Research Network for Metals in Medicine

 

 

Dr Janice Aldrich-Wright

BAppSc(Hons)(NSWIT), PhD(Macq), MRACI, CChem

Position: Lecturer, Chemistry

Affiliation: University of Western Sydney, School of Science, Food and Horticulture

Postal Address:
School of Science, Food and Horticulture
University of Western Sydney, Campbelltown Campus
Locked Bag 1797
Penrith South DC, NSW 1797
AUSTRALIA

Phone: +61 (02) 4620 3218
Email: j.aldrich-wright@uws.edu.au
Webpage: http://www.uws.edu.au/about/acadorg/cste/ssfh/staff/academicstaff/jaldrich-wright/profile


Research Profile

Dr Aldrich-Wright was awarded the 1994 Cornforth Medal of the Royal Australian Chemical Institute (RACI) for her PhD thesis entitled “Processes in Some Metal Chelate Systems of Biological Interest”. The citation for this award reads: “The medal is awarded annually for the most outstanding PhD thesis submitted in a branch of chemistry, chemical science or chemical technology. The medal is designed to give recognition of outstanding achievement in chemistry and to promote chemical communication.” She has also received a British Council Postgraduate Travelling Scholarship in 1990, a Ramaciotti Fellowship in 1999, and was awarded a Best Poster Award at the RACI National Convention in Adelaide 1995. In addition she has been appointed a Visiting Scientist to the University of Wales, Cardiff, U.K., and the University of British Columbia, Canada in 1989. She has received invitations to speak at national and international conferences and institutions, and she maintains active collaborations with research groups in Warwick, San Diego, Sydney, Canberra and Townsville.

Dr Aldrich-Wright has served as the New South Wales representative for the Inorganic Division of the RACI from 1996 onwards.

Dr Aldrich-Wright is a member of staff in one of Australia’s newest universities. She has begun her academic career in a department lacking most of the major chemical instrumentation available at established universities. In addition she works in a multidisciplinary department that teaches chemical, food and horticultural science. This has meant that there have been relatively few high quality graduates seeking to enrol in a PhD program in chemistry. Despite these setbacks her collaboration with Dr Grant Collins has resulted in frequently cited publications in high quality journals (6 of these in either Inorganic Chemistry, Dalton Transactions or Journal of the American Chemical Society).

Owing largely to her energy and enthusiasm the University of Western Sydney has recently acquired several key pieces of equipment. This includes a 300 MHz NMR spectrometer and 810 circular dichroism spectrometer (both previously unavailable on campus), which were obtained through ARC-RIEF grants. In addition in 2002 the CD/LD spectrometer will be equipped to also measure linear dichroism, making it the only such facility in New South Wales. Acquisition of these pieces of equipment now means that it is possible to further studies on the extensive range of compounds that Dr Aldrich-Wright and her group have prepared over the past 7-8 years. These improvements in facilities and Dr Aldrich-Wright’s strong network of domestic and international collaborators will greatly facilitate a strong increase in research output.

Dr Aldrich-Wright has made several significant contributions to our understanding of metal/DNA interactions. One of her major achievements has been the systematic design and synthesis of numerous metallointercalator complexes with the aim of delineating the relative contributions of different types of non-covalent interactions with DNA. In collaboration with Dr. Grant Collins she has demonstrated by NMR that D-[Ru(phen)2(dpq)]2+,L-[Ru(2,9-phenMe2)2(dpq)]2+ and more recently D-[Ru(2,9-phenMe2)2(dppz)]2+ bind to the oligonucleotide d(GTCGAC)2 by intercalation from the minor groove. These are the first octahedral metal complexes reported to exhibit minor groove intercalation, which is a significant discovery because the differences in binding of these simple molecules must be well understood if sequence selective DNA probes and repair agents are to be ultimately realised.

Another area where she has contributed has been the development of chiral stationary phases for chromatography. These have allowed the simultaneous comparison of the DNA binding affinity of several metal complexes, and can also be used to separate chiral dinuclear metal complexes.

More recently she has, in collaboration with Dr Ron Fenton, discovered a novel group of platinum compounds that show very high levels of activity against a number of cancer cell lines including cisplatin resistant tumour cells. These compounds form the basis of a Patent (PCT/AU02/00167) that differ significantly from current anticancer compounds in their mode of action. A second patent Sequence Selective Compounds (Provisional No. PR905512) has recently been filed for the resulting compounds from the project Synthesis of Sequence Specific Platinum Drugs.



