Hydrogenase enzymes efficiently process H2 and protons at organometallic FeFe, NiFe, or Fe active sites. Synthetic modeling of the many H2ase states has provided insight into H2ase structure and mechanism, as well as afforded catalysts for the H2 energy vector. Particularly important are hydride-bearing states, with synthetic hydride analogues now known for each hydrogenase class. These hydrides are typically prepared by protonation of low-valent cores. Examples of FeFe and NiFe hydrides derived from H2 have also been prepared. Such chemistry is more developed than mimicry of the redox-inactive monoFe enzyme, although functional models of the latter are now emerging. Advances in physical and theoretical characterization of H2ase enzymes and synthetic models have proven key to the study of hydrides in particular, and will guide modeling efforts toward more robust and active species optimized for practical applications.

Quinones participate in diverse electron transfer and proton-coupled electron transfer processes in chemistry and biology. To understand the relationship between these redox processes, an experimental study was carried out to probe the 1 e– and 2 e–/2 H+ reduction potentials of a number of common quinones. The results reveal a non-linear correlation between the 1 e– and 2 e–/2 H+ reduction potentials. This unexpected observation prompted a computational study of 134 different quinones, probing their 1 e– reduction potentials, pKa values, and 2 e–/2 H+ reduction potentials. The density functional theory calculations reveal an approximately linear correlation between these three properties and an effective Hammett constant associated with the quinone substituent(s). However, deviations from this linear scaling relationship are evident for quinones that feature intramolecular hydrogen bonding in the hydroquinone, halogen substituents, charged substituents, and/or sterically bulky substituents. These results, particularly the different substituent effects on the 1 e– versus 2 e–/2 H+ reduction potentials, have important implications for designing quinones with tailored redox properties.

Nature employs a TyrZ-His pair as a redox relay that couples proton transfer to the redox process between P680 and the water oxidizing catalyst in photosystem II. Artificial redox relays composed of different benzimidazole–phenol dyads (benzimidazole models His and phenol models Tyr) with substituents designed to simulate the hydrogen bond network surrounding the TyrZ-His pair have been prepared. When the benzimidazole substituents are strong proton acceptors such as primary or tertiary amines, theory predicts that a concerted two proton transfer process associated with the electrochemical oxidation of the phenol will take place. Also, theory predicts a decrease in the redox potential of the phenol by ∼300 mV and a small kinetic isotope effect (KIE). Indeed, electrochemical, spectroelectrochemical, and KIE experimental data are consistent with these predictions. Notably, these results were obtained by using theory to guide the rational design of artificial systems and have implications for managing proton activity to optimize efficiency at energy conversion sites involving water oxidation and reduction.

Bioinspired constructs consisting of benzimidazole-phenol moieties bearing N-phenylimines as proton-accepting substituents have been designed to mimic the H-bond network associated with the TyrZ-His190 redox relay in photosystem II. These compounds provide a platform to theoretically and experimentally explore and expand proton-coupled electron transfer (PCET) processes. The models feature H-bonds between the phenol and the nitrogen at the 3-position of the benzimidazole and between the 1H-benzimidazole proton and the imine nitrogen. Protonation of the benzimidazole and the imine can be unambiguously detected by infrared spectroelectrochemistry (IRSEC) upon oxidation of the phenol. DFT calculations and IRSEC results demonstrate that with sufficiently strong electron-donating groups at the para-position of the N-phenylimine group (e.g.,-OCH3 substitution), proton transfer to the imine is exergonic upon phenol oxidation, leading to a oneelectron, two-proton (E2PT) product with the imidazole acting as a proton relay. When transfer of the second proton is not sufficiently exergonic (e.g.,-CN substitution), a one-electron, one-proton transfer (EPT) product is dominant. Thus, the extent of proton translocation along the H-bond network, either ~1.6 Å or ~6.4 Å, can be controlled through imine substitution. Moreover, the H-bond strength between the benzimidazole NH and the imine nitrogen, which is a function of their relative pKa values, and the redox potential of the phenoxyl radical/phenol couple are linearly correlated with the Hammett constants of the substituents. In all cases, a high potential (~1 V vs SCE) is observed for the phenoxyl radical/phenol couple. Designing and tuning redox-coupled proton wires is important for understanding bioenergetics and developing novel artificial photosynthetic systems.

A new class of synthetic models for the active site of [NiFe]-hydrogenases are described. The NiI/II(SCys)2 and FeII(CN)2CO sites are represented with (RC5H4)NiI/II and FeII(diphos)(CO) modules, where diphos = 1,2-C2H4(PPh2)2(dppe) or cis-1,2-C2H2(PPh2)2(dppv). The two bridging thiolate ligands are represented by CH2(CH2S)22− (pdt2−), Me2C(CH2S)22− (Me2pdt2−), and (C6H5S)22−. The reaction of Fe(pdt)(CO)2(dppe) and [(C5H5)3Ni2]BF4 affords [(C5H5)Ni(pdt)Fe(dppe)-(CO)]BF4 ([1a]BF4). Monocarbonyl [1a]BF4 features an S = 0 NiIIFeII center with five-coordinated iron, as proposed for the Ni-SIa state of the enzyme. One-electron reduction of [1a]+ affords the S = 1/2 derivative [1a]0, which, according to density functional theory (DFT) calculations and electron paramagnetic resonance and Mössbauer spectroscopies, is best described as a NiIFeII compound. The NiIFeII assignment matches that for the Ni-L state in [NiFe]-hydrogenase, unlike recently reported NiIIFeI-based models. Compound [1a]0 reacts with strong acids to liberate 0.5 equiv of H2 and regenerate [1a]+, indicating that H2 evolution is catalyzed by [1a]0. DFT calculations were used to investigate the pathway for H2 evolution and revealed that the mechanism can proceed through two isomers of [1a]0 that differ in the stereochemistry of the Fe(dppe)CO center. Calculations suggest that protonation of [1a]0 (both isomers) affords NiIII–H–FeII intermediates, which represent mimics of the Ni-C state of the enzyme.

