Synthesis of D-fructose conjugated metal complexes and polymers for breast cancer targeting

The present thesis describes the synthesis, characterization and biological evaluation of D fructose conjugated molecules. The work focused on two different classes of compounds: On one hand low molar mass metal complexes and on the other hand polymers with complete different types of interaction with GLUT5 transporters. Literature studies revealed an increased uptake of D-fructose conjugated metal complexes into breast cancer cells mediated by the facilitative glucose transporter 5 (GLUT5) when compared to the D fructose free analogues, which showed no selective accumulation. To further evaluate this hypothesis, a derivative of the highly biological active molecule curcumin was used and conjugated to two units of D fructose by using the Cu(I) catalyzed alkine azide cycladdition. The β-diketo moiety of the curcumin derivative was used afterwards to form ruthenium complexes of the general formula [Ru(bpy)2(L)]Cl. The mentioned studies were limited to D fructose derivatives bound to the ligand scaffold via the C1 of the D fructose molecule. One major questions of the present thesis represented the influence of the substitution position. For this purpose, two novel D fructose conjugated ruthenium complexes starting from sucrose or a commercially available D fructose derivative, respectively, were synthesized. The D fructose units were attached via the C1 and C6 position by maintaining the rest of the molecules without further chemical modifications. All metal complexes were investigated for their biological properties. Additionally D fructosylated macromolecules were focused and the first literature-known, cationic polymer with covalently attached D fructose molecules could be contributed to this field. It showed superior biological properties in comparison to the sugar-free polymer. The last chapter represents the synthesis of poly(bromoethyl acrylates) and their full glycosylation in simple SN2 reactions in a post-polymerization functionalization process.


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