Iron binding of 3-hydroxychromone, 5-hydroxychromone, and sulfonated morin: Implications for the antioxidant activity of flavonols with competing metal binding sites

The iron binding properties and antioxidant activities of compounds with hydroxy-keto binding sites, 3-hydroxychromone, 5-hydroxychromone, and sulfonated morin were investigated. For these compounds, prevention of iron-mediated DNA damage and kinetics of FeII oxidation were studied in aqueous solutions close to physiological pH (pH 6). 3-Hydroxychromone and sulfonated morin inhibit iron-mediated DNA damage at lower concentrations than 5-hydroxychromone. All three compounds bind iron, but 3-hydroxychromone and sulfonated morin promote FeII oxidation much faster than 5-hydroxychromone. These results indicate that DNA damage inhibition by flavonols with competing hydroxy-keto binding sites is primarily due to iron binding at the 3-hydroxy-keto site. Iron oxidation rate also plays a significant role in antioxidant activity. In addition to iron binding and oxidation, reactive oxygen species scavenging occurs at high concentrations for the hydroxychromones. This study emphasizes the importance of iron binding in polyphenol antioxidant behavior and provides insights into the iron binding antioxidant activity of similar flavonols such as quercetin and myricetin.

Graphical abstractThe ability of 3-hydroxychromone, 5-hydroxychromone, and sulfonated morin to prevent iron-mediated DNA damage was examined, along with their iron binding properties. DNA damage inhibition is greater when iron binding occurs at the 3-hydroxychromone site. Iron binding alone does not determine antioxidant ability; iron oxidation also plays a significant role.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Iron binding is the primary antioxidant mechanism for flavonols. ► Antioxidant activity is controlled by FeII binding at the 3-hydroxy-keto site. ► FeII oxidation rate may significantly contribute to flavonol antioxidant activity.