FeMoco Research Articles

Electronic Structure Based Intuitive Design Principle of Single‐Atom Catalysts for Efficient Electrolytic Nitrogen Reduction

AbstractAs an alternative to cost‐ and energy intensive Haber‐Bosch process, the implementation of electrolytic ammonia synthesis from dinitrogen molecule has been a long‐sought goal. State‐of‐the‐art electrocatalysts for nitrogen reduction reaction (NRR) face not only activity but also selectivity problem with the competitive hydrogen evolution reaction (HER). Recently, single‐atom catalysts (SACs) have emerged as promising for various reactions as they combine the best of homogenous and heterogenous catalysts. The reason for their high activity compared to their bulk and nanoparticle counterparts are yet to be completely understood. Inspired by the structure of nitrogenase FeMo cofactor, here we studied 13 transition metals anchored on MoS2 monolayer at Mo‐top positions, as possible electrolytic NRR catalysts using first‐principles methods. Employing the implicit solvation model, we calculated free energy barriers for proton abstraction by N2 molecule in end‐on configuration and adsorption free energy of hydrogen on all SACs. Based on these two parameters, Fe, Co, and Ru were found to be the most active and highly selective electrolytic NRR catalysts. Compared with other mechanisms, the limiting potentials (and hence activity) for enzymatic mechanism were found to be higher on these three SACs, with Ru SAC having a very low overpotential of 0.38 V vs SHE. Bader charge transferred from transition metal to N2 molecule and group number of transition metals correlate strongly with the NRR activity and hence emerge as two key descriptors for catalytic activity. These intuitive principles for rational designing of promising alternatives to the currently used bulk Ru(0001) catalyst could accelerate the search for highly efficient and selective SACs for electrolytic NRR.

Bioassembly of complex iron–sulfur enzymes: hydrogenases and nitrogenases

Nature uses multinuclear metal clusters to catalyse a number of important multielectron redox reactions. Examples that employ complex Fe-S clusters in catalysis include the Fe-Mo cofactor (FeMoco) of nitrogenase and its V and all-Fe variants, and the [FeFe] and [NiFe] hydrogenases. This Perspective begins with a focus on the catalytic H-cluster of [FeFe] hydrogenase, which is highly active in producing molecular H2. There has been much recent progress in characterizing the enzyme-catalysed assembly of the H-cluster, including information gleaned from spectroscopy combined with in vitro isotopic labelling of this cluster using chemical synthesis. We then compare the lessons learned from H-cluster biosynthesis to what is known about the bioassembly of the binuclear active site of [NiFe] hydrogenase and the nitrogenase active site cluster FeMoco.

Delicate dance becomes a ballet

Metalloenzymes The enzyme nitrogenase uses adenosine triphosphate and several unusual iron-sulfur cofactors to pump electrons into typically inert dinitrogen (N2), providing protons along the way. Previous work has shown that sulfur atoms in the iron-molybdenum cofactor (FeMoCo) are labile and suggests that replacement of one of the sulfurs by N2 is integral to the mechanism of N2 binding and reduction. Through the elimination of excess reducing agent during preparation, Kang et al. determined structures of Mo-nitrogenase in a resting conformation. Unexpectedly, they found that all three sulfurs at the outer edge of FeMoCo appear to be labile, with one subunit even having two of three sulfurs replaced by light, diatomic ligands. Biochemical and spectroscopic data indicate that the protein is active, holds tightly bound N2, and is in the expected oxidation state. These results may prompt a reassessment of the possible mechanisms of N2 reduction and the role of dynamic belt ligands in FeMoCo. Science , this issue p. [1381][1] [1]: /lookup/doi/10.1126/science.aaz6748

Structural evidence for a dynamic metallocofactor during N2 reduction by Mo-nitrogenase.

