Radical Scavenging Efficiency of Flavonoids Increased by Calcium(II) Binding: Structure‐Activity Relationship

Abstract

Six structurally related flavonoids including two flavones apigenin and luteolin, one isoflavone genistein, and three flavonols, galangin, kaempferol and quercetin, are affected differently as radical scavengers by presence of Ca(II). Except for apigenin showing no reaction with Ca(II), other flavonoids all coordinate with Ca(II) to form 1 : 2 Ca(II)‐flavonoid complexes confirmed by UV‐vis and mass spectra. Coordination with Ca(II) for luteolin with the 3′, 4′‐catechol group and for flavonols with 3‐hydroxyl and 4‐carbonyl significantly enhance the DPPH• scavenging efficiencies shown by stopped‐flow spectra. Addition of Ca(II) shows no effect on radical scavenging rate of Genistein, as an isomer of apigenin, although both containing the same 4‐carbonyl and 5‐hydroxyl as a potential chelating group as confirmed by mass spectra and cyclic voltammetry. The two structure elements, 3′, 4′‐catechol and the combination of 3‐hydroxyl and 4‐carbonyl, are identified as important factors for Ca(II) enhancement of radical scavenging of flavonoids. Coordination of Ca(II) to kaempferol forming a 1 : 2 Ca(II)‐kaempferol complex at 3,4 site shows the most significant enhancement in radical scavenging efficiency by a factor of 4.4 compared to other investigated flavonoids.

Effects of Metal Ions on Antioxidant Activity of Red Wine

“…Similarly, the ABTS⋅ + kinetics of 5 μM CA, 5 μM GA, and CAT with 50 μM Ca(II) and Mg(II) also showed minimal alterations (Figures 3d–f). This suggests that there is no reaction occurring between polyphenols and Ca(II) or Mg(II), despite their concentrations being in the range of 1–10 mM, which has been reported to significantly enhance the antioxidant activity of flavonoids [15–16] …”

“…A significant body of research, including our recent work, has highlighted that the radical scavenging capacity of polyphenols, a key indicator of their antioxidant activity, is substantially altered when these compounds interact with metal ions. These interactions occur not only with transition metal ions such as Cu(II) and Zn(II) but also with main group metal ions like Ca(II), Mg(II), and Al(III) [13–17] …”

“…These interactions occur not only with transition metal ions such as Cu(II) and Zn(II) but also with main group metal ions like Ca(II), Mg(II), and Al(III). [13][14][15][16][17] Metal ions speciation including Mg(II), Ca(II), Fe(II/III), Cu(II), Zn(II) in wine has been measured in various studies. [18][19] Most metal ions are derived from soil, and some are from pollution like heavy metal ions, which may be introduced during grape growth and winemaking.…”

Double-Site Binding and Anti-/Pro-oxidation of Luteolin on Bovine Serum Albumin Mediated by Copper(II) Coordination

“… 8 A large number of studies including our recent work have shown that the radical scavenging ability as one of the main indicators of the antioxidant activity of flavonoids is significantly enhanced in a homogeneous ethanol or aqueous model system when the flavonoids are combined with metal ions like Cu(II) and Zn(II) and alkaline earth metal ions including Ca(II), Mg(II), Sr(II), and Ba(II). 9 − 12 …”

“…The physiological activities of flavonoids are mainly attributed to their antioxidant activities including radical scavenging, metal chelation, as well as enzymatic activity inhibition in forming reactive oxygen species (ROS) . A large number of studies including our recent work have shown that the radical scavenging ability as one of the main indicators of the antioxidant activity of flavonoids is significantly enhanced in a homogeneous ethanol or aqueous model system when the flavonoids are combined with metal ions like Cu­(II) and Zn­(II) and alkaline earth metal ions including Ca­(II), Mg­(II), Sr­(II), and Ba­(II). − …”