Direct Observation of a Cross-Coupling Catalyst Intermediate via Single-Molecule Spectroscopy

Abstract Single-molecule measurements on molecular catalysts are uniquely poised to allow observation of unsynchronized chemical dynamics and transient intermediates that are not observable using traditional bulk techniques. However, single-molecule fluorescence spectroscopy is typically performed at nanomolar concentrations, far lower than typical synthetic conditions. Here, we use nanophotonic zero-mode waveguides (ZMWs) to enable observation of the dynamics of a single catalyst under synthetically relevant (micromolar) reaction concentrations. We deploy ZMWs to perform the direct observation of a previously hypothesized intermediate of Pd-PEPPSI (Pyridine-Enhanced Precatalyst Preparation, Stabilization, and Initiation), a well-known molecular C–C cross-coupling catalyst, by using a fluorescently labeled ligand to report on ligand binding and dissociation. Kinetic analysis of single-catalyst ligand dynamics reveals how the presence of cross-coupling reactants influences the underlying mechanism. This paradigm for single-molecule investigation of molecular catalysts at synthetically relevant concentrations is general for investigation of a wide variety of ligand and reactant dynamics.