Flavonoid-Based Organometallics with Different Metal Centers - Investigations of the Effects on Reactivity and Cytotoxicity

Flavonol-derived Os-II(cym) and Rh-III-Cp* complexes were synthesized and the impact of the metal center on aqueous stability, reactivity toward biomolecules, and cytotoxic activity was compared to Ru-II analogs. The Rh-III complexes were the most stable to ligand release in aqueous solution and showed the highest preference for ubiquitin binding. Investigations on the reactivity toward nucleoside triphosphates revealed the clear affinity of Rh-III to 5-dATP, whereas Ru-II and Os-II prefer binding to 5-dGTP. Simultaneous incubation with amino acids and nucleoside triphosphates reveals the preference toward amino acids, indicating that binding to proteins might be a key step in the mechanism of action of this compound class. The complexes exhibit in vitro anticancer activities in the high nM to low M range, confirming the flavonol scaffold as a promising O,O-chelating ligand system for the development of anticancer active organometallics.