The enzyme nitrogenase uses a suite of complex metallocofactors to reduce dinitrogen (N2) to ammonia. Mechanistic details of this reaction remain sparse. We report a 1.83-angstrom crystal structure of the nitrogenase molybdenum-iron (MoFe) protein captured under physiological N2 turnover conditions. This structure reveals asymmetric displacements of the cofactor belt sulfurs (S2B or S3A and S5A) with distinct dinitrogen species in the two αβ dimers of the protein. The sulfur-displaced sites are distinct in the ability of protein ligands to donate protons to the bound dinitrogen species, as well as the elongation of either the Mo-O5 (carboxyl) or Mo-O7 (hydroxyl) distance that switches the Mo-homocitrate ligation from bidentate to monodentate. These results highlight the dynamic nature of the cofactor during catalysis and provide evidence for participation of all belt-sulfur sites in this process.

Atomically embedded asymmetrical dual-metal dimers on N-doped graphene for ultra-efficient nitrogen reduction reaction

The atomically dispersed metal species on nitrogen-doped graphene nanosheets have exhibited impressive catalytic properties towards oxygen evolution, oxygen reduction and carbon dioxide reactions (OER/ORR/CRR), but poor performances for nitrogen reduction reactions (NRR). The main reason is ascribed to the sluggish kinetics of the first and last proton-coupled electron transfer (ET) on the unitary single-atom site. In this work, an asymmetrical dual-metal dimer catalytic center, which is inspired by the active sites of natural enzymes, such as nitrogenases, that efficiently catalyze the reduction of N2 to NH3 through FeMo cofactors, is theoretically reported. Remarkably, the density functional theory (DFT) calculations showed that the random combination of two non-precious metal atoms such as Fe, Co, Mo, W and Ru to form catalytically active bimetallic sites lead to a remarkable reduction of about two times of the first or last hydrogenation free energy barrier step. The resulting Mo-Ru, Mo-Co, Mo-W, Mo-Fe and Fe-Ru dimers exhibited ultra-low onset potentials of only 0.17, 0.27, 0.28, 0.36 and 0.39 V, respectively. Meanwhile, the HER side reaction can be well suppressed during the NRR. The superior catalytic performance in the bimetallic clusters is mainly attributed to both the electron donation from the asymmetrical metal atoms to the terminal side-on of N2 molecules, which significantly polarizes and weakens the N≡N bond, and to the synergistic effect of the dual-metal dimers that moderates the binding strength of the key intermediates. This work constitutes the first DFT study of the N2 electroreduction processes on dual-metal dimer catalytic sites and, consequently, paves the way towards the rational design of highly efficient hetero-bimetallic NRR electrocatalysts.

Bond-valence analyses of the crystal structures of FeMo/V cofactors in FeMo/V proteins.

The bond-valence method has been used for valence calculations of FeMo/V cofactors in FeMo/V proteins using 51 crystallographic data sets of FeMo/V proteins from the Protein Data Bank. The calculations show molybdenum(III) to be present in MoFe7S9C(Cys)(HHis)[R-(H)homocit] (where H4homocit is homocitric acid, HCys is cysteine and HHis is histidine) in FeMo cofactors, while vanadium(III) with a more reduced iron complement is obtained for FeV cofactors. Using an error analysis of the calculated valences, it was found that in FeMo cofactors Fe1, Fe6 and Fe7 can be unambiguously assigned as iron(III), while Fe2, Fe3, Fe4 and Fe5 show different degrees of mixed valences for the individual Fe atoms. For the FeV cofactors in PDB entry 5n6y, Fe4, Fe5 and Fe6 correspond to iron(II), iron(II) and iron(III), respectively, while Fe1, Fe2, Fe3 and Fe7 exhibit strongly mixed valences. Special situations such as CO-bound and selenium-substituted FeMo cofactors and O(N)H-bridged FeV cofactors are also discussed and suggest rearrangement of the electron configuration on the substitution of the bridging S atoms.

