Exploring the Dynamics of Suzuki–Miyaura Cross-Coupling Reactions via Single-Molecule Fluorescence Microscopy: Catalytic Efficiency from SM-TOF Measurements

In this study, four Suzuki–Miyaura cross-coupling reactions utilizing palladium as a catalyst at the single-molecule (SM) level are investigated, employing total internal reflection fluorescence microscopy and super-resolved optical imaging. Three dispersion methodologies of the precatalyst Pd(II) are examined. The first one involves direct adsorption of Pd onto ionic sites SiO2– of the glass surface. In the second, Pd is complexed with a ligand bound to the silica surface, and in the third, Pd complexation occurs with a ligand bound to the surface of a microzeolite particle used as a reaction template. All three methods use extremely low catalyst densities. Analysis of fluorescence intermittency from localized nanospots yields the catalyst conversion rate or single-molecule turnover frequency (SM-TOF), allowing calculation of the average number of product molecules generated by a single catalytic center over time. A significant enhancement in catalytic efficiency is found in the microzeolite template when compared with Pd adsorbed on a ligand-free silica glass surface. In the microzeolite template, each catalyst center on average forms 95 molecules per minute, while Pd adsorbed on silica glass produces only 29 molecules per minute, both with weak dependency among the four reactions studied. Stochastic simulation of the cross-coupling reaction cycle indicates that the SM-TOF value is proportional to the product of the rate constant of the determining step of the cycle by the probability of the catalyst being in its active Pd(0) state. Under this approximation, the rate constant of the determining step of the Suzuki–Miyaura cross-coupling reaction cycle is calculated for all four reactions studied.