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

Nature. 2005 Feb 10;433(7026):610-3. doi: 10.1038/nature03298.


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, synthetic assemblies and in silico models--will help guide the design of new materials for hydrogen production or uptake. 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.).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Biomimetic Materials / chemical synthesis*
  • Biomimetic Materials / chemistry*
  • Catalysis
  • Clostridium / enzymology
  • Desulfovibrio desulfuricans / enzymology
  • Electrochemistry
  • Hydrogen / chemistry*
  • Hydrogenase / chemical synthesis*
  • Hydrogenase / chemistry*
  • Iron / chemistry*
  • Iron-Sulfur Proteins / chemical synthesis
  • Iron-Sulfur Proteins / chemistry
  • Models, Molecular
  • Oxidation-Reduction
  • Protons
  • Structure-Activity Relationship
  • Sulfur / chemistry


  • Iron-Sulfur Proteins
  • Protons
  • Sulfur
  • Hydrogen
  • Iron
  • Hydrogenase