Features of Anabaena PCC 7120ΔHUP Mutants with Amino Acid Substitutions in Nitrogenase

Mutant strains of the filamentous cyanobacterium Anabaena strain PCC 7120 ΔHup (dc-Q193S and dc-R284H) with amino acid substitutions located in the vicinity of the FeMo cofactor of nitrogenase possess nitrogenase activity with a hydrogen production rate of approximately 18 μmol Н2/(mg h), which is ~30% lower than that of the parental strain ΔHup. The photosynthetic activity of mutants is also reduced. Unlike the parental strain ΔHup, the dc-Q193S mutant shows a lower temperature optimum for hydrogen photoproduction. This difference is probably due to the lowered filament strength (fragmentation). Hydrogen photoproduction in mutants does not significantly differ from that of the parental strain in relation to the activation energy, light saturation constants (41–62 μmol quanta /(m2 s)), and acetylene-induced inhibition. However, in contrast to the parental strain, hydrogen photoproduction in the mutant strains is not inhibited by molecular nitrogen, i.e., amino acid substitutions cause significant changes in the reaction requiring eight electrons (N2 fixation). The possibility to use nitrogen or atmospheric air instead of argon in the hydrogen production is promising from the practical point of view, though reduced activity and increased fragility of filaments in the studied mutants limit the possibility of their practical use.

Electron Paramagnetic Resonance and Magnetic Circular Dichroism Spectra of the Nitrogenase M Cluster Precursor Suggest Sulfur Migration upon Oxidation: A Proposal for Substrate and Inhibitor Binding

The active site of the nitrogen-fixing enzyme Mo-nitrogenase is the M cluster ([MoFe7 S9 C⋅R-homocitrate]), also known as the FeMo cofactor or FeMoco. The biosynthesis of this highly complex metallocluster involves a series of proteins. Among them, NifB, a radical-SAM enzyme, is instrumental in the assembly of the L cluster ([Fe8 S9 C]), a precursor and all-iron core of the M cluster. In the absence of sulfite, NifB assembles a precursor form of the L cluster called the L* cluster ([Fe8 S8 C]), which lacks the final ninth sulfur. EPR and MCD spectroscopies are used to probe the electronic structures of the paramagnetic, oxidized forms of both the L and L* clusters, labeled LOx and [L*]Ox . This study shows that both LOx and [L*]Ox have nearly identical EPR and MCD spectra, thus suggesting that the two clusters have identical structures upon oxidation; in other words, a sulfur migrates away from LOx following oxidation, thereby rendering the cluster identical to [L*]Ox . It is proposed that a similar migration could occur to the M cluster upon oxidation, and that this is an instrumental part of both M cluster formation and nitrogenase substrate/inhibitor binding.

Nitrogenase Bioelectrochemistry for Synthesis Applications

The fixation of atmospheric dinitrogen to ammonia by industrial technologies (such as the Haber Bosch process) has revolutionized humankind. In contrast to industrial technologies, a single enzyme is known for its ability to reduce or "fix" dinitrogen: nitrogenase. Nitrogenase is a complex oxidoreductase enzymatic system that includes a catalytic protein (where dinitrogen is reduced) and an electron-transferring reductase protein (termed the Fe protein) that delivers the electrons necessary for dinitrogen fixation. The catalytic protein most commonly contains a FeMo cofactor (called the MoFe protein), but it can also contain a VFe or FeFe cofactor. Besides their ability to fix dinitrogen to ammonia, these nitrogenases can also reduce substrates such as carbon dioxide to formate. Interestingly, the VFE nitrogenase can also form carbon-carbon bonds. The vast majority of research surrounding nitrogenase employs the Fe protein to transfer electrons, which is also associated with the rate-limiting step of nitrogenase catalysis and also requires the hydrolysis of adenosine triphosphate. Thus, there is significant interest in artificially transferring electrons to the catalytic nitrogenase proteins. In this Account, we review nitrogenase electrocatalysis whereby electrons are delivered to nitrogenase from electrodes. We first describe the use of an electron mediator (cobaltocene) to transfer electrons from electrodes to the MoFe protein. The reduction of protons to molecular hydrogen was realized, in addition to azide and nitrite reduction to ammonia. Bypassing the rate-limiting step within the Fe protein, we also describe how this approach was used to interrogate the rate-limiting step of the MoFe protein: metal-hydride protonolysis at the FeMo-co. This Account next reviews the use of cobaltocene to mediate electron transfer to the VFe protein, where the reduction of carbon dioxide and the formation of carbon-carbon bonds (yielding the formation of ethene and propene) was realized. This approach also found success in mediating electron transfer to the FeFe catalytic protein, which exhibited improved carbon dioxide reduction in comparison to the MoFe protein. In the final example of mediated electron transfer to the catalytic protein, this Account also reviews recent work where the coupling of infrared spectroscopy with electrochemistry enabled the potential-dependent binding of carbon monoxide to the FeMo-co to be studied. As an alternative to mediated electron transfer, recent work that has sought to transfer electrons to the catalytic proteins in the absence of electron mediators (by direct electron transfer) is also reviewed. This approach has subsequently enabled a thermodynamic landscape to be proposed for the cofactors of the catalytic proteins. Finally, this Account also describes nitrogenase electrocatalysis whereby electrons are first transferred from an electrode to the Fe protein, before being transferred to the MoFe protein alongside the hydrolysis of adenosine triphosphate. In this way, increased quantities of ammonia can be electrocatalytically produced from dinitrogen fixation. We discuss how this has led to the further upgrade of electrocatalytically produced ammonia, in combination with additional enzymes (diaphorase, alanine dehydrogenase, and transaminase), to selective production of chiral amine intermediates for pharmaceuticals. This Account concludes by discussing current and future research challenges in the field of electrocatalytic nitrogen fixation by nitrogenase.

