Dr Matthew H Todd BA, PhD (Cantab)

Lecturer in Organic Chemistry

School of Chemistry
University of Sydney
NSW 2006
Australia
Tel: +61 2 9351 2180
Fax: +61 2 9351 3329
email: M.Todd@chem.usyd.edu.au

Research Interests

MERS- Molecularly Engineered Recognition Scaffolds. We have recently begun a major new BBSRC-funded initiative in collaboration with Mike Watkinson’s group at Queen Mary, University of London, and with Lisa Hall’s group at Cambridge towards new medical devices for the early detection of various disease states. The project is a flagship for new directions in the biosensor field, in which we are involved through the UK Analytical Partnership.


Schematic of section through two array sites for an SPR biochip with molecular recognition constructs having inbuilt SPR amplifiers

Antiparasitic Drug Discovery. We are part of a major consortium of international researchers from various disciplines addressing a serious public health concern – the development of new drugs for the treatment of schistosomiasis (bilharzia), to replace the sole existing drug praziquantel. The project encompasses solid phase organic synthesis, computational drug discovery, biochemistry, parasitology and proteomics. We are grateful for support for this programme from the EU, the University of Sydney, the British Council and the University of London Central Research Fund. We are also coordinating the schisto activities in the new Open Source biomedical research community known as The Synaptic Leap.


The snail that acts as intermediate host to the parasite responsible for Schistosomiasis.

Nonlinear Effects in Asymmetric Catalysis. We wish to understand the extent and mechanism of nonlinear effects in asymmetric catalysis, whereby reaction product e.e. may be enhanced with respect to catalyst e.e.. The prediction of such effects would allow us to design ligands generating large e.e. enhancements. An understanding of these processes feeds into our interest in asymmetric autocatalysis. The Soai reaction involves the asymmetric amplification of a pyrimidyl alcohol at the expense of its enantiomer. We aim to understand the extent of such reactions and thereby to educate a search for other examples. This work has potentially great relevance in the understanding of the origin of biochemical homochirality, which is its blue-skies focus.

Autocatalytic reactions without a nonlinear effect lead to an inexorable decrease in e.e.

Peptidomimetic Methodology. We have an ongoing interest in the stereoselective synthesis of scaffolds for peptidomimetic compounds, in particular those derived from pyrazinone ring systems. This work is the feeder for several other projects, such as our interest in biosensors and the synthesis of new beta-turn mimics. We have also recently developed, in collaboration with Ismail's group in Cairo, potent new drugs for the treatment of hypertension.


Overlay of Tendamistat Trp-Arg-Tyr beta-turn with designed mimic

Synthetic Nucleases. Synthesis and evaluation of new metallosynzymes with sequence-selectivity in the cleavage of double-stranded DNA. (with Mike Watkinson (Queen Mary, London) and David Benoit (Ulm)).


Other areas of interest a) The prediction of resistance mechanisms to the magainin class of pore-forming peptide antibiotics. b) New techniques in computer-aided synthetic design.

 


Group Picture August 2006 (From left: MHT, Thiru Thirukkumaran (Grad Dip), Clement Pontoizeau (summer student), Taliesha Paine (Honours), Wing Yan Leung (Honours), Shaimaa El-Fayyoumy (PhD).

 

 


Bowling on Shaimaa's Last Day in Sydney (From left: MHT, Adhi Ramana (Postdoc), Wing Yan Leung, Thiru Thirukkumaran, Tomasz Wyczesany (PhD), Shaimaa El-Fayyoumy and Taliesha Paine.

 

November 2006 - Launch of the new open access Chemistry Central Journal. Submit papers now!


 

Recent Media Highlights

·         Radio Interview on Open Source Science

·         Synaptic Leap featured in Cell Article on Open Source Drug Discovery

 

Selected Recent Publications

·         A Highly Selective Click-Generated Zinc(II) Sensor, E. Tamanini, M. H. Todd and M. Watkinson, submitted.

·         Click-generated Scorpion Complexes for the Detection of Biological Recognition Events, E. Tamanini, S. E. J. Rigby, M. Motevalli, M. H. Todd and M. Watkinson, submitted.

·         Synthesis and DNA binding ability of cyclam-amino acid conjugates, A. V. Ramana, M. Watkinson and M. H. Todd, Bioorg. Med. Chem. Lett., 2008, in press.

·         Effective Methods for the Biotinylation of Azamacrocycles, S. Krivickas, E. Tamanini, M. H. Todd and M. Watkinson, J. Org. Chem., 2007, 72, 8280-8289.

·         Is Actin the Praziquantel Receptor?, A. R. Troiani, L. Pica-Mattoccia, C. Valle, D. Cioli, G. Mignogna, F. Ronketti and M. H. Todd, International Journal of Antimicrobial Agents, 2007, 30, 280-281.

·         Praziquantel Analogues. I. Modification of the Aromatic Ring, F. E. Ronketti, A. V. Ramana, X. Chao-Ming, L. Pica-Mattoccia, D. Cioli and M. H. Todd, Bioorg. Med. Chem. Lett., 2007, 17, 4154-4157.

·         Open Access and Open Source in Chemistry, M. H. Todd, Chemistry Central Journal, 2007, 1:3.Open Access Here.