Selected Publications

    Patents
  1. Metal Complexes and Therapeutic uses thereof, R.R. Fenton and J. R. Aldrich-Wright, Australian Provisional Patent, Application Number PR3302, Feb., (2001)
  2. Metal Complexes and Therapeutic uses thereof, R.R. Fenton and J. R. Aldrich-Wright, International Patent, Application Number PCT/AU02/00167, Oct., (2002)
  3. Sequence Selective Compounds J. R. Aldrich-Wright, D. Jaramillo, C. Brodie and W. Howard. Australian Provisional Patent, Application Number PR905512, Oct., (2003)
  4. Refereed Articles and Monographs:

  5. HPLC Separation of Diasteromeric Metal Complexes of the form D, L-[Ru(diimine)2(aminoacidate)]n+. J. Aldrich-Wright, P. Williams, and R. Vagg, Aust. J. Chem., 56 (12), (2003), 1193-1200.
  6. Reactions of Ruthenium Metallointercalators with DNA Studied Using ESI Mass Spectrometry, J. L. Beck, R. Gupta, T. Urathamakul, N. Williamson, M. M. Sheil, J. R. Aldrich-Wright and S. F. Ralph, Chem. Comm., (2003), 626-627.
  7. Evidence for chiral discrimination of Ruthenium(II) polypyridyl complexes by DNA, P. Pellegrini and J. Aldrich-Wright, Dalton Trans., (2003), 176-183.
  8. The Stereospecific Synthesis of L-a-[N,N’-Dimethyl-N,N’-bis(2-picolyl)-diaminocyclohexane(dipyrido[3,2-a:2’,3’-c]-6,7,8,9-tetrahydrophenazine) Ruthenium(II)] Perchlorate and related b isomers, J. Aldrich-Wright, R. Fenton, I. Greguric, P. Williams and T. Hambley, J. Chem. Soc. Dalton Trans, (2002), 4666-4671
  9. Minor Groove Intercalation of D-[Ru(Me2phen)2dppz]2+ to the Hexanucleotide d(GTCGAC)2, A. Greguric, I. D. Greguric, T. W. Hambley, J. Aldrich-Wright and J. G. Collins, J. Chem. Soc., Dalton Trans., (2002), 849-855.
  10. Paper: A Cheap Yet Effective Chiral Stationary Phase for Chromatographic Resolution of Metallo-Supramolecular Helicates. M. J. Hannon, I. Meistermann, C. J. Isaac, C. Blomme, J. Aldrich-Wright and A. Rodger, Chem Commun., (2001), 1078-1079.
  11. The Binding of [(en)Pt(m-dpzm)2Pt(en)]4+ to G/C Rich Regions of DNA, N. J. Wheate, S. M. Cutts, D. R. Phillips, J. Aldrich-Wright and J. G. Collins, J. Inorg. Biochem. 84, (2001), 119-127.
  12. Interaction of [Pt(en)(phen)]2+ and [Pt(en)(phi)]2+ with the Hexanucleotide d(GTCGAC)2: Evidence for Minor Groove Binding, J. G. Collins, R.M. Rixon and J. Aldrich-Wright, Inorg. Chem. (2000), 39, 4377-4378.
  13. Binding of the L andD Enantiomers of [Ru(dmphen)2DPQ]2+ to the Hexanucleotide d(GTCGAC)2, J. G. Collins, J. Aldrich-Wright, I. D. Greguric and P. A. Pellegrini, Inorg. Chem. (1999), 38, 5502-5509.
  14. Research Conference Papers:

  15. Incorporating Sequence Specificity into Platinum(II) Compounds, D. Jaramillo and J. Aldrich-Wright, Abstracts Platinum Coordination Compounds in Cancer Chemotherapy, New York School of Medicine, USA (2003) Sup entry.
  16. The Structure-Activity Relationship of Chiral Square-Planar Platinum(II) Metallointercalators, D. Jaramillo, R. R. Fenton and J. Aldrich-Wright, Abstracts Platinum Coordination Compounds in Cancer Chemotherapy, New York School of Medicine, USA (2003) Sup entry
  17. Platinum(II) Intercalators as Potential Anti-Cancer Agents, R. R. Fenton, D. Fisher, J. R. Aldrich-Wright and P.J. Bednarski, Abstracts Platinum Coordination Compounds in Cancer Chemotherapy, New York School of Medicine, NY, USA (2003) 16.
  18. Square Planar Metallointercalators: Platinum(II) Anti-Cancer Complexes, D. Fisher, R. R. Fenton and J. R. Aldrich-Wright, Abstracts Platinum Coordination Compounds in Cancer Chemotherapy, New York School of Medicine, NY, USA (2003) 35.


Facilities

  • Varian Mercury 300 MHz Spectrometer
  • Varian Mercury 400 MHz Spectrometer
  • Varian Unity plus high resolution with micro imaging facilities 400 MHz Spectrometer
  • Bruker 200 MHz advance solid-state NMR spectrometer with magic angle spin
  • Cary Eclipse Fluorescence Spectrophotometer (Varian)
  • Cary 300 Bio UV-Vis Spectrophotometer (Varian)
  • Jasco J-810 CD/LD spectropolarimeter
  • Cannon-Manning semi-micro viscometer for Viscosity measurements
  • Electrophoresis and Footprinting equipment

International Linkages

Y. Tor (UCSD, USA)
B. Norden (Chalmers, Sweden)
A. Rodgers (Warwick, UK)
M. J. Hannon (Warwick, UK)
J. Kelly (Trinity, Dublin, IRE)
J. MacGarvey (Belfast, UK)