Electrochemical Characterization of Isolated Nitrogenase Cofactors from Azotobacter vinelandii.

The nitrogenase cofactors are structurally and functionally unique in biological chemistry. Despite a substantial amount of spectroscopic characterization of protein-bound and isolated nitrogenase cofactors, electrochemical characterization of these cofactors and their related species is far from complete. Herein we present voltammetric studies of three isolated nitrogenase cofactor species: the iron-molybdenum cofactor (M-cluster), iron-vanadium cofactor (V-cluster), and a homologue to the iron-iron cofactor (L-cluster). We observe two reductive events in the redox profiles of all three cofactors. Of the three, the V-cluster is the most reducing. The reduction potentials of the isolated cofactors are significantly more negative than previously measured values within the molybdenum-iron and vanadium-iron proteins. The outcome of this study provides insight into the importance of the heterometal identity, the overall ligation of the cluster, and the impact of the protein scaffolds on the overall electronic structures of the cofactors.

Electronic landscape of the P-cluster of nitrogenase as revealed through many-electron quantum wavefunction simulations.

The electronic structure of the nitrogenase metal cofactors is central to nitrogen fixation. However, the P-cluster and FeMo cofactor, each containing eight Fe atoms, have eluded detailed characterization of their electronic properties. We report on the low-energy electronic states of the P-cluster in three oxidation states through exhaustive many-electron wavefunction simulations enabled by new theoretical methods. The energy scales of orbital and spin excitations overlap, yielding a dense spectrum with features that we trace to the underlying atomic states and recouplings. The clusters exist in superpositions of spin configurations with non-classical spin correlations, complicating interpretation of magnetic spectroscopies, whereas the charges are mostly localized from reorganization of the cluster and its surroundings. On oxidation, the opening of the P-cluster substantially increases the density of states, which is intriguing given its proposed role in electron transfer. These results demonstrate that many-electron simulations stand to provide new insights into the electronic structure of the nitrogenase cofactors.

Controlled Incorporation of Nitrides into W‐Fe‐S Clusters

AbstractIncorporation of monatomic 2p ligands into the core of iron–sulfur clusters has been researched since the discovery of interstitial carbide in the FeMo cofactor of Mo‐dependent nitrogenase, but has proven to be a synthetic challenge. Herein, two distinct synthetic pathways are rationalized to install nitride ligands into targeted positions of W‐Fe‐S clusters, generating unprecedented nitride‐ligated iron–sulfur clusters, namely [(Tp*)2W2Fe6(μ4‐N)2S6L4]2− (Tp*=tris(3,5‐dimethyl‐1‐pyrazolyl)hydroborate(1−), L=Cl− or Br−). 57Fe Mössbauer study discloses metal oxidation states of WIV2FeII4FeIII2 with localized electron distribution, which is analogous to the mid‐valent iron centres of FeMo cofactor at resting state. Good agreement of Mössbauer data with the empirical linear relationship for Fe–S clusters indicates similar ligand behaviour of nitride and sulfide in such clusters, providing useful reference for reduced nitrogen in a nitrogenase‐like environment.

