Molybdenum-dependent nitrogenases catalyze the transformation of dinitrogen into ammonia under ambient conditions. The active site (FeMo cofactor) is the structurally and electronically complex weak-field metal cluster [MoFe₇S₉C] built of Fe₄S₃ and MoFe₃S₃C portions connected by three sulfur bridges and containing an interstitial carbon atom centered in an Fe₆ trigonal prism. Chemical synthesis of this cluster is a major challenge in biomimetic inorganic chemistry. One synthetic approach of core ligand metathesis has been developed based on the design and synthesis of unprecedented incomplete ([(Tp*)WFe₂S₃Q₃]⁻) and complete ([(Tp*)WFe₃S₃Q₄]²⁻) cubane-type clusters containing bridging halide (Q = halide). These clusters are achieved by template-assisted assembly in the presence of sodium benzophenone ketyl reductant; products are controlled by reaction stoichiometry. Incomplete cubane clusters are subject to a variety of metathesis reactions resulting in substitution of a μ₂-bridging ligand with other bridges such as N₃⁻, MeO⁻, and EtS⁻. Reactions of complete cubanes with Me₃SiN₃ and S₈ undergo a redox metathesis process and lead to core ligand displacement and formation of [(Tp*)WFe₃S₃(μ₃-Q)Cl₃]⁻ (Q = Me₃SiN²⁻, S²⁻). This work affords entry to a wide variety of heteroleptic clusters derivable from incomplete and complete cubanes; examples are provided. Among these is the cluster [(Tp*)WFe₃S₃(μ₃-NSiMe₃)Cl₃]⁻, one of the very few instances of a synthetic Fe–S cluster containing a light atom (C, N, O) in the core, which constitutes a close mimic of the [MoFe₃S₃C] fragment in FeMo cofactor. Superposition of them and comparison of metric information disclose a clear structural relationship [Tp* = tris(3,5-dimethyl-1-pyrazolyl)hydroborate(1−)]. Significance The biosynthesis and mechanism of action of nitrogenase, an enzyme that converts dinitrogen to ammonia under ambient conditions, are problems of prominent significance in metallobiochemistry. Because the active centers of the enzyme are metal–ligand clusters, it is feasible that they are attainable by synthesis and as such are primary goals in the field of biomimetic inorganic chemistry. Here we present a ligand metathesis strategy utilizing the periodic near-identity of molybdenum and tungsten when incorporated into analogous compounds. The approach provides a pathway for constructing heterometal heteroleptic Fe–S clusters of presumed relevance to the active site. Based on cubane-type stereochemistry, clusters have been prepared allowing alterations in structure and ligand binding, and inclusion of a light core atom.

The FeMo cofactor (FeMoco), the key active site in the Mo-based nitrogenase, is one of the most complicated metalloenzyme molecules. Synthesis of the FeMoco model cluster ([MoFe ₇ S ₉ C]) is essential to understanding its function in dinitrogen binding, activation, and conversion. However, the complex framework of the FeMoco cluster, which features a unique trigonal prismatic [Fe ₆ C] moiety comprising a µ ₆ -bridging carbide, has made the synthesis of the cluster a persistent challenge. In this work, two analogous mimics of FeMoco have been synthesized, using a cluster-coupling synthetic strategy facilitated by the fabrication of unsaturated ligand/metal coordination. The incorporation of a µ ₆ -X (X = C ⁴⁻ or N ³⁻ ) to construct the characteristic triangular prismatic [Fe ₆ ( µ ₆ -X)] moiety, replicating that in FeMoco, has been achieved synthetically. The two mimics have similar key structural parameters to FeMoco in natural nitrogenase, but differ from the FeMoco structure in two major aspects: the µ ₂ -bridging ligands and the metal atoms capping the [Fe ₆ S ₉ C] cores (Mo/Fe in FeMoco vs. Mo/Mo or W/W in the synthetic models). Quantum chemical studies indicate that the electronic ground states of these clusters resemble those observed for FeMoco, with maximized antiferromagnetic coupling among the iron centers. A future systematic study on the physical and chemical properties of a family of mimics with programmed variations of key structural elements can provide a valuable comparison and facilitate a better understanding of the structure and function of FeMoco.

Structural mimicking of the nitrogenase FeMo cofactor has long been a challenge in synthetic inorganic chemistry and bioinorganic chemistry. This already very tough task had become even harder after the discovery of an interstitial light atom, which was later evidenced to be carbide. From a synthetic point of view, to introduce such a 2p atom into the core of a Fe–S cluster would have to overcome the coordination competition from overwhelming sulfide ligands. Recently, we have reported a controlled synthetic strategy named redox metathesis based on template-assisted structure design, and have successfully synthesized a couple of nitride-incorporated edge-bridged double cubane (N-EBDC) W–Fe–S clusters. In this work, we have systematically studied the terminal ligand substitutions of heteroleptic N-EBDC clusters, utilizing ethanethiolate, thiophenolate, p-thiocresolate, azide, and methoxide to replace the terminally bound chloride ligands. Structural analysis of this family of N-EBDC clusters reveals that different terminal ligands affect the fine structures of the cluster cores at different levels. Further studies by cyclic voltammetry indicate that these N-EBDC clusters with distinct terminal ligands exhibit different redox behaviors, furnishing in-depth information on the electronic structure of these clusters potentially related to their reactivity. This study provided useful information for the investigation of nitrogenase related Fe–S clusters toward structural and functional mimicking of the nitrogenase FeMo cofactor.