Structural dependence of flavonoid interactions with Cu2+ ions: implications for their antioxidant properties

TLDR

Flavonoids are a large group of polyphenolic phytochemicals that exhibit antioxidant activity in vitro. This study investigates how four structurally related flavonoids—quercetin, kaempferol, rutin, and luteolin—interact with Cu²⁺ ions, focusing on the influence of structural features on chelation versus oxidation. The authors examined Cu²⁺ binding and oxidative modification of these flavonoids, assessing chelate formation and oxidation pathways. The ortho 3′,4′‑dihydroxy substitution in the B ring promotes Cu²⁺ chelation and enhances antioxidant activity, while a 3‑hydroxy group increases oxidation of quercetin and kaempferol, luteolin and rutin lacking this group oxidize less, and LDL protection depends on chelation, oxidation, partitioning, and hydrogen‑donating properties.

Abstract

The flavonoids constitute a large group of polyphenolic phytochemicals with antioxidant properties in vitro. The interactions of four structurally related flavonoids (quercetin, kaempferol, rutin and luteolin) with Cu2+ ions were investigated in terms of the extent to which they undergo complex formation through chelation or modification through oxidation, as well as in their structural dependence. The ortho 3ʹ,4ʹ-dihydroxy substitution in the B ring is shown to be important for Cu2+-chelate formation, thereby influencing the antioxidant activity. The presence of a 3-hydroxy group in the flavonoid structure enhances the oxidation of quercetin and kaempferol, whereas luteolin and rutin, each lacking the 3-hydroxy group, do not oxidize as readily in the presence of Cu2+ ions. The results also demonstrate that the reactivities of the flavonoids in protecting low-density lipoprotein (LDL) against Cu2+ ion-induced oxidation are dependent on their structural properties in terms of the response of the particular flavonoid to Cu2+ ions, whether chelation or oxidation, their partitioning abilities between the aqueous compartment and the lipophilic environment within the LDL particle, and their hydrogen-donating antioxidant properties.