Controlled Incorporation of Nitrides into W-Fe-S Clusters.

Incorporation of monatomic 2p ligands into the core of iron-sulfur clusters has been researched since the discovery of interstitial carbide in the FeMo cofactor of Mo-dependent nitrogenase, but has proven to be a synthetic challenge. Herein, two distinct synthetic pathways are rationalized to install nitride ligands into targeted positions of W-Fe-S clusters, generating unprecedented nitride-ligated iron-sulfur clusters, namely [(Tp*)2 W2 Fe6 (μ4 -N)2 S6 L4 ]2- (Tp*=tris(3,5-dimethyl-1-pyrazolyl)hydroborate(1-), L=Cl- or Br- ). 57 Fe Mössbauer study discloses metal oxidation states of WIV2 FeII4 FeIII2 with localized electron distribution, which is analogous to the mid-valent iron centres of FeMo cofactor at resting state. Good agreement of Mössbauer data with the empirical linear relationship for Fe-S clusters indicates similar ligand behaviour of nitride and sulfide in such clusters, providing useful reference for reduced nitrogen in a nitrogenase-like environment.

Spectroscopic Description of the E1 State of Mo Nitrogenase Based on Mo and Fe X-ray Absorption and Mössbauer Studies.

Mo nitrogenase (N2ase) utilizes a two-component protein system, the catalytic MoFe and its electron-transfer partner FeP, to reduce atmospheric dinitrogen (N2) to ammonia (NH3). The FeMo cofactor contained in the MoFe protein serves as the catalytic center for this reaction and has long inspired model chemistry oriented toward activating N2. This field of chemistry has relied heavily on the detailed characterization of how Mo N2ase accomplishes this feat. Understanding the reaction mechanism of Mo N2ase itself has presented one of the most challenging problems in bioinorganic chemistry because of the ephemeral nature of its catalytic intermediates, which are difficult, if not impossible, to singly isolate. This is further exacerbated by the near necessity of FeP to reduce native MoFe, rendering most traditional means of selective reduction inept. We have now investigated the first fundamental intermediate of the MoFe catalytic cycle, E1, as prepared both by low-flux turnover and radiolytic cryoreduction, using a combination of Mo Kα high-energy-resolution fluorescence detection and Fe K-edge partial-fluorescence-yield X-ray absorption spectroscopy techniques. The results demonstrate that the formation of this state is the result of an Fe-centered reduction and that Mo remains redox-innocent. Furthermore, using Fe X-ray absorption and 57Fe Mössbauer spectroscopies, we correlate a previously reported unique species formed under cryoreducing conditions to the natively formed E1 state through annealing, demonstrating the viability of cryoreduction in studying the catalytic intermediates of MoFe.

Localized Electronic Structure of Nitrogenase FeMoco Revealed by Selenium K-Edge High Resolution X-ray Absorption Spectroscopy.

The size and complexity of Mo-dependent nitrogenase, a multicomponent enzyme capable of reducing dinitrogen to ammonia, have made a detailed understanding of the FeMo cofactor (FeMoco) active site electronic structure an ongoing challenge. Selective substitution of sulfur by selenium in FeMoco affords a unique probe wherein local Fe–Se interactions can be directly interrogated via high-energy resolution fluorescence detected X-ray absorption spectroscopic (HERFD XAS) and extended X-ray absorption fine structure (EXAFS) studies. These studies reveal a significant asymmetry in the electronic distribution of the FeMoco, suggesting a more localized electronic structure picture than is typically assumed for iron–sulfur clusters. Supported by experimental small molecule model data in combination with time dependent density functional theory (TDDFT) calculations, the HERFD XAS data is consistent with an assignment of Fe2/Fe6 as an antiferromagnetically coupled diferric pair. HERFD XAS and EXAFS have also been applied to Se-substituted CO-inhibited MoFe protein, demonstrating the ability of these methods to reveal electronic and structural changes that occur upon substrate binding. These results emphasize the utility of Se HERFD XAS and EXAFS for selectively probing the local electronic and geometric structure of FeMoco.

