Modelling of Protective Mechanism of Iron(II)-polyphenol Binding with OH-related Molecular Descriptors

Abstract

Abstract:The linear models for the calculation of pIC50, pKa1 and Epa for 12 polyphenolic compounds (catechins, flavonols, catechol and gallol derivatives) were developed. As descriptors we used the number of vicinal (Nv) and non-vicinal (Nnv) OH groups, as well as the number of OH vicinal pairs as possible Fe 2+ chelate sites (Nch). The models gave r ˃ 0.9 and standard errors of 0.13, 0.26 and 0.04 for pIC50, pKa1 and Epa, respectively. For modelling of pIC50, Nch is better variable than Nv, and vice versa for modelling of pKa1 and Epa. This result, along with good correlations between pIC50, pKa1 and Epa, suggests two effects for antioxidative activity of polyphenols; their reaction(s) with OH and prevention of Fenton reaction by Fe 2+ chelation.

A new, simplified model for the estimation of polyphenol oxidation potentials based on the number of OH groups

“…The new model we have developed for the estimation of oxidation potentials of flavonoids based on the number of OH groups is simpler than our previous models (29)(30)(31) and yielded better statistics than the models reported in references 29 and 30. In addition, the model has turned out to be very stable, even though the inter-laboratory differences between experimental potentials were high (up to 0.096 V).…”

“…We reported similar correlations and proposed models for the estimation of E p1 based on OH-related descriptors (29)(30)(31).…”

Iron Complexes of Flavonoids-Antioxidant Capacity and Beyond

“…Flavonoids, with their multiple hydroxyl groups and the carbonyl group on ring C (flavones), have several available sites for metal complexation. Miličević et al noticed a strong correlation between polyphenols’ antioxidative activity and their affinity for Fe(II) ions (represented by binding constants), suggesting that the suppression of Fenton reaction is most probably caused by chelation of the ion [ 39 ]. Porfírio et al found that Fe(II) complex of morin, quercetin and fisetin (most probably 1:1) displayed higher antioxidant capacity for Ce(IV) (about 15%, 32% and 28%, respectively) than flavonoids alone [ 42 ].…”

“…Generally, we can say that flavonoid’s ability for ROS suppression, if we do not consider their effect on enzyme activity, is based mainly on their chelation of Fe(II) ions, optionally preceded by reduction of Fe(III) ions [ 39 , 71 , 72 ]. This effect is influenced by other factors such as pH and polarity of the reaction milieu [ 80 , 81 ].…”

“…A number of recent works showed that flavonoids (e.g., quercetin, baicalein, and baicalin) can form high-affinity complexes with transition metal ions, such as iron and copper [ 37 , 38 , 39 , 40 ]. This phenomenon is considered as the key mechanism of their biological activity (e.g., radical scavenging) [ 39 , 41 , 42 ]. Furthermore, metallocomplexes formed by iron chelation may display their own unique biological activities.…”