Faculty of Science School of Chemistry

Paul Donnelly

Lecturer

CONTACT DETAILS:

Address: Bio21 Institute, School of Chemistry, University of Melbourne, Parkville, VIC, 3010 Australia

Room: Bio21 Inst., 506

Email: pauld@unimelb.edu.au

 

Teaching responsibilities

 

Field of expertise

Metals in Medicine and Biology

Research in the Donnelly Group broadly focuses on the application of synthetic inorganic/organic chemistry to biology and materials science. In particular, I am interested in the application of coordination chemistry to metal-based drugs and the study of metal ions in biological systems.

One of the principle objectives is the development of new radiopharmaceuticals for analysis and diagnosis. This involves organic synthesis of specifically designed ligands (Figure 1) to complex certain metal radionuclides and allow selective delivery of radiation to disease sites. Our current projects focus on copper, rhenium and technetium systems. This radiation can be used for either diagnostic imaging analysis or therapy of the disease. Further selectivity can be achieved by tethering biologically active molecules, such as site-specific peptides to the complexes.

Another major project focuses on the design, synthesis and characterisation of copper and zinc complexes for the treatment of Alzheimer's disease. Our work in collaboration with Drs Barnham and White (Dept of Pathology) attempts to better understand molecular aspects of the condition.

We also probe the mechanism of action of metal-based drugs by a variety of techniques. One approach is to synthesise fluorescent labelled drugs to investigate their uptake and intracellular distribution in cancer cells using fluorescent microscopy (Figure 2). We are also investigating the interaction of copper complexes with proteins that occur inside cells that are specifically designed to traffic metal ions to certain organelles where the copper is incorporated into cuproenzymes.

Our interest in Platinum anti-cancer drugs includes the design and synthesis of new platinum complexes, and the interaction of known platinum drugs with proteins implicated in their uptake into cancer cells.

Our multidisciplinary research involves chemical synthesis and the application of a wide range of analytical techniques including: multinuclear NMR, mass spectrometry, electronic and fluorescent spectroscopy, EPR, electrochemical techniques and X-ray crystallography.

The research group is based in new 'state of art' laboratories in the $100 million Bio21 Institute of Molecular Science and Biotechnology building that opened in 2005. This exciting development provides state-of-the-art facilities for researchers in a dynamic interdisciplinary environment.

Collaborations include: Prof. Wedd, Dr. Xiao, Dr. Williams (Chemistry); Dr. Kevin Barnham, Dr. Tony White (Pathology); Prof. Jon Dilworth (Oxford, UK) as well as links with industry and Austin Hospital

For further information visit the Donnelly group web page.

 

fig 1, Representations of structures of two new copper complexes designed as radiopharmaceuticals
Figure 1. Representations of structures of two new copper complexes designed as radiopharmaceuticals. See references 2 and 4.
fig 2, Fluorescent image of a fluorescent labeled metal complex in a cancer cell
Figure 2. Confocal microscopy image of a fluorescent labeled metal complex in a cancer cell.

 

Selected Publications:
  1. Ma, M. T.; Karas, J. A.; White, J. M.; Scanlon, D.; Donnelly, P. S., A new bifunctional chelator for copper radiopharmaceuticals: a cage amine ligand with a carboxylate functional group for conjugation to peptides. Chem Commun, 2009, 3237.
  2. Crouch, P. J.; Hung, L. W.; Adlard, P. A.; Cortes, M.; Lal, V.; Filiz, G.; Perez, K. A.; Nurjono, M.; Caragounis, A.; Du, T.; Laughton, K.; Volitakis, I.; Bush, A. I.; Li, Q.-X.; Masters, C. L.; Cappai, R.; Cherny, R. A.; Donnelly, P. S.; White, A. R.; Barnham, K. J., Increasing Cu bioavailability inhibits Abeta oligomers and tau phosphorylation. Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 381.
  3. Donnelly, P. S.; Zanatta, S. D.; Zammit, S. C.; White, J. M.; Williams, S. J., 'Click' cycloaddition catalysts: copper(I) and copper(II) tris(triazolylmethyl)amine complexes. Chem. Commun., 2008, 2459.
  4. Donnelly, P. S.; Caragounis, A.; Du, T.; Laughton, K. M.; Volitakis, I.; Cherny, R. A.; Sharples, R. A.; Hill, A. F.; Li, Q.-X.; Masters, C. L.; Barnham, K. J.; White, A. R., Selective Intracellular Release of Copper and Zinc Ions from Bis(thiosemicarbazonato) Complexes Reduces Levels of Alzheimer Disease Amyloid-beta Peptide. J. Biol. Chem., 2008, 283, 4568.
  5. Donnelly, P. S.; Xiao, Z and Wedd, A. G., Copper and Alzheimer's disease. Curr. Opin. Chem. Biol , 2007, 11, 128.
  6. Cowley, A. R.; Dilworth, J. R.; Donnelly, P. S.; White, J. M., Copper Complexes of Thiosemicarbazone-Pyridylhydrazine (THYNIC) Hybrid Ligands: A New Versatile Potential Bifunctional Chelator for Copper Radiopharmaceuticals. Inorg. Chem., 2006, 45, 496.
  7. Cowley, A. R. ; Dilworth, J. R; Donnelly, P. S.; Heslop, J. M. and Ratcliffe, S. J. Dalton Trans., 2007, 209.
  8. Cowley, A. R.; Davis, J.; Dilworth, J. R.; Donnelly, P. S.; Dobson, R.; Nightingale, A.; Peach, J. M.; Shore, B.; Kerr, D. and Seymour, L., Chem. Commun., 2005, 845.
 
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