Proton-coupled electron transfer (PCET) combines the movement of fundamental charged species to form an essential link between electron- and proton-transport reactions in bioenergetics and catalysis in general. The length scale over which proton transport may occur within PCET processes and the thermodynamic consequences of the resulting proton chemical potential to the oxidation reaction driving these PCET processes have not been generally established. Here we report the design of bioinspired molecules that employ oxidation–reduction processes to move reversibly two, three, and four protons via a Grotthuss-type mechanism along hydrogen-bonded networks up to ∼16 Å in length. These molecules are composed of benzimidazole moieties linking a phenol to the final proton acceptor, a cyclohexylimine. Following electrochemical oxidation of the phenol, the appearance of an infrared band at 1660 cm–1 signals proton arrival at the terminal basic site. Switching the electrode potential to reducing conditions reverses the proton translocation and resets the structure to the initial species. In addition to mimicking the first step of the iconic PCET process used by the Tyr z -His190 redox relay in photosystem II to oxidize water, this work specifically addresses theoretically and experimentally the length scale over which PCET processes may occur. The thermodynamic findings from these redox-driven, bioinspired “proton wires” have implications for understanding and rationally designing pumps for the generation of proton-motive force in artificial and reengineered photosynthesis, as well as for management of proton activity around catalytic sites, including those for water oxidation and oxygen reduction.

Theory and experiment indicate that the protonation of reduced NiFe dithiolates proceeds via a previously undetected isomer with enhanced basicity. In particular, it is proposed that protonation of (OC)3Fe(pdt)Ni(dppe) (1; pdt2– = –S(CH2)3S–; dppe = Ph2P(CH2)2PPh2) occurs at the Fe site of the two-electron mixed-valence Fe(0)Ni(II) species, not the Fe(I)-Ni(I) bond for the homovalence isomer of 1. The new pathway, which may have implications for protonation of other complexes and clusters, was uncovered through studies on the homologous series L(OC)2Fe(pdt)M(dppe), where M = Ni, Pd (2), and Pt (3) and L = CO, PCy3. Similar to 1, complexes 2 and 3 undergo both protonation and 1e– oxidation to afford well-characterized hydrides ([2H]+ and [3H]+) and mixed-valence derivatives ([2]+ and [3]+), respectively. Whereas the Pd site is tetrahedral in 2, the Pt site is square-planar in 3, indicating that this complex is best described as Fe(0)Pt(II). In view of the results on 2 and 3, the potential energy surface of 1 was reinvestigated with density functional theory. These calculations revealed the existence of an energetically accessible and more basic Fe(0)Ni(II) isomer with a square-planar Ni site.

The intermediacy of a reduced nickel–iron hydride in hydrogen evolution catalyzed by Ni–Fe complexes was verified experimentally and computationally. In addition to catalyzing hydrogen evolution, the highly basic and bulky (dppv)Ni(μ-pdt)Fe(CO)(dppv) ([1]0; dppv = cis-C2H2(PPh2)2) and its hydride derivatives have yielded to detailed characterization in terms of spectroscopy, bonding, and reactivity. The protonation of [1]0 initially produces unsym-[H1]+, which converts by a first-order pathway to sym-[H1]+. These species have C1 (unsym) and Cs (sym) symmetries, respectively, depending on the stereochemistry of the octahedral Fe site. Both experimental and computational studies show that [H1]+ protonates at sulfur. The S = 1/2 hydride [H1]0 was generated by reduction of [H1]+ with Cp*2Co. Density functional theory (DFT) calculations indicate that [H1]0 is best described as a Ni(I)–Fe(II) derivative with significant spin density on Ni and some delocalization on S and Fe. EPR spectroscopy reveals both kinetic and thermodynamic isomers of [H1]0. Whereas [H1]+ does not evolve H2 upon protonation, treatment of [H1]0 with acids gives H2. The redox state of the “remote” metal (Ni) modulates the hydridic character of the Fe(II)–H center. As supported by DFT calculations, H2 evolution proceeds either directly from [H1]0 and external acid or from protonation of the Fe–H bond in [H1]0 to give a labile dihydrogen complex. Stoichiometric tests indicate that protonation-induced hydrogen evolution from [H1]0 initially produces [1]+, which is reduced by [H1]0. Our results reconcile the required reductive activation of a metal hydride and the resistance of metal hydrides toward reduction. This dichotomy is resolved by reduction of the remote (non-hydride) metal of the bimetallic unit.