Faculty of Science School of Chemistry

Tony Wedd

Professor of Chemistry

CONTACT DETAILS:

Address: School of Chemistry, Bio 21 Institute, University of Melbourne, Parkville, VIC 3010, Australia

Room: Bio 21 Inst. 431

Email: agw@unimelb.edu.au

For more information, please visit the Wedd Group

 

Teaching responsibilities

 

 

Field of expertise

The research focuses on the chemistry of the essential trace metals of biology and on metal clusters in artificial photosynthesis (ways to harvest the energy of the sun as new, green sources of energy).

Poly-oxo anion chemistry

These anions are soluble clusters of metal and oxygen atoms whose symmetric structures are related to the insoluble metal oxides (eg, Figure 1).

As they are cheap, robust and non-toxic, they have potential as new green catalysts. We are studying two aspects:

  1. It is now possible to study catalytic cycles in the gas phase by mass spectrometry to obtain new molecular insights.[1,2]
  2. The clusters are highly photo-active and redox-active (can be oxidised and reduced). These properties have led to very promising and simple photo-catalysts which use light as an energy source (including ones which oxidize H2O to O2: "artificial photosynthesis".[3] We have recently combined the anions with dye cations to allow harvesting of visible light.[4]
Fig. 1: The [H2W12O40]6- anion
Figure 1: The [H2W12O40]6- anion

 

Biological inorganic chemistry

The trace metals are essential to life for enzymes but are highly toxic in excess. A balance between deficiency and toxic excess must be maintained. The secrets of their catalytic and structural roles are under intensive scrutiny.

Acquisition of the metals is mediated by molecular membrane pumps and by transport proteins which take the metal to its destinations in biological cells. Figure 2 shows a simplified representation of transport of copper in mammalian cells. Defects in copper metabolism cause Menkes and Wilson diseases in humans and is a component of certain neurodegenerative diseases (Alzheimer, Creutzfeldt-Jakob, mad cow).

Fig. 2: Copper transport and distribution in a mammalian liver cell
Figure 2: Copper transport and distribution in a mammalian liver cell

 

The molecular pump Ctr1 (Copper Transporter no. 1 ) is primarily responsible for import of copper into human cells. It appears to interact with the transport proteins (chaperones) via a beautiful Cu4S6 cluster (Figure 3).[5] In addition, the platinum cancer drug cis-platin enters certain cells via the Ctr1 pump. Interactions of cis-platin with the copper proteins appears to be a major cause of loss of drug and side effects. We are studying the pumps and chaperones and their interactions with cis-platin.

Certain bacteria have developed the unusual ability to survive in environments with millimolar concentrations of copper (>1,000 times higher than normal nutrient levels). They have evolved clusters of genes which are induced by copper and whose protein products combine to export excess copper (Figure 4). We have studied the properties of the protein PcoC (CopC) and shown that it has the unique ability to bind copper in either of its oxidation states CuI and Cu(II) (Figure 5).[6] In addition, the oxidase enzyme PcoA can oxidise CuI bound to PcoC catalytically to the less toxic Cu(II) form.[7] This can then be pumped out of the cell.

The proteins are generated via molecular genetics and then purified. The molecular probes needed are provided by techniques such as NMR, ESR, MS, fluorescence, X-ray crystallography, electro-chemistry and quantitative HPLC.

New projects include:

  1. design and synthesis of new chromophoric ligands to act as quantitative probes of bio-metals, both in vivo and in vitro;
  2. transport of nutrient metals in normal and in hyper-accumulating plants.[8]
  3. Zinc and copper transporters in the simple plant Arabidopsis thaliana .
  4. Cell-free expression of membrane proteins (such as CopB, D, R of Figure 4).

 

Fig. 3: The Cu6S6 cluster (Cu atoms are pink)
  
Fig. 5: Copper chaperone protein PcoC
Figure 3: The Cu6S6 cluster (Cu atoms are pink)
 
Fig. 4: Resistance proteins expressed to periplasm in E. coli cells
Figure 4: Resistance proteins expressed to periplasm in E. coli cells
  
Figure 5: Copper chaperone protein PcoC
(a) Cu atoms bind at each end;
(b) Detail of CuII binding site.

 

Selected Publications:
  1. T. Waters, G. N. Khairallah , S. A. S. Y. Wimala, Y. C. Ang, R. A. J. O'Hair and Anthony G. Wedd, J. Chem. Soc. Chem. Commun. 2006, 4503-4505.
  2. T. Waters, A. G. Wedd and R. A. J. O'Hair, Eur. J. Chem. 2007, 13, 8818-8829.
  3. N. Fay, V. M. Hultgren, A. G. Wedd, T. E. Keyes, D. Leane and A. M. Bond, J.Chem. Soc. Dalton Transactions 2006, 4218-4227.
  4. J. Xie, B. F. Abrahams and A. G. Wedd, Chem. Commun. 2007, accepted for publication.
  5. Z. Xiao, F. Loughlin, G. N. George, G. Howlett and A.G. Wedd, J. Amer. Chem. Soc. 2004, 126, 3801-3890.
  6. L. Zhang, M. Koay, M. J. Maher,   Z. Xiao and A. G. Wedd, J. Am. Chem. Soc. 2006, 128, 5834-5850.
  7. K. Y. Djoko, Z. Xiao and A. G. Wedd, J. Am. Chem. Soc. 2007, in press.
  8. D. Callahan, A. Baker, S. D. Kolev, A. G. Wedd, J. Biol. Inorg. Chem., 2006, 11, 2-12.

 
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