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Whereas the isotope 99 of the element technetium (99Tc) is a fission product in nuclear power plants, its nuclear isomer 99mTc is the choice for the synthesis of radio probes for nuclear diagnostics. Both are important fields for society and require a fundamental understanding of the chemistry of this element. High-valent 99(m)Tc chemistry with complexes containing the fac-{99mTcO3}+ core is a rather new field. It gained much interest, since the reactivity of fac-99mTcO3}+ complexes with alkenes ((3+2) cycloaddition) enables a new labeling strategy for radiopharmaceutical applications and is a complement to established labeling procedures. Today, this new strategy is limited to one particular type of stabilizing tripodal ligand, 1,4,7-triazacyclononane (tacn) and its monosubstituted derivatives (tacn-R), due to the sterical pre-orientation and the strong sigma-donating nature of the nitrogen atoms in the tacn ligand. N-Heterocyclic carbenes (NHCs) are an interesting alternative for the established tacn-based ligands. NHCs are versatile strong electron donors (sigma-donor) which are known to stabilize metal centers in low and high oxidation states. In this project the suitability of tripodal NHCs as stabilizing ligands for high-valent 99(m)Tc and Re chemistry will be studied, aiming at the development of a high-valent organometallic technetium chemistry suitable for clinical translation. These studies will give a better understanding of the organometallic chemistry of technetium in comparison with rhenium and will help to close gaps in knowledge in ‘Fundamental Chemistry’. Due to the fact that the proposed class of compounds is essentially unknown, but has, according to our preliminary results, a multitude of activities and reactivities it will create new perspectives in technetium chemistry. This is essential, keeping in mind that the research with this important element is lagging behind that of its heavier congener rhenium. The synthesized Re-NHC compounds are of interest from a therapeutic point of view. Recently, NHC-complexes of copper-, silver-, gold- and palladium gained of much interest due to their promising antimicrobial and antitumor properties. In this context the evaluation of the bioactivity of the synthesized Re-NHC complexes will have an impact in the field of ‘Metals in Medicine’. Based on the fundamental research of rhenium and technetium with NHC ligands the development of an aqueous 99mTc-NHC chemistry will significantly influence the field of ‘Radiopharmacy and Nuclear Medicine’ and will widen the scope for 99mTc imaging probes in ‘Life Science’. Especially the synthesis of fac-{99mTcO3}+-NHC complexes and their application for labeling reactions following (3+2) cycloaddition strategies will paves the way for new opportunities in this upcoming field of 99mTc research. Furthermore, the impact of this project will not be limited to medicinal diagnostics or therapy; the investigation of the possibility of an aqueous organometallic chemistry (carbene chemistry) will be of general interest for the field of ‘Organometallic Chemistry’. Finally, this project has a strong educational aspect, since the training of (young) students in radionuclide chemistry working techniques is essential to prevent society from the foreseeable lack of scientists with experience in this important field.
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