Polynuclear Cluster Compounds
Polynuclear metal compounds may have considerable potential as metallic drugs. The most prominent representatives are polyoxometalates which have been investigated since the last third of the 19th century. In addition to applications in catalysis, separation, analysis, and as electron-dense imaging agents, some of these substances have been shown to exhibit biological activity in vitro as well as in vivo ranging from anti-cancer, antibiotic, and antiviral to anti-diabetic effects. On the way to explore the biological activity of polynuclear cluster compounds, we recently recognised polyoxometalates as a new class of potent enzyme inhibitors. Certain polymetalates are able to inhibit E-NTPDases (ecto-nucleoside triphosphate diphosphohydrolases) that are surface-located nucleotide-hydrolyzing enzymes involved in the regulation of signaling cascades by activating G protein-coupled P2 receptors. The most potent compound - described to date – is K6H2[TiW11CoO40] I exhibiting Ki values which are significantly lower than those of known standard inhibitors. A further promising new class of cluster compounds to permit selective inhibition of E-NTPDases are hexanuclear rhenium complexes II with bridging sulfur, selenium and/or tellurium atoms.
C. E. Müller, J. Iqbal, Y. Baqi, H. Zimmermann, A. Röllich, H. Stephan
Polyoxometalates – a new class of potent ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) inhibitors
Bioorg. Med. Chem. Lett. 2006, 16, 5943-5947.
T. Meißner, R. Bergmann, J. Oswald, K. Rode, H. Stephan, W. Richter, H. Zänker, W. Kraus. F. Emmerling, G. Reck
Chitosan-encapsulated Keggin anion [Ti2W10PO40]7-: Synthesis, characterization and cell uptake studies
Transition Met. Chem. 2006, 31, 603-610.
M. A. Shestopalov, Y. V. Mironov, K. A. Brylev, D. Y. Naumov, V. E. Fedorov, H. Spies, H.-J. Pietzsch,
H. Stephan, G. Geipel, G. Bernhard
Cluster Core Controlled Reaction of Substitution of terminal Bromide Ligands by Triphenylphosphine in Octahedral Rhenium Chalcobromide Complexes
J. Am. Chem. Soc. 2007, 129, 3714-3721.
F. M. Sansom, P. Riedmaier, H. J. Newton, M. A. Dunstone, C. E. Müller, H. Stephan,
E. Byres, T. Beddoe, J. Rossjohn, P. J. Cowan, A. J. F. d’Apice, S. C. Robson, E. L. Hartland
Enzymatic properties of an ecto-nucleoside triphosphate diphosphohydrolase from Legionella pneumophila: substrate specificity and requirements for virulence
J. Biol. Chem. 2008, 283, 12909-12918.
K. A. Brylev, Y. V. Mironov, S. Kozlova, V. E. Fedorov, S.-J. Kim, H.-J. Pietzsch, H. Stephan,
A. Ito, S. Ishizaka, N. Kitamura
The First Octahedral Cluster Complexes With Terminal Formate Ligands: Synthesis, Structure and Properties of K4[Re6S8(HCOO)6] and Cs4[Re6S8(HCOO)6]
Inorg. Chem. 2009, 48, 2309-2315.
H. Stephan, M. Kubeil, F. Emmerling, C. E. Müller
Polyoxometalates as versatile enzyme inhibitors
Eur. J. Inorg. Chem. 2013, 48, 1585-1594.