Zinc-Binding Sites on Selected Flavonoids

Flavonoids have attracted increased attention due to their broad bioactivities related to health and diseases. Modulating metal homeostasis may play an important role in their bioactivities. Recent studies have suggested that dietary flavonoids may affect zinc homeostasis, uptake, and transport. In this work, the zinc-binding sites on a few selected flavonoids have been investigated by 1H NMR spectroscopy under physiological relevant pH and the species formed were verified by mass spectrometry. Zinc binding induces distinct changes in the proton resonances on the flavonoid rings, providing useful information to locate the Zn-binding sites. No Zn-binding was observed with flavone which lacks a chelation site. Zinc was found to bind to the 3-hydroxyl-4-keto, catechol, and 5-hydroxyl-4-keto chelation sites of flavonol, 3′,4′-dihydroxylflavone and chrysin, respectively. Kaempferol and myricetin chelate zinc at the 3-hydroxyl-4-keto site while rutin binds zinc preferentially at the 5-hydroxyl-4-keto site. However, morin appears to bind zinc at the 1-ether-2-hydroxyl site.