Research Topics of the Nanoscalic Systems Group
Liquid-liquid partition of radio-labeled substrates between aqueous/organic, two-phase systems ought to give precise and reliable quantitative data. These could then easily analyzed by using established software to yield the desired thermodynamic data such as extraction, distribution, association and stability constants. Mathematical treatment of extraction equilibrium may be applied to achieve information about the composition of the complexes extracted. Furthermore, important parameter such as lipophilicity for the prediction of absorption and distribution of radiotracers in bio-systems can be determined. The radiotracer technique allows precise determination, even at very low concentrations of the species in both phases.
Development of Copper-based Radiopharmaceuticals
Incorporation of copper(II) radioisotopes, such as 64CuII and 67CuII, into target-specific radiopharmaceuticals requires the use of chelate ligands to bind the radionuclide to a bioactive molecule. An important requirement is that the resulting radionuclide-ligand complex is both kinetically and thermodynamically stable in vivo, in order to minimize the release of the radionuclide to healthy tissue and therefore reduce the background for imaging and minimize radiation exposure to healthy tissue during therapy. A large variety of amine-based polydentate chelate agents, especially mono- and bi-cyclic polyamines, have been investigated in an effort to satisfy these requirements. However, bifunctional chelators, which permit the rapid, unsophisticated labeling of biologically active molecules and also achieve appropriate pharmaceutical targeting have not been described so far.
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.
Dendrimers constitute a unique class of three-dimensional molecules with a defined highly-branched symmetric architecture. These molecules are playing a continuously increasing role in different areas of science and technology. Their unusual chemical and physical properties result in them having very considerable potential for use in separation processes. The typical behavior of dendrimers is a reflection of their compact, tree-like molecular structure, providing an arrangement of inner and outer molecular functionalities which results in them being useful receptor and carrier molecules at the nanometer level. The enormous versatility and variety of dendritic structures offer intriguing opportunity particular in medicine.
The application of nanomaterials (NMs) in biomedicine is increasing rapidly and offers excellent prospects for the development of new non-invasive strategies for the diagnosis and treatment of cancer. One major advantage of NMs is their potential to be used as non-invasive diagnostic tools. By combining multiple modalities into a single probe, higher sensitivity can be achieved and thus deeper insight gained into different in vitro and in vivo processes.