Hydrogenase cluster biosynthesis: organometallic chemistry nature's way.

It has been over a decade now since it was revealed that the metal containing active sites of hydrogenases possess carbonyl and cyanide ligands bound to iron. The presence of these ligands in hydrogenases came as a surprise and to-date these ligands have not been observed to be associated with any other enzymatic metallocenter. The elucidation of the structures of these unique metalloenzymes and their associated metal clusters created opportunity for a number of different lines of research. For synthetic chemists, the structures of hydrogenase active sites have provided attractive targets for syntheses that advance our understanding of the electronic structure and reactivity of these unique enzyme active sites. These efforts contribute to the synthesis of first row transition metal catalysts for hydrogen oxidation and hydrogen production that could have significant impacts on alternative and renewable energy solutions. Although effective synthetic approaches have been identified to generate models with a high degree of similarity to these active sites, the details of how these metal clusters are synthesized biochemically have not been resolved. Since hydrogen metabolism is presumed to be an early feature in the energetics of life and hydrogen metabolizing organisms can be traced very early in molecular phylogeny, the metal clusters at hydrogenase active sites are presumed to be among the earliest of known co-factors. Comparison of mineral based precursors and synthetic cluster analog chemistry to what is observed in contemporary biological systems may shed light on how proto-metabolically relevant catalysts first arose prebiotically by the processes of adoption of pre-existing functionality and ligand assisted catalysis.