Ramsay William J, Bell Nicholas A W, Qing Yujia, Bayley Hagan
University of Oxford , Chemistry Research Laboratory , Oxford , OX1 3TA , United Kingdom.
J Am Chem Soc. 2018 Dec 19;140(50):17538-17546. doi: 10.1021/jacs.8b09282. Epub 2018 Dec 10.
The development of catalysts benefits from knowledge of the intermediate steps that accelerate the transformations of substrates into products. However, key transient species are often hidden in ensemble measurements. Here, we show that a protein nanoreactor can sample the intermediate steps in a catalytic cycle by the continuous single-molecule observation of a stoichiometric reaction in solution. By monitoring changes in the flow of ionic current through an α-hemolysin protein pore, we observed three intermediate metal-ligand complexes in a gold(I)-catalyzed reaction that converts an acetylenic acid to an enol lactone, revealing a transitional coordination complex that had been previously unobserved. A kinetic isotope effect helped assign the various metal-ligand species. Measurements of the lifetimes of the intermediates allowed a full kinetic analysis of the metal-catalyzed reaction cycle.
催化剂的发展受益于对加速底物转化为产物的中间步骤的了解。然而，关键的瞬态物种在整体测量中往往难以被发现。在此，我们展示了一种蛋白质纳米反应器能够通过对溶液中化学计量反应的连续单分子观测来获取催化循环中的中间步骤。通过监测穿过α-溶血素蛋白孔的离子电流的变化，我们在金（I）催化的将炔酸转化为烯醇内酯的反应中观察到了三种中间金属-配体配合物，揭示了一种此前未被观测到的过渡配位配合物。动力学同位素效应有助于确定各种金属-配体物种。对中间体寿命的测量使得能够对金属催化的反应循环进行完整的动力学分析。
