Research

Due to a genetic defect, sulfite oxidase, which is responsible for catalysing the last step in sulfur metabolism, might not work. The results are severe neuronal dysfunctions that lead to general underdevelopment, above all of the brain, which usually means that those affected do not reach the end of their first year of life. The only current therapy for the three forms of this illness is the synthesis of a molybdopterin precursor compound (cPMP) and its injection into the liver. The illness could be fully healed in case of the specific Moco deficiency type A. However, this does not work for othe MocoD types or “isolated Sulfite Oxidase Deficiency” (iSOD). The studies performed by our research group have suggested that the influence of the molybdopterin ligand is most important with regard to the pyran and the pyrazine rings and the most pressing goal is the synthesis of a corresponding model that is able to coordinate to molybdenum via a dithiolene moiety. After developing a synthetic model of such kind, we plan to test it on its possible therapeutic effect with regard to encephalopathy caused by the dysfunction of sulfite oxidase. This will be carried out at first in cooperation with a microbiology research group (Leimkühler/Potsdam) and later ideally with a medical facility. By doing so, we hope to develop a better method of treatment those types of illness that are currently not treatable. The project is a continuation, refinement and enhancement of earlier research approaches.

Dithiolenes are also excellent ligands for thiophile metals such as mercury, lead, arsenic, but also nickel. Combining dithiolenes with fluorophores by using suitable linkers has a great potential in the area concerned with fluorescence-based detection or tracking/observation of the corresponding metals, for example in cell samples. The non-innocence of the dithiolene function should guarantee an excellent signal transduction when bound with metal, as these ligands are predestined to establish a compound between the connected metal and fluorophore. Furthermore, the modification of the dithiolenes with further metal-binding groups should enable a greater metal specificity in the further development of the project. My Group is currently developing and optimising different combinations of dithiolene moiety, linker and fluorophore. First results for identifying metals by using different chemosensors have been successful (registered for patent), or are exceedingly promising.

It has already been proven that vanadium compounds are able to catalyse the enantioselective synthesis of sulphoxides, which are valuable reagents in organic synthesis. To this effect, we are currently developing compounds, in which vanadium is combined with dithiolene ligands and testing them for corresponding activity. Based on the non-innocent character of the dithiolenes, we expect to see significant deviations in the reactivity when compared to the compounds which have previously been reported. The reduction of the oxygen which is to be transferred at the vanadium centre, should be simplified by the dithiolene ligands, which can release electrons and should therefore lead to increased efficiency. Conversion, yield and enantioselectivity will be examined in detail.