·         The Effects of Drugs, Ions and Poly-L-lysine on the Excretory System of Schistosoma mansoni, J. R. Kusel, F. Oliveira, M. H. Todd, F. E. Ronketti, S. Lima, A.-C. de Mattos, K. Teixeira, P. M. Z. Coelho, J. A. Thornhill and F. Ribeiro, Mem. Inst. Oswaldo. Cruz., 2006, 101 (Suppl. 1), 293-298. Download.

·         Improved Synthesis of the Valuable Peptidomimetic Intermediate 3-Azido-4-hydroxy Cyclopentanoic Acid, E. Tamanini, M. Watkinson and M. H. Todd, Tetrahedron: Asymmetry, 2006, 17, 2235-2239.

·         Open Source Research - The Power of Us, T. B. Kepler, M. A. Marti-Renom, S. M. Maurer, A. K. Rai, G. Taylor and M. H. Todd, Aust. J. Chem., 2006, 59, 291-294. Open access article here.

·         Design and Synthesis of New Tetrazolyl- and Carboxy-biphenylylmethyl quinazoline Derivatives as Angiotensin II AT1 Receptor Antagonists, Mohamed A. H. Ismail, Stewart Barker, Dalal A. Abou El Ella, Khaled A. M. Abouzid, Rabab A. Toubar and M. H. Todd, J. Med. Chem., 2006, 49, 1526-1535.

·         Solid Phase Synthesis of Praziquantel, W. Mansour, S. El-Fayoummy and M. H. Todd, Tetrahedron Lett., 2006, 47, 1287-1290.

·         (R)-4-Hydroxymethyl-2-ferrocenyloxazoline, S. El-Fayoummy, M. E. Motevalli, C. J. Richards and M. H. Todd, Acta Cryst E., 2006, E62, m719-m720.

·         Computer-Aided Organic Synthesis, M. H. Todd, Chem. Soc. Rev., 2005, 34, 247-266.

·         Drugs for the Control of Parasitic Diseases: Current Status and Development. Schistosomiasis, A. Fenwick, L. Savioli, D. Engels, R. Bergquist and M. H. Todd, Trends in Parasitology, 2003, 19, 509-515.

·         Amino Acid-Derived Heterocycles: Lewis Acid-Catalyzed and Radical Cyclizations from Peptide Acetals, M. H. Todd, C. O. Ndubaku and P. A. Bartlett, J. Org. Chem., 2002, 67, 3985-3988.

·         Use of Fourier Transform Ion Cyclotron Resonance Mass Spectrometry in the Tagging of a Combinatorial Library, M. H. Todd and C. Abell, The Analyst, 2002, 127, 1399-1406.

·         Asymmetric Autocatalysis: Product Recruitment for the Increase in the Chiral Environment (PRICE), M. H. Todd, Chem. Soc. Rev., 2002, 31, 211-222.

·         Novel Chemical Tagging Method for Combinatorial Synthesis Utilizing Suzuki Chemistry and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry, M. H. Todd and C. Abell, J. Comb. Chem., 2001, 3, 319-327.

Recent Presentations

·         ‘Putting a Price on Success - Enantioselective Synthesis for Tropical Diseases,’ Sydney-SIOC New Chemical Technologies Workshop, Shanghai Institute of Organic Chemistry, China, November 2007

·         ‘Azamacrocyclic Complexes for Biomedical Applications,’ ICHC-21, Sydney, July 2007

·         ‘Searching for Unusual Behaviour in Asymmetric Chemical Reactions,’ UNSW, Sydney, June 2007

·         ‘Drug Discovery for Neglected Diseases - the Case of Praziquantel,’ Eskitis Institute, Griffith University, Brisbane, May 2007

·         ‘Anticipating the Inevitable - Drug Discovery for Tropical Diseases,’ University of Queensland, Brisbane, May 2007

·         ‘Azamacrocyclic Complexes for Biomedical Applications,’ ISCOC-9, Singapore, December 2006

·         ‘New Ideas in Treating Major Tropical Diseases,’ NUS, Singapore, November 2006

·         ‘Nonlinear Effects in Asymmetric Catalysis,’ Peking University, Beijing, September 2006

·         ‘Open Source Drug Discovery for Tropical Diseases,’ ICOPA XI, Glasgow, UK, August 2006.

·         ‘Chemistry and Biology of Praziquantel,’ ICOPA XI, Glasgow, UK, August 2006.

·         ‘Fluorescent Praziquantel single-handed,’ invited presentation at Third EU Concerted Action on Praziquantel, Luxor, Egypt, March 2005.

·         ‘Chemistry of the Enediamides,’ University of Yaoundé, Cameroon, March 2004.

·         ‘Chemistry and Biology of Praziquantel,’ invited presentation at Second EU Concerted Action on Praziquantel, Yaoundé, Cameroon, March 22nd 2004.

·         ‘Handshakes for Tranducing Assemblies,’ invited presentation at ‘Biomimetic Tranduction Mechanisms,’ London, 14th Jan 2004.

·         ‘How to give a Seminar,’ Institute of Commonwealth Studies, London. 13th November 2003.

·         ‘Synthetic Control in Biomimetic Chemistry,’ Institute of Biotechnology, Cambridge University. 30th October 2003.

·         ‘Chemical and Biological Promise of Enediamides,’ University of Stellenbosch, Republic of South Africa. March 2003.

Teaching and Group Resources

Mat's lecture notes, handouts and group documents are here.