Iron-binding properties of plant phenolics and cranberry's bio-effects

Abstract

The health benefits of cranberries have long been recognized. However, the mechanisms behind its function are poorly understood. We have investigated the iron-binding properties of quercetin, the major phenolic phytochemical present in cranberries, and other selected phenolic compounds (chrysin, 3-hydroxyflavone, 3′,4′-dihydroxy flavone, rutin, and flavone) in aqueous media using UV/vis, NMR and EPR spectroscopies and ESI-Mass spectrometry. Strong iron-binding properties have been confirmed for the compounds containing the “iron-binding motifs” identified in their structures. The apparent binding constants are estimated to be in the range of 10⁶ M⁻¹ to 10¹² M⁻² in phosphate buffer at pH 7.2. Surprisingly, quercetin binds Fe²⁺ even stronger than the well known Fe²⁺-chelator ferrozine at pH 7.2. This may be the first example of an oxygen-based ligand displaying stronger Fe²⁺-binding affinity than a strong nitrogen-based Fe²⁺-chelator. The strong Fe-binding properties of these phenolics argue that they may be effective in modulating cellular iron homeostasis under physiological conditions. Quercetin can completely suppress Fenton chemistry both at micromolar levels and in the presence of major cellular iron chelators like ATP or citrate. However, the radical scavenging activity of quercetin provides only partial protection against Fenton chemistry-mediated damage while Fe chelation by quercetin can completely inhibit Fenton chemistry, indicating that the chelation may be key to its antioxidant activity. These results demonstrate that quercetin and other phenolic compounds can effectively modulate iron biochemistry under physiologically relevant conditions, providing insight into the mechanism of action of bio-active phenolics.