Single-Molecule Observation of the Intermediates in a Catalytic Cycle

• Published in: Journal of the American Chemical Society 2018-12, Vol.140 (50), p.17538-17546
• Main Authors: Ramsay, William J, Bell, Nicholas A. W, Qing, Yujia, Bayley, Hagan
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.8b09282

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.