Research Network for Metals in Medicine

 

 

Dr Stephen Best

BSc(Hons), PhD(Melb)

Position: Senior lecturer in Chemistry

Affiliation: School of Chemistry, University of Melbourne

Postal Address:
School of Chemistry
The University of Melbourne
Victoria 3010
AUSTRALIA

Phone:
Fax:
Email: spbest@unimelb.edu.au
Webpage: http://www.chemistry.unimelb.edu.au/staff/spbest/research/index.html

Research Profile

The change in reactivity of transition metal complexes accompanying a change in redox state is a key distinguishing characteristic of the d-block elements. It is this characteristic that is pivotal to their remarkable ability to act as catalysts for an extraordinary range of reactions and explains the high incidence of transition metal compounds / clusters at the active sites of many enzymes.

In the broadest sense our work is driven by a desire to better understand the interplay between structural and electronic interactions that leads to the changes in structure, reactions and reactivity of metal complexes with a change in redox state. In some cases we take our inspiration from the metal complexes revealed by structural characterisation of metalloproteins but in others the focus is clearly on abiological systems.

An important strategy that we have pursued in recent years has been to develop techniques that permit spectroscopic examination of reactive electrogenerated species particularly using techniques such as infrared or UV-visible spectroscopy, an area of research known as spectroelectrochemistry (SEC).

Since our interests include the activation of gaseous species such as H2, CO, CO2, C2H2 etc. it has been necessary to develop techniques that permit our SEC experiments to be carried out at moderate gas pressures (0.1 to 1.o MPa). This provides a means of controlling the concentration of those species in our experiments and permits the systematic study of the coordination chemistry of gaseous molecules with metal complexes and clusters over a range of redox states.

Iron sulfur clusters are found at the active sites of numerous enzymes where they commonly facilitate electron transfer and substrate transformations. Processes involving assembly, rearrangement, degradation and ligand substitution are often triggered by a change in redox state. In addition to the more conventional spectroscopic techniques (IR, UV-Vis, EPR) used in these studies we have recently developed approaches that permit the extraction of structural information from transiently stable electrogenerated complexes using XAFS techniques.
The nitrogenase enzyme catalyses the reduction of N2 to NH3 accompanied by reduction of protons to H2. The enzyme consists of Fe and MoFe component proteins which can be purified separately. The MoFe protein contains two types of metal-sulfur clusters, the P-clusters, and the Fe, Mo cofactor known as FeMoco, believed to be the site of substrate binding and activation. In collaboration with Prof. Chris Pickett (John Innes Centre, UK) we have examined the redox-state dependence of substrate binding to protein-free FeMoco.

Although the structure of FeMoco within crystalline resting-state nitrogenase was first determined in 1992, the sites of substrate and inhibitor coordination are still poorly understood. We have employed a combination of electrochemical and IR spectroscopic techniques to gain insight into the nature of small molecule interactions with isolated cofactor.
The recent elucidation of the structure of the all-iron hydrogenase enzymes has lead to renewed interest in classical binuclear diiron compounds both as models of the H-cluster and as proton reduction catalysts. The reduction chemistry of these compounds is complex, but may be brought under a level of control using p(CO).


Selected Publications

  1. Pickett CJ, Best SP, Vincent K et al, Chem. Commun. 1999, 1019.
  2. Best SP, Borg S, Pickett CJ et al, Chem. Commun. 1999, 2285.
  3. Tregenna-Piggott PLW, Best SP et al, Solid State Chemistry, 1999, 145, 460.
  4. Bruce MI, Best SP et al, J. Am. Chem. Soc. 2000, 122, 194.
  5. Bondin MI, Foran G and Best SP, Aust. J. Chem. 2001, 54, 705.
  6. Razavet M, Borg SJ, George SJ, Best SP, Fairhurst SA and Pickett CJ, Chem. Commun. 2002, 700.
  7. Borg SJ and Best SP, J Electroanal. Chem., 2002, in the press.
  8. Pickett CJ, Vincent KA, Best SP et al, Chemistry, 2002, in the press.