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 10(6) M(-1) to 10(12) M(-2) in phosphate buffer at pH 7.2. Surprisingly, quercetin binds Fe(2+) even stronger than the well known Fe(2+)-chelator ferrozine at pH 7.2. This may be the first example of an oxygen-based ligand displaying stronger Fe(2+)-binding affinity than a strong nitrogen-based Fe(2+)-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.

Anti-inflammatory potential of 2-styrylchromones regarding their interference with arachidonic acid metabolic pathways

“…On the other hand, the spectral changes of those compounds upon addition of Fe(II) indicate the formation of iron complexes. The similar changes in all the compounds indicate that the Fe(II)-binding site is between the ortho-hydroxyl groups in the B-ring, considered to be one ''iron binding motif'' in flavonoid molecules [32,36]. Furthermore, the Fe(II) titration curves reveal the formation of 1:2 Fe(II):compound complexes (Fig.…”

“…The metal chelating activity was assessed by monitoring the changes in UV-vis spectrum of 2-SC after addition of Fe(II) [32]. Titration experiments were performed by sequential additions of 2 mL of FeCl 2 solution (300 mM stock solution) to 300 mL of a 10 mM (final concentration) 2-SC solution.…”

Iron sequestration is not the main mechanism in the inhibition of Staphylococcus aureus growth by cranberry phytochemicals

“…Phenolic materials in cranberries such as flavonoids, proanthocyanidins and anthocyanins may contain one or more ortho dihydroxyl phenolic and hydroxyketogroups with strong metal chelation property [18,21]. The binding constant for iron has been determined to be in the 10 6 M -1 range for the 1:1 catechol:iron complex [18]. It has been postulated that the antimicrobial effects of polyphenols might be derived from their iron chelating effects [9,18,22].…”

“…Quercetin, a cranberry flavonol, has also been shown to bind iron strongly not only through the ortho-dihydroxy group but also through the C3-hydroxy/C4-keto group of the C-ring and C5-hydroxy/C4-keto group of the A-and C-rings [18,19]. Cranberry proanthocyanidins have also been shown to bind iron strongly through the orthodihydroxy group of the B-ring [9].…”

A FRAP Assay at pH 7 unveils Extra Antioxidant Activity from Green, Black, White and Rooibos Tea but not Apple Tea

“…Ferrozine is widely applied for iron determination [18,19], for ascorbate determination and for monitoring iron-chelating reactions [20][21][22][23][24][25][26]. The reductions of Fe (III) by a variety of agents were monitored using ferrozine at pH 5-8.5 [27].…”