The flavanol (±)-catechin shows an OH group but no 4-keto group on ring C (C3), and no conjugation between ring A and B. The related flavanone (+)-eriodictyol has a keto group on C4 but no 3-OH group on ring C. (+)-Taxifolin, another flavanone, has an OH on C3 and a keto group on C4 of the C ring. Deoxyribose degradation assay systems, with hydrogen peroxide and ascorbic acid either added or omitted, were performed in variants in which Fe(III) was added in a complex with ethylenediaminetetraacetic acid (EDTA). In combination with differential pulse voltammetry (DVP), the specific redox-chemical contributions of the ring A m-dihydroxyl groups could be explored more specifically in addition to those of the traditionally investigated o-dihydroxyl groups of ring B.

Quinolinic acid (2,3-pyridinedicarboxylic acid, QUIN) is a well-known neurotoxin. Consequently, QUIN could produce reactive oxygen species (ROS). ROS are generated in reactions catalyzed by transition metals, especially iron (Fe). QUIN can form coordination complexes with iron. A combination of differential pulse voltammetry, deoxyribose degradation and Fe(II) autoxidation assays was used for explorating ROS formation in redox reactions that are catalyzed by iron in QUIN-Fe complexes. Differential pulse voltammetry showed an anodic shift of the iron redox potential if iron was liganded by QUIN. In the H₂O₂/FeCl₃/ascorbic acid variant of the deoxyribose degradation assay, the dose-response curve was U-shaped. In the FeCl₃/ascorbic acid variant, QUIN unambiguously showed antioxidant effects. In the Fe(II) autoxidation assay, QUIN decreased the rate of ROS production caused by Fe(II) oxidation. Our study confirms that QUIN toxicity may be caused by ROS generation via the Fenton reaction. This, however, applies only for unnaturally high concentrations that were used in attempts to provide support for the neurotoxic effect. In lower concentrations, we show that by liganding iron, QUIN affects the Fe(II)/Fe(III) ratios that are beneficial to homeostasis. Our results support the notion that redox chemistry can contribute to explaining the hormetic dose-response effects.

Background: The alkaloid 8-hydroxyquinoline (8HQ) is well-known for various biological activities, including antioxidant effects and especially for the formation of coordination complexes with various transition metals, such as iron, amongst others. Therefore, 8HQ was extensively explored as a promising antineurodegenerative agent. However, other authors noted pro-oxidant effects of 8HQ. Here, we explore the pro- and antioxidant properties of 8HQ, especially in context of coordination complexes with iron (II) and iron (III). Methods: Nano-electrospray−mass spectrometry, differential pulse voltammetry, deoxyribose degradation, iron (II) autoxidation, and brine shrimp mortality assays were used. Results: 8HQ formed a complex mixture of coordination complexes with iron (II) and iron (III). Furthermore, 8HQ showed antioxidant effects but no pro-oxidant ones. In the brine shrimp mortality assay, 8HQ demonstrated toxicity that decreased in the presence of iron (III). Conclusions: 8HQ is a potent antioxidant whose effects depend not only on the formation of the coordination complexes with iron ions, but surely on the scavenging activities due to the redox properties of the 8-hydroxyl group. No pro-oxidant effects were observed in the set of the used assays.

Reactive oxygen species (ROS) are known for their participation in various physiological and pathological processes in organisms, including ageing or degeneration. Kynurenine pathway metabolites, such as kynurenic (KYNA) or xanthurenic (XA) acid, can affect neurodegenerative diseases due to their ROS scavenging and Fe ion coordination complex formation but insights are still incomplete. Therefore, we investigated the formation and antioxidant capabilities of KYNA– and XA–Fe complexes by nano-electrospray−mass spectrometry, differential pulse voltammetry, deoxyribose degradation and Fe^II autoxidation assays. XA formed coordination complexes with Fe^II or Fe^III ions and was an effective antioxidant. By contrast, only Fe^II–KYNA complexes could be detected. Moreover, KYNA showed no antioxidant effects in the FeCl₃/ascorbic acid deoxyribose degradation assay variant and only negligible activities in the Fe^II autoxidation assay. Coordination complexes of Fe ions with KYNA probably stabilize KYNA in its keto tautomer form. Nevertheless, both KYNA and XA exhibited sufficient antioxidant activities in some of the employed assay variants. The results provide evidence that both have the potential to alleviate neurodegenerative diseases by helping to maintain tissue redox homeodynamics.

Flavonoids are rather common plant phenolic constituents that are known for potent antioxidant effects and can be beneficial for human health. Flavonoids with a pyrogallol moiety are highly efficient reducing agents with possible pro- and antioxidant effects, depending on the reaction milieu. Therefore, the redox properties of myricetin and tricetin were investigated by differential pulse voltammetry and deoxyribose degradation assay. Tricetin proved to be a good antioxidant but only showed negligible pro-oxidant activity in one of the deoxyribose degradation assay variants. Compared to tricetin, myricetin showed pro- and antioxidant effects. The more efficient reducing properties of myricetin are probably caused by the positive mesomeric effect of the enolic 3-hydroxy group on ring C. It is evident that the antioxidant properties of structurally similar flavonoids can be converted to apparent pro-oxidant effects by relatively small structural changes, such as hydroxylation. Since reactive oxygen species (ROS) often serve as secondary messengers in pathological and physiological processes in animal and plant cells, the pro- and antioxidant properties of flavonoids are an important part of controlling mechanisms of tissue signal cascades.

Iron is an essential co-factor for many enzymes that catalyze electron transfer reactions. It is well known that so-called “poorly liganded” iron can increase ROS concentrations and trigger oxidative stress that is capable of initiating apoptosis. Conversely, controlled ROS production has been recognized as an integral part of cellular signaling. Elevated ROS concentrations are associated with aging, inflammatory and degenerative diseases. Anti-aging properties have been attributed especially to antioxidant phenolic plant metabolites that represent food additives in our diet. Consequently, this study explores the effects of flavonoids (quercetin and rutin), several phenolic acids (caffeic, chlorogenic, and protocatechuic acid), and the alkaloid caffeine on iron(II) autoxidation and ROS production in comparison to the standard antioxidants ascorbic acid and Trolox. The iron(II) autoxidation assay was carried out in pH 6.0 (plant apoplast and inflamed human tissue) and 7.4 (cell cytoplasm and human blood plasma). The obtained results accentuate phenolic acids as the more specific antioxidants compared to ascorbic acid and Trolox. Flavonoid redox chemistry depends more on the chemical milieu, specifically on pH. In vivo, the presence of iron cannot be ruled out and “wrongly” or “poorly” complexed iron has been pointed out as causative agent of various age-related diseases.