Genetic and Biochemical Analysis of the Azotobacter vinelandii Molybdenum Storage Protein.

The N2 fixing bacterium Azotobacter vinelandii carries a molybdenum storage protein, referred to as MoSto, able to bind 25-fold more Mo than needed for maximum activity of its Mo nitrogenase. Here we have investigated a plausible role of MoSto as obligate intermediate in the pathway that provides Mo for the biosynthesis of nitrogenase iron–molybdenum cofactor (FeMo-co). The in vitro FeMo-co synthesis and insertion assay demonstrated that purified MoSto functions as Mo donor and that direct interaction with FeMo-co biosynthetic proteins stimulated Mo donation. The phenotype of an A. vinelandii strain lacking the MoSto subunit genes (ΔmosAB) was analyzed. Consistent with its role as storage protein, the ΔmosAB strain showed severe impairment to accumulate intracellular Mo and lower resilience than wild type to Mo starvation as demonstrated by decreased in vivo nitrogenase activity and competitive growth index. In addition, it was more sensitive than the wild type to diazotrophic growth inhibition by W. The ΔmosAB strain was found to readily derepress vnfDGK upon Mo step down, in contrast to the wild type that derepressed Vnf proteins only after prolonged Mo starvation. The ΔmosAB mutation was then introduced in a strain lacking V and Fe-only nitrogenase structural genes (Δvnf Δanf) to investigate possible compensations from these alternative systems. When grown in Mo-depleted medium, the ΔmosAB and mosAB+ strains showed low but similar nitrogenase activities regardless of the presence of Vnf proteins. This study highlights the selective advantage that MoSto confers to A. vinelandii in situations of metal limitation as those found in many soil ecosystems. Such a favorable trait should be included in the gene complement of future nitrogen fixing plants.

The bacterial MrpORP is a novel Mrp/NBP35 protein involved in iron-sulfur biogenesis

Despite recent advances in understanding the biogenesis of iron-sulfur (Fe-S) proteins, most studies focused on aerobic bacteria as model organisms. Accordingly, multiple players have been proposed to participate in the Fe-S delivery step to apo-target proteins, but critical gaps exist in the knowledge of Fe-S proteins biogenesis in anaerobic organisms. Mrp/NBP35 ATP-binding proteins are a subclass of the soluble P-loop containing nucleoside triphosphate hydrolase superfamily (P-loop NTPase) known to bind and transfer Fe-S clusters in vitro. Here, we report investigations of a novel atypical two-domain Mrp/NBP35 ATP-binding protein named MrpORP associating a P-loop NTPase domain with a dinitrogenase iron-molybdenum cofactor biosynthesis domain (Di-Nase). Characterization of full length MrpORP, as well as of its two domains, showed that both domains bind Fe-S clusters. We provide in vitro evidence that the P-loop NTPase domain of the MrpORP can efficiently transfer its Fe-S cluster to apo-target proteins of the ORange Protein (ORP) complex, suggesting that this novel protein is involved in the maturation of these Fe-S proteins. Last, we showed for the first time, by fluorescence microscopy imaging a polar localization of a Mrp/NBP35 protein.

Cyclophanes as Platforms for Reactive Multimetallic Complexes.

