The effect of flavonoids on the reduction of cupric ions, the copper-driven Fenton reaction and copper-triggered haemolysis

•24 structurally related flavonoids were tested.•Most of them were potent copper reductants.•Eight flavonoids potentiated copper-based Fenton reaction.•Most flavonoids protected erythrocytes against copper-triggered lysis.•5-hydroxyflavone was the only antioxidant compound in both assays. Flavonoids are considered beneficial, but they may exhibit pro-oxidative effects likely due to metal reducing properties. For the first time, 24 structurally related flavonoids were compared for copper reduction, and modulation of the copper-triggered Fenton reaction and lysis of erythrocytes. The vast majority of flavonoids reduced cupric ions; their behaviour ranged from progressive gradual reduction through bell-shaped, neutral, to a blockade of spontaneous reduction. Similarly, different behaviours were observed with the Fenton reaction. Flavone was the only flavonoid that potentiated copper-triggered haemolysis (155 ± 81 % at twice the amount of Cu2+), while 18 flavonoids were at least partly protective in some concentrations. Only 5-hydroxyflavone did not reduce Cu2+ and behaved as an antioxidant in both assays (reduction of 60 ± 10 % and 88 ± 1%, respectively, at an equimolar ratio with Cu2+). In conclusion, relatively subtle structural differences resulted in very different anti/prooxidant behaviour depending on the model.