Insight into the Iron–Molybdenum Cofactor of Nitrogenase from Synthetic Iron Complexes with Sulfur, Carbon, and Hydride Ligands

Abstract

Nitrogenase enzymes are used by microorganisms for converting atmospheric N2 to ammonia, which provides an essential source of N atoms for higher organisms. The active site of the molybdenum-dependent nitrogenase is the unique carbide-containing iron-sulfur cluster called the iron-molybdenum cofactor (FeMoco). On the FeMoco, N2 binding is suggested to occur at one or more iron atoms, but the structures of the catalytic intermediates are not clear. In order to establish the feasibility of different potential mechanistic steps during biological N2 reduction, chemists have prepared iron complexes that mimic various structural aspects of the iron sites in FeMoco. This reductionist approach gives mechanistic insight, and also uncovers fundamental principles that could be used more broadly for small molecule activation. Here, we review recent results and highlight directions for future research. In one direction, synthetic iron complexes have now been shown to bind N2, break the N-N triple bond, and produce ammonia catalytically. Carbon and sulfur based donors have been incorporated into the ligand spheres of Fe-N2 complexes to show how these atoms may influence the structure and reactivity of the FeMoco. Hydrides have been incorporated into synthetic systems, which can bind N2, reduce some nitrogenase substrates, and/or reductively eliminate H2 to generate reduced iron centers. Though some carbide-containing iron clusters are known, none yet have sulfide bridges or high-spin iron atoms like the FeMoco.

High‐Frequency Fe–H Vibrations in a Bridging Hydride Complex Characterized by NRVS and DFT

“…[3] High-spin metal hydrides [4] are rarely isolated, but are likely to be involved in catalysis with weak-field first-row metal environments [5] and as intermediates in nitrogenase catalysis at iron-sulfur clusters. [3, 6] In a species trapped during proton reduction by nitrogenase, Electron-Nuclear Double Resonance (ENDOR) spectroscopy demonstrated the presence of two iron-bound hydrides in the E 4 (“Janus”) intermediate because the species releases two molecules of H 2 to return to the resting E 0 state. [7] The location of these hydrides is not yet known, and may be important for preparing the paramagnetic FeMo cofactor for N 2 binding.…”

Controlled Incorporation of Nitrides into W‐Fe‐S Clusters

“…Most existing iron nitride complexes are either high‐valent (Fe IV and Fe V ) or low‐valent (Fe 0 and Fe I ), such as linear dinuclear iron nitride compounds stabilized by macrocyclic ligands and polynuclear iron carbonyls with interstitial nitrides developed in earlier days, as well as complexes with terminal nitride bound to iron through multiple bond which has attracted considerable recent interest . The FeMo cofactor responsible for dinitrogen activation, however, is apparently a mid‐valent species likely containing Fe II,III in the resting state . Synthetic mid‐valent iron nitride complexes may permit better elucidation of potential ligand behaviour of nitride associated with dinitrogen activation process.…”

Dinitrogen Activation and Functionalization Using β‐Diketiminate Iron Complexes

“…In order to gain insights into its complex structure and unprecedented central carbide, synthetic chemists have attempted to independently synthesize these metalloclusters, but these efforts have so far been unsuccessful. Iron complexes with limited biomimetic features have been successfully synthesized, including various Fe–S clusters, Fe‐carbide complexes, Fe‐N 2 complexes with S‐ or C‐supporting ligands, as well as Fe complexes with bridging hydrides to mimic catalytic intermediates in the nitrogenase cycle …”

“…These options include end‐on binding of N 2 , η 2 coordination, and end‐on and/or side‐on bridging modes. [6b], , In the case of nitrogenase, a diiron site for N 2 coordination and reduction recently has been supported in the vanadium‐iron nitrogenase enzyme by a crystal structure where one of the belt sulfides is displaced from the cluster …”