Nitrogen fixation, the six-electron/six-proton reduction of N2, to give NH3, is one of the most challenging and important chemical transformations. Notwithstanding the barriers associated with this ...reaction, significant progress has been made in developing molecular complexes that reduce N2 into its bioavailable form, NH3. This progress is driven by the dual aims of better understanding biological nitrogenases and improving upon industrial nitrogen fixation. In this review, we highlight both mechanistic understanding of nitrogen fixation that has been developed, as well as advances in yields, efficiencies, and rates that make molecular alternatives to nitrogen fixation increasingly appealing. We begin with a historical discussion of N2 functionalization chemistry that traverses a timeline of events leading up to the discovery of the first bona fide molecular catalyst system and follow with a comprehensive overview of d-block compounds that have been targeted as catalysts up to and including 2019. We end with a summary of lessons learned from this significant research effort and last offer a discussion of key remaining challenges in the field.
Delivering protons with electrons
Many chemical reactions involve concurrent transfer of a proton and an electron. In electrochemical synthesis, this mechanism could prove useful in lowering the ...energy necessary for cathodic electron transfer alone, but it is hindered by competing direct coupling of the protons and electrons to make hydrogen instead. Chalkley
et al.
now report a molecular mediator consisting of a dimethylaniline base tethered to a cobaltocenium electron acceptor. This construct can deliver both a proton and an electron to a substrate from an acid and a cathode while skirting the hydrogen pathway.
Science
, this issue p.
850
A cobaltocene complex tethered to dimethylaniline transfers electrons from a cathode to a substrate concurrently with protons.
Electrocatalytic approaches to the activation of unsaturated substrates via reductive concerted proton-electron transfer (CPET) must overcome competing, often kinetically dominant hydrogen evolution. We introduce the design of a molecular mediator for electrochemically triggered reductive CPET through the synthetic integration of a Brønsted acid and a redox mediator. Cathodic reduction at the cobaltocenium redox mediator substantially weakens the homolytic nitrogen-hydrogen bond strength of a Brønsted acidic anilinium tethered to one of the cyclopentadienyl rings. The electrochemically generated molecular mediator is demonstrated to transform a model substrate, acetophenone, to its corresponding neutral α-radical via a rate-determining CPET.
New electrochemical ammonia (NH
) synthesis technologies are of interest as a complementary route to the Haber-Bosch process for distributed fertilizer generation, and towards exploiting ammonia as a ...zero-carbon fuel produced via renewably sourced electricity
. Apropos of these goals is a surge of fundamental research targeting heterogeneous materials as electrocatalysts for the nitrogen reduction reaction (N
RR)
. These systems generally suffer from poor stability and NH
selectivity; the hydrogen evolution reaction (HER) outcompetes N
RR
. Molecular catalyst systems can be exquisitely tuned and offer an alternative strategy
, but progress has been thwarted by the same selectivity issue; HER dominates. Here we describe a tandem catalysis strategy that offers a solution to this puzzle. A molecular complex that can mediate an N
reduction cycle is partnered with a co-catalyst that interfaces the electrode and an acid to mediate proton-coupled electron transfer steps, facilitating N-H bond formation at a favourable applied potential (-1.2 V versus Fc
) and overall thermodynamic efficiency. Certain intermediates of the N
RR cycle would be otherwise unreactive via uncoupled electron transfer or proton transfer steps. Structurally diverse complexes of several metals (W, Mo, Os, Fe) also mediate N
RR electrocatalysis at the same potential in the presence of the mediator, pointing to the generality of this tandem approach.
Metallocenes, including their permethylated variants, are extremely important in organometallic chemistry. In particular, many are synthetically useful either as oxidants (e.g., Cp2Fe+) or as ...reductants (e.g., Cp2Co, Cp*2Co, and Cp*2Cr). The latter have proven to be useful reagents in the reductive protonation of small-molecule substrates, including N2. As such, understanding the behavior of these metallocenes in the presence of acids is paramount. In the present study, we undertake the rigorous characterization of the protonation products of Cp*2Co using pulse electron paramagnetic resonance (EPR) techniques at low temperature. We provide unequivocal evidence for the formation of the ring-protonated isomers Cp*(exo/endo-η4-C5Me5H)Co+. Variable temperature Q-band (34 GHz) pulse EPR spectroscopy, in conjunction with density functional theory (DFT) predictions, are key to reliably assigning the Cp*(exo/endo-η4-C5Me5H)Co+ species. We also demonstrate that exo-protonation selectivity can be favored by using a bulkier acid and suggest this species is thus likely a relevant intermediate during catalytic nitrogen fixation given the bulky anilinium acids employed. Of further interest, we provide physical data to experimentally assess the C–H bond dissociation free energy (BDFEC–H) for Cp*(exo-η4-C5Me5H)Co+. These experimental data support our prior DFT predictions of an exceptionally weak C–H bond (<29 kcal mol–1), making this system among the most reactive (with respect to C–H bond strength) to be thoroughly characterized. These data also point to the propensity of Cp*(exo-η4-C5Me5H)Co to mediate hydride (H–) transfer. Our findings are not limited to the present protonated metallocene system. Accordingly, we outline an approach to rationalizing the reactivity of arene-protonated metal species, using decamethylnickelocene as an additional example.
