followed by ET, did not explain our results, which led to a proposed PCET mechanism with asynchronous transition states that are dominated by PT. To support this premise, we report a semiempirical free energy analysis that can predict the relative contributions of PT and ET for a given set of substrates. These findings underscore why the basicity of M-oxido units needs to be considered in C-H functionalization.