Multimetallic cofactors supported by weak-field donors frequently function as reaction centers in metalloproteins, and many of these cofactors catalyze small molecule activation (e.g., N2, O2, CO2) with prominent roles in geochemical element cycles or detoxification. Notable examples include the iron-molybdenum cofactor of the molybdenum-dependent nitrogenases, which catalyze N2 fixation, and the NiFe4S4 cluster and the Mo(O)SCu site in various carbon monoxide dehydrogenases. The prevailing proposed reaction mechanisms for these multimetallic cofactors relies on a cooperative pathway, in which the oxidation state changes are distributed over the aggregate coupled with orbital overlap between the substrate and more than one metal ion within the cluster. Such cooperativity has also been proposed for chemical transformations at the surfaces of heterogeneous catalysts. However, the design details that afford cooperative effects and allow such reactivity to be harnessed effectively in homogeneous synthetic systems remain unclear. Relatedly, hydride donors ligated to these metal cluster cofactors are suggested as precursors to the state that reacts with substrates; here too, however, the reactivity of hydride-decorated clusters supported by weak-field ligands is underexplored. Inspired by the reactivity potential of multimetallic assemblies evidenced in biological systems, approaches to design, synthesize, and evaluate reactivity of polynuclear metal compounds have been actively explored. In a similar vein to the templating function afforded by enzyme active sites, a carefully engineered organic ligand can be employed to control metal nuclearity of the complex and the local coordination environment of each metal center. This Account presents our efforts within this field, beginning with ligand design considerations followed by a survey of observed small molecule activation by trimetallic cyclophanates. We highlight the distinct reactivity outcomes accessed by multimetallic compounds as compared to aggregates that assemble in reaction mixtures from monometallic precursors. Contributing to the opportunity for programmed cooperativity in these designed multimetallic compounds, the cyclophane also dictates the orientation of substrate binding and metal-substrate interactions, which has a prominent influence on reactivity. For example, the dinitrogen-tricopper(I) cyclophanate reacts with dioxygen with markedly different results as compared to monocopper compounds. As an unexpected outcome, one series of tricopper compounds were discovered to be competent catalysts for carbon dioxide reduction to oxalate-a formally one-electron process-hinting at an inherently broader reaction scope for weak-field clusters at lowering the barrier for one-electron pathways as well as multielectron redox transformations. Further reflecting the role of the ligand in tuning reactivity, the trimetallic trihydride cluster compounds, [M3(μ-H)3]3+ (M = FeII, CoII, ZnII), demonstrate substrate specificity for CO2 over various other unsaturated molecules and surprising stability toward water. This series reflects the role of the local environment of a shallow ligand pocket to control substrate access. Summed together, the systems described here evidence the anticipated cooperative reactivity accessed in designed multimetallic species vs self-assembled monometallic systems (e.g., O2 activation and O atom transfer) as well as control of substrate access by seemingly subtle structural effects. Indeed, future efforts aim to interrogate the limits of cooperativity in these systems as well as the role of ligand dynamics and sterics on reactivity.

The electronic complexity of the ground-state of the FeMo cofactor of nitrogenase as relevant to quantum simulations.

We report that a recent active space model of the nitrogenase FeMo cofactor, proposed in the context of simulations on quantum computers, is not representative of the electronic structure of the FeMo cofactor ground-state. A more representative model does not affect much certain resource estimates for a quantum computer such as the cost of a Trotter step, while strongly affecting others such as the cost of adiabatic state preparation. Thus, conclusions should not be drawn from the complexity of quantum or classical simulations of the electronic structure of this system in this active space. We provide a different model active space for the FeMo cofactor that contains the basic open-shell qualitative character, which may be useful as a benchmark system for making resource estimates for classical and quantum computers.

Coordinated regulation of nitrogen fixation and molybdate transport by molybdenum.

Biological nitrogen fixation, the reduction of chemically inert dinitrogen to bioavailable ammonia, is a central process in the global nitrogen cycle highly relevant for life on earth. N2 reduction to NH3 is catalyzed by nitrogenases exclusively synthesized by diazotrophic prokaryotes. All diazotrophs have a molybdenum nitrogenase containing the unique iron-molybdenum cofactor FeMoco. In addition, some diazotrophs encode one or two alternative Mo-free nitrogenases that are less efficient at reducing N2 than Mo-nitrogenase. To permit biogenesis of Mo-nitrogenase and other molybdoenzymes when Mo is scarce, bacteria synthesize the high-affinity molybdate transporter ModABC. Generally, Mo supports expression of Mo-nitrogenase genes, while it represses production of Mo-free nitrogenases and ModABC. Since all three nitrogenases and ModABC can reach very high levels at suitable Mo concentrations, tight Mo-mediated control saves considerable resources and energy. This review outlines the similarities and differences in Mo-responsive regulation of nitrogen fixation and molybdate transport in diverse diazotrophs.