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Iron–Sulfur Models of Protein Active Sites

  1. David J. Collins,
  2. Hong-Cai Zhou

Published Online: 15 DEC 2011

DOI: 10.1002/9781119951438.eibc0108

Encyclopedia of Inorganic and Bioinorganic Chemistry

Encyclopedia of Inorganic and Bioinorganic Chemistry

How to Cite

Collins, D. J. and Zhou, H.-C. 2011. Iron–Sulfur Models of Protein Active Sites . Encyclopedia of Inorganic and Bioinorganic Chemistry. .

Author Information

  1. Miami University, Oxford, OH, USA

Publication History

  1. Published Online: 15 DEC 2011

This is not the most recent version of the article. View current version (14 JUN 2015)


In pervasiveness of occurrence and multiplicity of function, iron–sulfur clusters rival biological prosthetic groups such as hemes and flavins. The development of iron–sulfur cluster chemistry paralleled the founding and maturation of the field of bioinorganic chemistry. Starting from the first spontaneous self-assembly of the [Fe4S4(SR)4]2− cluster in 1972, and the identification of the protein-bound Fe4S4 in the same year, the study of iron–sulfur models of protein active sites has evolved into a unique field in which synthetic inorganic chemistry now resembles the total synthesis of natural products in organic chemistry. Some of the models had been built before the crystal structure of the protein was determined. Almost all the models successfully replicated the topology and the electronic properties of the protein active sites. In this article, the models will be discussed in the order of their complexity, from single iron rubredoxin models to Fe2S2, Fe3S4, Fe4S4, and Fe8S7 model compounds. In each section, the chemical synthesis of the model compound will be discussed first, followed by structure comparison and contrast, electrochemical properties, and biochemical activities. Since the major function of iron–sulfur proteins is electron transfer, and the oxidation state of the iron atom determines its reactivity, electrochemical and Mössbauer data will be tabulated in detail. Some of the recent developments in site-differentiated, peptide, and all-ferrous Fe4S4 clusters will be reviewed. Recent studies in modeling the topology of the P-cluster of nitrogenase will also be covered. The challenge posed by iron–sulfur proteins has inspired new iron–sulfur cluster chemistry. No other metal–nonmetal combination has produced more structural types than the iron–sulfur system; the majority of them have yet to be found in biological systems. However, the modeling of the P-cluster and the FeMoco center of nitrogenase have posed a daunting challenge to the analog chemists.


  • iron–sulfur;
  • model compounds;
  • rubredoxin;
  • ferredoxin;
  • P-cluster;
  • cubane;
  • cuboidal;
  • peptide model;
  • site-differentiated;
  • electrochemical property;
  • Mössbauer data