Tuning Mechanism through Buffer Dependence of Hydrogen Evolution Catalyzed by a Cobalt Mini-enzyme

Cobalt-mimochrome VI*a (CoMC6*a) is a synthetic mini-protein that catalyzes aqueous proton reduction to hydrogen (H₂). In buffered water, there are multiple possible proton donors, complicating the elucidation of the mechanism. We have found that the buffer pK_a and sterics have significant effects on activity, evaluated via cyclic voltammetry (CV). Protonated buffer is proposed to act as the primary proton donor to the catalyst, specifically through the protonated amine of the buffers that were tested. At a constant pH of 6.5, catalytic H₂ evolution in the presence of buffer acids with pK_a values ranging from 5.8 to 11.6 was investigated, giving rise to a potential–pK_a relationship that can be divided into two regions. For acids with pK_a values of ≤8.7, the half-wave catalytic potential (E_h) changes as a function of pK_a with a slope of −128 mV/pK_a unit, and for acids with pK_a of ≥8.7, E_h changes as a function of pK_a with a slope of −39 mV/pK_a unit. In addition, a series of buffer acids were synthesized to explore the influence of steric bulk around the acidic proton on catalysis. The catalytic current in CV shows a significant decrease in the presence of the sterically hindered buffer acids compared to those of their parent compounds, also consistent with the added buffer acid acting as the primary proton donor to the catalyst and showing that acid structure in addition to pK_a impacts activity. These results demonstrate that buffer acidity and structure are important considerations when optimizing and evaluating systems for proton-dependent catalysis in water.