Hydrogenase enzymes use first-row transition metals to interconvert H2 with protons and electrons, reactions that are important for the storage and recovery of energy from intermittent sources such as solar, hydroelectric, and wind. Here we present Ni(P(Cy)2N(Gly)2)2, a water-soluble molecular electrocatalyst with the amino acid glycine built into the diphosphine ligand framework. Proton transfer between the outer coordination sphere carboxylates and the second coordination sphere pendant amines is rapid, as observed by cyclic voltammetry and FTIR spectroscopy, indicating that the carboxylate groups may participate in proton transfer during catalysis. This complex oxidizes H2 (1-33 s(-1)) at low overpotentials (150-365 mV) over a range of pH values (0.1-9.0) and produces H2 under identical solution conditions (>2400 s(-1) at pH 0.5). Enzymes employ proton channels for the controlled movement of protons over long distances-the results presented here demonstrate the effects of a simple two-component proton channel in a synthetic molecular electrocatalyst.

Hydrogenases interconvert H 2 and protons at high rates and with high energy efficiencies, providing inspiration for the development of molecular catalysts. Studies designed to determine how the protein scaffold can influence a catalytically active site have led to the synthesis of amino acid derivatives of [Ni(P 2+ (CyAA). It is shown that theseCyAA derivatives can catalyze fully reversible H 2 production/ oxidation at rates approaching those of hydrogenase enzymes. The reversibility is achieved in acidic aqueous solutions (pH = 0-6), 1 atm 25% H 2 /Ar, and elevated temperatures (tested from 298 to 348 K) for the glycine (CyGly), arginine (CyArg), and arginine methyl ester (CyArgOMe) derivatives. As expected for a reversible process, the catalytic activity is dependent upon H 2 and proton concentrations. CyArg is significantly faster in both directions (∼300 s −1 H 2 production and 20 s −1 H 2 oxidation; pH = 1, 348 K, 1 atm 25% H 2 /Ar) than the other two derivatives. The slower turnover frequencies for CyArgOMe (35 s −1 production and 7 s −1 oxidation under the same conditions) compared with CyArg suggests an important role for the COOH group during catalysis. That CyArg is faster than CyGly (3 s −1 production and 4 s −1 oxidation) suggests that the additional structural features imparted by the guanidinium groups facilitate fast and reversible H 2 addition/release. These observations demonstrate that outer coordination sphere amino acids work in synergy with the active site and can play an important role for synthetic molecular electrocatalysts, as has been observed for the protein scaffold of redox active enzymes.hydrogenase mimics | reversible catalysis | amino acid catalysts | outer coordination sphere | homogeneous electrocatalysis H ydrogenases are metalloenzymes that interconvert H 2 and protons (Eq. 1), reactions necessary for biological processes within certain organisms to provide energy by splitting hydrogen, as well as to balance the redox potential in the cell (1-4). Their reversible catalytic behavior is a demonstration of their energy efficiency, indicating that they are operating at the equilibrium potential of the H 2 /H + couple. They are also very active under conditions optimized for a particular direction, operating at up to 20,000 s −1 for H 2 production (5) and 10,000 s −1 for H 2 oxidation (6). Under conditions where reversibility is optimized (3, 7-10), net turnover frequencies (TOFs) are typically slower. For hydrogenases attached to electrode surfaces, the TOFs are not always quantitated due to uncertainty in surface coverage (9), but in one example, TOFs for a series of mutants of Desulfovibrio fructosovorans [NiFe]-hydrogenase were reported, ranging from 3 to 500 s −1 for H 2 production and 600 to 1,000 s −1 for H 2 oxidation under one set of conditions (8).The ability of hydrogenases to function reversibly requiring no applied overpotential and with high catalytic TOFs is a direct reflection of their biological optimization, and a hallmark of enzymes. Reversibility requires enzym...

Redox active metalloenzymes play a major role in energy transformation reactions in biological systems. Examples include formate dehydrogenases, nitrogenases, CO dehydrogenase, and hydrogenases. Many of these reactions are also of interest to humans as potential energy storage or utilization reactions for photoelectrochemical, electrolytic, and fuel cell applications. These metalloenzymes consist of redox active metal centers where substrates are activated and undergo transformation to products accompanied by electron and proton transfer to or from the substrate. These active sites are typically buried deep within a protein matrix of the enzyme with channels for proton transport, electron transport, and substrate/product transport between the active site and the surface of the protein. In addition, there are amino acid residues that lie in close proximity to the active site that are thought to play important roles in regulating and enhancing enzyme activity. Directly studying the outer coordination sphere of enzymes can be challenging due to their complexity, and the use of modified molecular catalysts may allow us to provide some insight. There are two fundamentally different approaches to understand these important interactions. The "bottom-up" approach involves building an amino acid or peptide containing outer coordination sphere around a functional molecular catalyst, and the "top-down" approach involves attaching molecular catalyst to a structured protein. Both of these approaches have been undertaken for hydrogenase mimics and are the emphasis of this Account. Our focus has been to utilize amino acid or peptide based scaffolds on an active functional enzyme mimic for H2 oxidation and production, [Ni(P(R)2N(R('))2)2](2+). This "bottom-up" approach has allowed us to evaluate individual functional group and structural contributions to electrocatalysts for H2 oxidation and production. For instance, using amine, ether, and carboxylic acid functionalities in the outer coordination sphere enhances proton movement and results in lower catalytic overpotentials for H2 oxidation, while achieving water solubility in some cases. Amino acids with acidic and basic side chains concentrate substrate around catalysts for H2 production, resulting in up to 5-fold enhancements in rate. The addition of a structured peptide in an H2 production catalyst limited the structural freedom of the amino acids nearest the active site, while enhancing the overall rate. Enhanced stability to oxygen or extreme conditions such as strongly acidic or basic conditions has also resulted from an amino acid based outer coordination sphere. From the "top-down" approach, others have achieved water solubility and photocatalytic activity by associating this core complex with photosystem-I. Collectively, by use of this well understood core, the role of individual and combined features of the outer coordination sphere are starting to be understood at a mechanistic level. Common mechanisms have yet to be defined to predictably control these processes, bu...

Hydrogenase enzymes use Ni and Fe to oxidize H2 at high turnover frequencies (TOF) (up to 10,000 s(-1)) and low overpotentials (<100 mV). In comparison, the fastest reported synthetic electrocatalyst, [Ni(II)(P(Cy)2N(tBu)2)2](2+), oxidizes H2 at 60 s(-1) in MeCN under 1 atm H2 with an unoptimized overpotential of ca. 500 mV using triethylamine as a base. Here we show that a structured outer coordination sphere in a Ni electrocatalyst enhances H2 oxidation activity: [Ni(II)(P(Cy)2N(Arg)2)2](8+) (Arg=arginine) has a TOF of 210 s(-1) in water with high energy efficiency (180 mV overpotential) under 1 atm H2 , and 144,000 s(-1) (460 mV overpotential) under 133 atm H2. The complex is active from pH 0-14 and is faster at low pH, the most relevant condition for fuel cells. The arginine substituents increase TOF and may engage in an intramolecular guanidinium interaction that assists in H2 activation, while the COOH groups facilitate rapid proton movement. These results emphasize the critical role of features beyond the active site in achieving fast, efficient catalysis.