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Grimminger, Philipp (2009): Rhenium(V)-Carbohydrate Complexes with Amino Acids. Dissertation, LMU München: Faculty of Chemistry and Pharmacy
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Abstract

This thesis is about the coordination chemistry of rhenium(V) with small biomolecules. Such rhenium complexes may be of medical significance in the field of radiopharmacy, since radioactive isotopes such as 186Re or 188Re are used for the diagnosis or treatment of tumors. But fundamental research is still necessary for the attachment of radiometals to biologically active molecules. Most rhenium(V)-based radiopharmaceuticals lack stability (at physiological conditions) or selectivity (in terms of targeting cells, or in terms of preparing an exactly defined agent). In order to meet these requirements, a library of ligands was scanned to synthesize kinetically inert mixed-ligand rhenium(V) complexes. Most of the prepared complexes (22 out of 28) were built with tri- and bidentate chelating ligands (“3 + 2” approach). They were studied by means of single-crystal X-ray diffraction, NMR spectroscopy, mass spectrometry, elemental analysis and other methods. As tridentate chelators, nitrogen containing compounds such as diethylenetriamine, rac-2,3-diaminopropionic acid, L-histidine, L-carnosine and other ligands based on amino acids were used. As bidentate chelators, an oxygen donor library was used, covering simple diols such as ethanediol or anhydroerythritol, and more complex molecules such as nucleosides, pyranosides, mono- and disaccharides or glycoside antibiotics. The optimum was found for a compound derived from the reducing disaccharide D-isomaltose and the dipeptide L-carnosine. It was possible to transfer the synthesis from standard laboratory conditions (millimolar concentration range, methanol as solvent, alkaline pH) to labeling experiments with 188Re (nanomolar concentration range, water as solvent, physiological pH). With this work, the chemistry of coordination compounds with rhenium(V) is extended to physiological conditions and the synthesized compounds are promising candidates for prospective works in the field of radiopharmacy.