Nitrogenases redox activation

These studies of protein-bound heterometallic cubanes have amply demonstrated that the heterometal site is redox active and able to bind small molecules. Although they have yet to be identified as intrinsic components of any protein or enzyme (except as part of the nitrogenase FeMo cofactor cluster (254)), they are clearly attractive candidates for the active sites of redox enzymes. 

Molybdenum is found in the active site of nitrogenase as part of a multinuclear cluster with iron (the so-called M-cluster), but in all other enzymes it comprises a mononuclear center (Hille, 1996 Kisker et al., 1997a). The distinguishing characteristic of this latter group of enzymes is that, while other redox-active centers are often present, the molybdenum center itself possesses only a single equivalent of the transition metal. This large and diverse group of enzymes is the subject of the present account. 

At the same time, this redox lability makes Mo well suited as a cofactor in enzymes that catalyze redox reactions. An example is the prominence of Mo in nitrogen fixation. This prokaryotic metabolism, the dominant pathway for conversion of atmospheric Nj to biologically-useful NH, utilizes Mo (along with Fe) in the active site of the nitrogenase enzyme that catalyzes Nj reduction. Alternative nitrogenases that do not incorporate Mo have been identified, but are markedly less efficient (Miller and Eady 1988 Eady 1996). 

Transition metal sulfide units occur in minerals in nature and play an important role in the catalytic activity of enzymes such as hydrogenase and nitrogenase. Industrial processes use transition metal sulfides in hydroprocessing catalysis. Both the metal and the sulfur sites in these compounds can undergo redox reactions which are an important part of their reactivity. Thus, the electronic situation of the ReS4 anion and related complexes is of considerable interest and has been evaluated applying quantum chemical methods. 

Thus, the hybrid cluster is a putative iron-sulfur redox catalyst. It is, however, a very uncommon cluster (perhaps only comparable to the nitrogenase active site) in two aspects (1) it is a hybrid cluster i.e., it contains intrinsic building blocks that are distinctly strange to iron-sulfur clusters and (2) it can exist in more than two (in fact, four [63]) oxidation states. 

Biological N2 fixation (1), i.e., the reduction of N2 to NH3 catalyzed by FeMo, FeV, or FeFe nitrogenases, is one of the fundamental synthetic processes of nature (2-4). In spite of intense efforts over the last decades, its molecular mechanism is poorly understood, in particular because the pivotal chemical question has remained unanswered how do nitrogenases achieve to activate and convert the inert N2 molecule to ammonia under ambient conditions and mild redox potentials. 

---