Mid-Term Report Summary - MOCOMODELS (Synthesis of mono-dithiolene molybdenum complexes and their evaluation as potential drugs for the treatment of human isolated sulfite oxidase deficiency.)
Many complexes made in course of our work were investigated for their catalytic potential and it was found that those with aliphatic (i.e. non-aromatic) substituents on the dithiolene moiety were far more reactive yet also far more labile than those with aromatic substituents. By combining aliphatic and aromatic functions in our substituents we hope to eventually be able to meet the delicate balance between stability and reactivity required for the complexes suitable for re-constituting activity of the apo-enzyme.
In course of the work towards the project's aims two very unexpected, hence unanticipated discoveries were made. We found that a method very frequently used in many labs of different specialisation for the de-protection of dithiolene precursors is actually fully reversible. Given that the side product of the reaction is CO2, this means that the de-protected version of a dithiolene ligand may serve as an effective trap for the greenhouse gas. The second unexpected finding was made while trying to generate dithiolene complexes from alkynes and a molybdenum sulfur complex. Instead of the desired complex a so called pentathiepin (a sulfur rich organic compound) was made. As there are some natural products with this chemical motif having antibacterial and fungicidal properties, we investigated the respective reaction further and were able to synthesise a set of pentathiepins of unprecedented complexity, which even showed interesting DNA binding behaviour. These compounds were then tested for their activity against four different cancer cell lines and it was found that they could very well compete in this respect with carboplatin, a chemotherapeutic agent frequently administered to cancer patients. By accident we may have found a promising new class of compounds well equipped for treating cancer patients.