Book of Abstracts - Ruhr-Universität Bochum

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ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
The [CpM(CO)3] - Moiety (M = Mn, Tc, Re) as Phenyl Ring analog – a Promising
Strategy Towards New Drugs and Radiopharmaceuticals
D. Can, H.P. N'Dongo, P. Schmutz and R. Alberto*
University of Zurich, Faculty of Inorganic Chemistry, Winterthurerstrasse 190, 8057 Zurich,
Switzerland.
E-mail: daniel.can@aci.uzh.ch
Structural changes imposed on proteins or nucleic acids by metal cations such as Ca 2+ or Zn 2+ are
essential for the initiation of biological processes. Organometallic complexes are comparably rare as
structural recognition site in receptors, whereas exactly this is how most organic molecules and drugs
tend to work 1 .
As early as 1979 Hanzlik et al. studied the interaction of �-Ferrocenylalanine with phenylalanine
hydroxylase and phenylalanine decarboxylase and showed that the ferrocene derivative behaved like
phenylalanine analogues 2 . Ongoing investigations by Jaouen et al. showed years later, that substitution
of a phenyl ring in tamoxifen by ferrocene similarly kept the biological activity of the lead compound
intact 3 .
As 99m Tc is nowadays in the focus of the development of radiotracers, introducing group 7 transition
metals as [CpM(CO)3] into this analogy opens new directions not only towards new drugs but also
towards very promising radiopharmaceuticals.
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Following this strategy we will present the analogy of different classes of bioactive compounds
containing [CpRe(CO)3]: sulphonamides acting as carbonic anhydrase inhibitors with high binding
affinities 5 , histone deacetylase inhibitors, amino acids transported by the LAT1 transporter and
melanoma imaging agents with melanin afiinity.
Herein we describe the synthesis and characterization of "cold" Re-compounds as surrogates to well
known pharmaceuticals and discuss their analogy. For the "hot" molecules, we followed a general
aqueous approach towards 99m Tc(CO)3 labeled � 5 -Cp derivatives from their dimeric Cp species via
metal mediated retro-Diels-Alder reaction 4 and show that the conditions used can be applied to a
variety of functional groups.
References
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1. S. J. Lippard, J. M. Berg, Principles of Bioinorganic Chemistry, University Science Books, Mill
Valley, CA, 1994
2. R. P. Hanzlik, P. Soine, W. H. Soine, J. Med. Chem., 1979, 22, 424-428
3. G. Jaouen, S. Top, A. Vessière, Bioorganometallics, Wiley-VCH, Weinheim, 2006, p. 65
4. Y. Liu, B. Spingler, P. Schmutz et al, J. Am. Chem. Soc., 2008, 130, 1554-1555
5. C. T. Supuran, Nature, 2008, 7, 168-181
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