Synthesis of the H-cluster framework of iron-only hydrogenase

The metal- sulphur active sites of hydrogenases catalyse hydrogen evolution or uptake at rapid rates. Understanding the structure and function of these active sites - through mechanistic studies of hydrogenases(1 - 4), synthetic assemblies(5 - 12) and in silico models(13 - 15) - will help guide the design of new materials for hydrogen production or uptake(16). Here we report the assembly of the iron- sulphur framework of the active site of iron- only hydrogenase ( the H- cluster), and show that it functions as an electrocatalyst for proton reduction. Through linking of a di- iron subsite to a {4Fe4S} cluster, we achieve the first synthesis of a metallosulphur cluster core involved in small- molecule catalysis. In addition to advancing our understanding of the natural biological system, the availability of an active, free- standing analogue of the H- cluster may enable us to develop useful electrocatalytic materials for application in, for example, reversible hydrogen fuel cells. ( Platinum is currently the preferred electrocatalyst for such applications, but is expensive, limited in availability and, in the long term, unsustainable(17).)