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Carbohydrate-bearing ligands for biologically active metal ions

University of British Columbia

Two distinct projects involving carbohydrates in bioinorganic chemistry are discussed in this thesis. In one study, several gallium and indium complexes with pendant carbohydrates were prepared and examined for potential use in radiopharmaceutical applications. Carbohydrate-bearing 3-hydroxy-4-pyridinone ligand precursors and their tris(ligand)gallium(III) and indium(III) complexes were synthesized and characterized by mass spectrometry, elemental analysis, ]H and l 3C NMR spectroscopy, and in the case of one intermediate, by X-ray crystallography. With three equivalents of ligand, neutral complexes formed with the pyridinone moiety (as expected) complexing the gallium(III) and indium(III) metal centers. In the other study, a series of 3-hydroxy-4-pyridinones and their glycoside pro-drugs (pyridinone glycosides) were prepared and studied. The pyridinones have the potential to be used in metal chelation therapy to aid in the treatment of neurodegenerative disorders such as Alzheimer's disease. The pyridinone glycosides were synthesized via a Mitsunobu coupling and characterized by mass spectrometry, elemental analysis, !H and 1 3C NMR spectroscopy, and in one case by X-ray crystallography. The glycoside pro-drugs mask the metal chelation portion of the pyridinones by protecting the 3- hydroxy position. The glycosidic cleavage of the pyridinone glycosides was studied (and kinetic parameters determined for one compound) with Agrobacterium sp. P-glucosidase. This enzyme cleaves the pyridinone glycosides unmasking the pyridinones and making them available for metal chelation. A series of the 3-hydroxy-4-pyridinones also displayed significant antioxidant protection in a radical quenching assay.

Thesis/Dissertation

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2009-11-27

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http://hdl.handle.net/2429/15852

Chemistry

University of British Columbia

UBCV

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