Cu(II) complexes of flavonoids in solution: Impact of the Cu(II) ion on the antioxidant and DNA-intercalating properties

Abstract

• Complexes of Cu(II) with flavonoids are studied in two solvents: DMSO and methanol. • Formation of complexes is monitored by UV-Vis spectroscopy and DFT calculations. • Kaempferol, luteolin and fisetin complexes show enhanced radical scavenging effect. • Molecular docking study indicates the interaction with DNA via intercalation. • Complexes may represent perspective therapeutics for neurodegenerative disorders. Flavonoids are naturally occurring polyphenolic compounds showing antioxidant and metal chelating properties. Chelation of the metal ion, e.g. , Cu(II), may significantly affect their activity in biological systems. Due to DNA-intercalating ability, metal complexes of flavonoids can act as therapeutics in the treatment of various human diseases, such as cancer or neurodegenerative diseases. In this work, antioxidant and DNA-intercalating properties of Cu(II)-flavonoid complexes are investigated using spectroscopic techniques and various computational approaches. The formation of stable Cu(II)-flavonoid complexes of kaempferol, luteolin, fisetin, and apigenin in two metal:ligand ratios (1:1 and 1:2) is confirmed by UV-Vis spectroscopy. DFT calculations indicate that Cu(II) ion adopts square planar coordination in Cu(II)-flavonoid (1:2) complexes. Radical scavenging activity of flavonoids in the presence/absence of Cu(II) ion is monitored using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. Except for apigenin, studied complexes show enhanced radical scavenging activity. Calculation results also imply that the presence of Cu(II) ion enhances acidity of OH groups in flavonoids. The molecular docking studies demonstrate that the formation of Cu(II)-flavonoid complexes (1:1 and/or 1:2) improves the DNA-intercalating ability of the parent flavonoids.