The effect of Cu(II) ion on antioxidant and DNA-binding mechanism of baicalein and scutellarein: Spectroscopic, theoretical, and molecular docking study

Flavonoids are a group of polyphenolic compounds known to possess good radical scavenging activity. It was also shown that their anti/prooxidant properties are strongly structure-dependent and can be modified by metal ion binding. The structural parameters also appear to be key factors during their DNA-binding abilities. This work deals with spectroscopic and theoretical studies of two flavonoids, baicalein and scutellarein, alone, and in the presence of redox-active metal ion Cu(II). Cu(II) is the catalytic active ion in Fenton-like reactions and can enhance the production of reactive oxygen species or, when bound to the flavonoid, influence its antioxidant potential. UV-Vis spectroscopy showed that the electronic properties of the parent flavonoids are changed following the CuCl2 addition. Job's plot method revealed the 1:1 binding mode of interaction in DMSO and DMSO/PBS solvent. The ABTS(center dot+) assay showed only a negligible effect of Cu(II) presence on the antioxidant properties of baicalein and scutellarein. The mix of the natural reductant, glutathione, with flavonoids showed a synergistic effect in ABTS(center dot+) inhibition; however, this effect was suppressed by the presence of Cu(II). Absorption titration and molecular docking studies showed an effective DNA binding of both flavonoids that is further enhanced by the presence of Cu(II). DFT calculations were carried out to identify the most energetically stable Cu(II)-flavonoid structures as well as to determine the ability of their hydroxyl groups to undergo homolytic or heterolytic cleavage.