Skip to content Skip to navigation

New Progress in Structural Mimicking of the Nitrogenase FeMo Cofactor

New Progress in Structural Mimicking of the Nitrogenase FeMo Cofactor

Prof. Xu-Dong Chen’s research group in School of Chemistry and Materials Science at Nanjing Normal University (http://schools.njnu.edu.cn/chem/person/xudong-chen) has made significant progress in synthetic mimicking of the nitrogenase FeMo cofactor. In collaboration with Prof. Richard H. Holm at Harvard University, researchers in the Chen group have developed a core ligand metathesis strategy and successfully incorporated light atoms into synthetic analogues of the cofactor. The paper entitled “Ligand metathesis as rational strategy for the synthesis of cubane-type heteroleptic iron–sulfur clusters relevant to the FeMo cofactor” has been published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on April 13, 2018 (https://doi.org/10.1073/pnas.1801025115). A commentary entitled “Incorporating light atoms into synthetic analogues of FeMoco” addressing the importance of this work has also been published in PNAS on April 30, 2018 (https://doi.org/10.1073/pnas.1805700115).

Molybdenum-dependent nitrogenases catalyze the transformation of dinitrogen into ammonia under ambient conditions. The biosynthesis and mechanism of action of this enzyme are problems of prominent significance in metallobiochemistry. Because the active centers of the enzyme (FeMo cofactor) 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.

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. Collaborating with professor R. H. Holm, the Chen group has developed a synthetic approach of core ligand metathesis based on the design and synthesis of unprecedented incomplete ([(Tp*)WFe2S3Q3]) and complete ([(Tp*)WFe3S3Q4]2−) cubane-type clusters containing bridging halide (Q = halide). The approach provides a pathway for constructing heterometal heteroleptic Fe–S clusters of presumed relevance to the active site of the FeMo cofactor. Based on cubane-type stereochemistry, clusters have been prepared allowing alterations in structure and ligand binding, and inclusion of a light core atom. These clusters are achieved by template-assisted assembly in the presence of sodium benzophenone ketyl reductant through the rational control of 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. 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 the first close mimic of the [MoFe3S3C] fragment in the FeMo cofactor. Superposition of them and comparison of metric information disclose a clear structural relationship [Tp* = tris(3,5-dimethyl-1-pyrazolyl)hydroborate(1−)]. Further studies are underway.