New electrochemical ammonia (NH3) synthesis technologies are of interest as a complementary route to the Haber-Bosch process for distributed fertilizer generation, and towards exploiting ammonia as a ...zero-carbon fuel produced via renewably sourced electricity1. Apropos of these goals is a surge of fundamental research targeting heterogeneous materials as electrocatalysts for the nitrogen reduction reaction (N2RR)2. These systems generally suffer from poor stability and NH3 selectivity; the hydrogen evolution reaction (HER) outcompetes N2RR3. Molecular catalyst systems can be exquisitely tuned and offer an alternative strategy4, but progress has been thwarted by the same selectivity issue; HER dominates. Here we describe a tandem catalysis strategy that offers a solution to this puzzle. A molecular complex that can mediate an N2 reduction cycle is partnered with a co-catalyst that interfaces the electrode and an acid to mediate proton-coupled electron transfer steps, facilitating N-H bond formation at a favourable applied potential (-1.2 V versus Fc+/0) and overall thermodynamic efficiency. Certain intermediates of the N2RR cycle would be otherwise unreactive via uncoupled electron transfer or proton transfer steps. Structurally diverse complexes of several metals (W, Mo, Os, Fe) also mediate N2RR electrocatalysis at the same potential in the presence of the mediator, pointing to the generality of this tandem approach.
Nitrogen (N2) fixation to produce bio‐available ammonia (NH3) is essential to all life but is a challenging transformation to catalyze owing to the chemical inertness of N2. Transition metals can, ...however, bind N2 and activate it for functionalization. Significant opportunities remain in developing robust and efficient transition metal catalysts for the N2 reduction reaction (N2RR). One opportunity to target in catalyst design concerns the stabilization of transition metal diazenido species (M‐NNH) that result from the first N2 functionalization step. Well‐characterized M‐NNH species remain very rare, likely a consequence of their low N–H bond dissociation free energies (BDFEs). In this essay, we discuss the relationship between the BDFEN–H of a given M‐NNH species to the observed overpotential and selectivity for N2RR catalysis with that catalyst system. We note that developing strategies to either increase the N–H BDFEs of M‐NNH species, or to avoid M‐NNH intermediates altogether, are potential routes to improved N2RR efficiency.
The reduction of N2 to NH3 (N2RR) is a globally significant reaction that is challenging due to the inertness of N2. Transition metals can activate N2 and mediate catalytic N2RR, but challenges remain with respect to catalytic efficiency in terms of overpotential and selectivity. We discuss the role of the N–H bond dissociation free energy (BDFE) of metal diazenidos (M‐NNH), the first intermediates of N2RR, in determining N2RR efficiency.
Accumulation of filamentous aggregates of tau protein in the brain is a pathological hallmark of Alzheimer's disease (AD) and many other neurodegenerative tauopathies. The filaments adopt ...disease-specific cross-β amyloid conformations that self-propagate and are implicated in neuronal loss. Development of molecular diagnostics and therapeutics is of critical importance. However, mechanisms of small molecule binding to the amyloid core is poorly understood. We used cryo-electron microscopy to determine a 2.7 Å structure of AD patient-derived tau paired-helical filaments bound to the PET ligand GTP-1. The compound is bound stoichiometrically at a single site along an exposed cleft of each protofilament in a stacked arrangement matching the fibril symmetry. Multiscale modeling reveals pi-pi aromatic interactions that pair favorably with the small molecule-protein contacts, supporting high specificity and affinity for the AD tau conformation. This binding mode offers critical insight into designing compounds to target different amyloid folds found across neurodegenerative diseases.
Substrate selectivity in reductive multielectron/proton catalysis with small molecules such as N2, CO2, and O2 is a major challenge for catalyst design, especially where the competing hydrogen ...evolution reaction (HER) is thermodynamically and kinetically competent. In this study, we investigate how the selectivity of a tris(phosphine)borane iron(I) catalyst, P3 BFe+, for catalyzing the nitrogen reduction reaction (N2RR, N2-to-NH3 conversion) versus HER changes as a function of acid pK a. We find that there is a strong correlation between pK a and N2RR efficiency. Stoichiometric studies indicate that the anilinium triflate acids employed are only compatible with the formation of early stage intermediates of N2 reduction (e.g., Fe(NNH) or Fe(NNH2)) in the presence of the metallocene reductant Cp*2Co. This suggests that the interaction of acid and reductant is playing a critical role in N–H bond-forming reactions. DFT studies identify a protonated metallocene species as a strong PCET donor and suggest that it should be capable of forming the early stage N–H bonds critical for N2RR. Furthermore, DFT studies also suggest that the observed pK a effect on N2RR efficiency is attributable to the rate and thermodynamics of Cp*2Co protonation by the different anilinium acids. Inclusion of Cp*2Co+ as a cocatalyst in controlled potential electrolysis experiments leads to improved yields of NH3. The data presented provide what is to our knowledge the first unambiguous demonstration of electrocatalytic nitrogen fixation by a molecular catalyst (up to 6.7 equiv of NH3 per Fe at −2.1 V vs Fc+/0).
We have recently reported on several Fe catalysts for N2-to-NH3 conversion that operate at low temperature (−78 °C) and atmospheric pressure while relying on a very strong reductant (KC8) and acid ...(H(OEt2)2BArF 4). Here we show that our original catalyst system, P3 BFe, achieves both significantly improved efficiency for NH3 formation (up to 72% for e– delivery) and a comparatively high turnover number for a synthetic molecular Fe catalyst (84 equiv of NH3 per Fe site), when employing a significantly weaker combination of reductant (Cp*2Co) and acid (Ph2NH2OTf or PhNH3OTf). Relative to the previously reported catalysis, freeze-quench Mössbauer spectroscopy under turnover conditions suggests a change in the rate of key elementary steps; formation of a previously characterized off-path borohydrido–hydrido resting state is also suppressed. Theoretical and experimental studies are presented that highlight the possibility of protonated metallocenes as discrete PCET reagents under the present (and related) catalytic conditions, offering a plausible rationale for the increased efficiency at reduced driving force of this Fe catalyst system.
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