In: Coordination Chemistry Research Progress ISBN 978-1-60456-047-3 Editors: T.W. Cartere, K.S. Verley, pp. 305-328 © 2008 Nova Science Publishers, Inc. Chapter 10 COMPLEXATION AND ANTIOXIDANT ACTIVITY OF FLAVONOIDS WITH BIOLOGICALLY RELEVANT METAL IONS Sixto Domínguez a , Julia Torres b , Paula Morales b , Horacio Heinzen c , Ana Bertucci c , and Carlos Kremer b a Departamento de Química Inorgánica, Universidad de La Laguna, Tenerife, Canary Islands, Spain b Cátedra de Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, CC 1157, Montevideo, Uruguay c Cátedra de Farmacognosia, Departamento de Química Orgánica, Facultad de Química, Universidad de la República, CC 1157, Montevideo, Uruguay ABSTRACT Flavonoids are phenolic substances present in substantial amounts in vascular plants. Among the many significant medicinal and nutritional values, antioxidant properties of flavonoids have been by far the most studied. These molecules interact strongly with cations, and the experimental evidence show that the antioxidant activity is modified by the presence of metal ions. The research on the structure-activity relationship has been hampered by the lack of a full understanding of the interaction of flavonoids with biologically relevant cations. In this work we report a detailed potentiometric study of the complexation of flavonoids (quercetin, rutin, rhamnetin and isorhamnetin) with Mg 2+ , Ca 2+ , Cu 2+ , Zn 2+ , Mn 2+ , Fe 2+ , Fe 3+ and Al 3+ at 25.0 °C and I = 0.15 M NaClO 4 . UV-vis spectra studies of some selected systems in methanolic solution and the characterization of complexes in the solid state are also included. Besides, we report the study of the free radical scavenging activity of the ligands and their corresponding metal complexes. The results show the formation of stable species of flavonoids with these metal ions, having a 1:1 metal to ligand ratio. The flavonoids are present in these species either fully or partially deprotonated. The observed free radical scavenging activity of flavonoid:metal ion mixtures (equimolar amounts) was always similar to that observed for the flavonoids alone under the same conditions. The unique case in which the activity is markedly increased upon addition of the metal ion is Cu-quercetin. But, when one equivalent of