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Bioinorganic Group
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Welcome
A little introduction.. |
Metal Ions in Biology and Medicine
Metal ions are
of fundamental importance in biological processes, such as catalysis and
signalling. In this context, we are interested in the strategies used by nature
to selectively bind metal ions and to tune their reactivity.
The group has investigated how bacteria accumulate
essential elements, in particular molybdenum1 and iron2.
Since these two elements play a key role in the virulence of pathogenic
bacteria, this work now forms the basis for the development of novel
antibiotics (Siti Md Saleh, Diego Miranda, Orchidea Rogers, Stephen Milner).
Figure 1: Simplified
scheme illustrating the uptake of a
ferric-siderophore complex into a Gram-negative bacterial cell.
As illustrated above, bacteria secrete siderophores to
scavenge iron from their environment. We have been able to identify several of
the chemical design principles that enable such siderophores to bind iron and
molybdenum selectively and with high affinity. We are now applying these principles
to other areas of chemistry, for example in the development of luminescent
chemosensors for oxometalates3(Helen Batey, Anna Peacock, Nicole Reddig), the development of luminescent
probes for xanthine oxidase (Libby Gibson) and integral membrane proteins
(Catherine Davies). In addition, we use siderophore analogues in the
self-assembly of large metal-containing clusters (Emma Brown)4
and helicates.
Figure 2:
The luminescent sensor molecule shown signals the presence of molybdate (MoO42-) by a decrease in emission intensity.
The coordination chemistry of molybdenum is central to our work
on molybdenum-containing enzymes. In this area, we are working on the
development of novel xanthine oxidase inhibitors for the treatment of gout and
on small molecule models for the active site of CO-dehydrogenase (Nicola Smith,Thanh Vu, Claudia Raendler,
Sarah David).
Figure 3: The solid state structures of two biomimetic
Mo-complexes.
Selected references:
1. A.-K. Duhme-Klair, H. H.
Khodr, R. C. Hider, J. Biol. Inorg. Chem., 7, 891 (2002).
2. A. Müller, A. J.
Wilkinson, K. S. Wilson, A.-K. Duhme-Klair, Angew. Chem. Int. Ed. Engl., 45, 5132 (2006).
3. A. F. A. Peacock, H. D. Batey, C. Raendler,
A. C. Whitwood, R. N. Perutz, A.-K. Duhme-Klair, Angew. Chem. Int. Ed., 44,
1712 (2005).
4. J. Brown, A-K. Duhme-Klair, M. I. Elliot, J. E. Thomas-Oates, P. L. Timmins, P. H. Walton, Angew. Chem. Int. Ed., 44, 1392 (2005)
Copyright © Anne-K Duhme-Klair, webmaster Siti Md-Saleh 2009. All right reserved
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