Khade Rahul L, Chandgude Ajay L, Fasan Rudi, Zhang Yong
Department of Chemistry and Chemical Biology, Stevens Institute of Technology, 1 Castle Point on Hudson, Hoboken, NJ 07030 (USA).
Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY 14627 (USA).
ChemCatChem. 2019 Jul 4;11(13):3101-3108. doi: 10.1002/cctc.201801755. Epub 2019 May 8.
Recent studies reported the development of biocatalytic heme carbenoid Si-H insertions for the selective formation of carbon-silicon bonds, but many mechanistic questions remain unaddressed. To this end, a DFT mechanistic investigation was performed which reveals an Fe-based concerted hydride transfer mechanism with early transition state feature. The results from these computational analyses are consistent with experimental data of radical trapping, kinetic isotope effects, and structure-reactivity data using engineered variants of hemoproteins. Detailed geometric and electronic profiles along the heme catalyzed Si-H insertion pathways were provided to help understand the origin of experimental reactivity trends. Quantitative relationships between reaction barriers and some properties such as charge transfer from substrate to heme carbene and Si-H bond length change from reactant to transition state were found. Results suggest catalyst modifications to facilitate the charge transfer from the silane substrate to the carbene, which was determined to be a major electronic driving force of this reaction, should enable the development of improved biocatalysts for Si-H carbene insertion reactions.
最近的研究报道了用于选择性形成碳-硅键的生物催化血红素类卡宾硅氢插入反应的进展，但许多机理问题仍未得到解决。为此，进行了一项密度泛函理论（DFT）机理研究，揭示了一种具有早期过渡态特征的基于铁的协同氢化物转移机制。这些计算分析的结果与使用血红蛋白工程变体的自由基捕获、动力学同位素效应和结构-反应性数据的实验数据一致。提供了沿血红素催化的硅氢插入途径的详细几何和电子概况，以帮助理解实验反应性趋势的起源。发现了反应势垒与一些性质之间的定量关系，如从底物到血红素卡宾的电荷转移以及从反应物到过渡态的硅氢键长度变化。结果表明，对催化剂进行修饰以促进硅烷底物向卡宾的电荷转移（这被确定为该反应的主要电子驱动力），应该能够开发出用于硅氢卡宾插入反应的改进型生物催化剂。
