Incorporating light atoms into synthetic analogues of FeMoco

Nitrogen is an essential element for all life on Earth. However, the elemental form of dinitrogen (N2) is typically inert, and must be converted to the more reactive and biologically accessible ammonia (NH3) before incorporation into proteins, nucleic acids, and other biomolecules. In nature, the only enzymes capable of the multielectron reduction of N2 to NH3 are nitrogenases, whose complexity has captured the imagination of biochemists (1), synthetic chemists (2), and spectroscopists (3) alike. Their active sites are iron–sulfur clusters that are produced through elaborate biosynthetic pathways (4). One special aspect of the nitrogenase active-site clusters is the presence of molybdenum or vanadium heteroatoms in addition to iron: the cofactors are described as the iron–molybdenum cofactor (FeMoco) or the iron–vanadium cofactor (FeVco). Because of the unusual shape of these clusters, and the desire to systematically understand the influence of the Mo/V atom on an iron–sulfur cluster, chemists have long striven to synthesize simpler analogs (5). These synthetic analogs are influential because they can demonstrate feasible mechanistic steps and can enable correlation of specific structural features with spectroscopic signatures. In a relevant example, synthetic chemists have prepared eight-metal clusters with topological similarity to the FeMoco and FeVco (6⇓⇓–9). However, a newer challenge for synthetic chemists is presented by the light atom in the center of the FeMoco and FeVco, which has been identified as a carbide (C4-) that has no precedent in biology (Fig. 1) (10⇓–12). The discovery of an interstitial carbon in the cofactors raises fundamental questions about the bonding, reactivity, and role of a central carbide within an iron–sulfur cluster, and about the … [↵][1]1To whom correspondence should be addressed. Email: patrick.holland{at}yale.edu. [1]: #xref-corresp-1-1