Research Network for Metals in Medicine



Dr Ronald Fenton

Met. Cert., BSc(Hons), PhD(Macq)

Position: Lecturer in Chemistry

Affiliation: School of Chemistry, University of Sydney

Postal Address:
School of Chemistry, Building F11
University of Sydney, NSW, 2006

Phone: +61 (2) 9351 2781
Fax: +61 (2) 9351 3329

Research Profile

Platinum(II) complexes: This work, in collaboration with Dr T W Hambley, involves the design and synthesis of novel platinum(II) anti-cancer drugs, the goal being to produce new anti-cancer drugs with properties different to those in current use. Properties such as the solubility and reactivity of the metal complexes can be modulated by the donor atoms (and substituents on these donor atoms) on the coordination sphere. We are developing and testing a number of series of complexes to examine the factors that determine their reactivity. One of the prime requirements for complexes of these types that are used in biological testing is that they are chemically and isomerically pure. We are developing new synthetic methods that enable us to produce platinum(II) complexes in very high yield and purity.

Octahedral metal complexes multidentate ligand systems: The stereochemistry adopted by a multidentate ligand on coordination to an inert octahedral metal ion is determined by the steric constraints imposed by the substituents on the ligand. As well as the topology adopted by the complex the electronic properties and reactivity may also be significantly influenced by the type of substituent used. We are designing and synthesising multidentate ligands and their representative metal complexes to examine the factors that produce stereospecific ligands.

The synthetic use of cobalt(III) complexes: Research into the derivation of cost efficient procedures for the stereoselective synthesis or resolution of chiral organic molecules is of prime commercial interest to the pharmaceutical industry. A major component of that research is the synthesis of peptide-derived chemotherapeutics, necessitating the development of methods for the isolation of a wide variety of optically pure *-amino acids and congeners such as *-hydroxy acids. The use of appropriate chiral octahedral cobalt(III) complexes as substrates to resolve racemic mixtures of organic mixtures or for metal-mediated asymmetric syntheses are important areas of our research, employing both coordination chemistry in conjunction with synthetic organic chemistry.

The characterisation of metal complexes by neutron diffraction: In collaboration with Dr B J Kennedy and Dr B A Hunter, ANSTO - This work is currently focussed on the synthesis and the determination of the structures, by neutron diffraction, of selected metal complex systems such as the metal(II)-complexes displaying cis-trans-isomerisation and of substituted hydroxy apatites.

Selected Publications

  1. The preparation, characterisation, cytotoxicity and mutagenicity of a pair of enantiomeric platinum(II) complexes designed to bind enantioselectively to DNA, K. Vickery, A. M. Bonin, R. R. Fenton, S. O'Meara, P. J. Russell, L. Webster and T. W. Hambley, J. Med. Chem., 36, 3663 (1993).
  2. Stereoisomerism in palladium(II) complexes of a series of chiral bis-picolyl N4 tetradentates, R. R. Fenton, F. S. Stephens, R. S. Vagg and P. A. Williams, Inorg. Chim. Acta, 231, 73 (1995).
  3. Enantiomeric discrimination in ternary cobalt(III) complexes of N,N'-dimethyl-N,N'-di(picolyl)-1S,2S-diaminocyclohexane and *-amino acids; including the crystal structure of the S-prolinato complex, R. R. Fenton, F. S. Stephens, R. S. Vagg, and P. A. Williams, Inorg. Chim. Acta, 236, 109 (1995).
  4. The preparation, DNA binding and in vitro cytotoxicity of a pair of enantiomeric platinum(II) complexes, [(R)- and (S)-aminohexahydroazepine]dichloro-platinum(II). Crystal structure of the (R)-enantiomer, R. R. Fenton, W. J. Easdale, H. M. Er, S. M. O'Mara, M. J. McKeage, P. J. Russell and T. W. Hambley, J. Med. Chem., 40, 1090 (1997)