Šárka Ramešová

The oxidation of natural flavonoid quercetin

This study explains the controversies in the literature concerning the number of electrons involved in the oxidation of quercetin. This stems from inappropriate handling samples, which require strict anaerobic conditions. The redox potential of quercetin strongly depends on the pH and on the presence of dissociation forms in solution.

On the stability of the bioactive flavonoids quercetin and luteolin under oxygen-free conditions

AbstractThe natural flavonoid compounds quercetin (3,3′,4′,5,7-pentahydroxyflavone) and luteolin (3′,4′,5,7-tetrahydroxyflavone) are important bioactive compounds with antioxidative, anti-allergic, and anti-inflammatory properties. However, both are unstable when exposed to atmospheric oxygen, which causes degradation and complicates their analytical determinations. The oxidative change of these flavonoids was observed and followed by UV–visible spectrophotometry, both in aqueous and ethanolic solutions. The distribution of the degradation products in aqueous media was monitored by LC–MS and LC–DAD analysis. The amounts of oxidative reaction products increase with the exposure time. The oxidative degradation reduces the pharmacological efficiency of these antioxidants and renders analytical determination inaccurate. The oxidative changes in flavonoid test solutions can explain the inconsistent dissociation constants reported in the literature. Dissociation constants of quercetin and luteolin were determined both by alkalimetric titration and by UV–visible spectrophotometry under deaerated conditions. The values pK1 = 5.87 ± 0.14 and pK2 = 8.48 ± 0.09 for quercetin, and pK1 = 5.99 ± 0.32 and pK2 = 8.40 ± 0.42 for luteolin were found. FigureThe change of absorption spectra of quercetin during the exposure to the air oxygen

On the difference in decomposition of taxifolin and luteolin vs. fisetin and quercetin in aqueous media

The decomposition of flavonols quercetin and fisetin, flavone luteolin and flavanone taxifolin was studied in slightly alkaline solution under ambient conditions. The study was based on spectrophotometry and high-pressure liquid chromatography. Products formed by atmospheric oxygen oxidation and hydrolysis were identified by HPLC–DAD and HPLC–ESI-MS/MS. Only small differences in the chemical structure of flavonoids resulted in extremely variable oxidation pathways and products. Oxidation of flavonols led to the formation of both a benzofuranone derivative and several open structures. On the contrary, the benzofuranone derivative was not found as a product of taxifolin and luteolin oxidative decomposition. These compounds were oxidized to their hydroxylated derivatives and typical open structures. Quercetin was not identified as a possible oxidation product of taxifolin.Graphical Abstract

Electrochemistry and spectroelectrochemistry of bioactive hydroxyquinolines: a mechanistic study.

The oxidation mechanism of selected hydroxyquinoline carboxylic acids such as 8-hydroxyquinoline-7-carboxylic acid (1), the two positional isomers 2-methyl-8-hydroxyquinoline-7-carboxylic acid (3) and 2-methyl-5-hydroxyquinoline-6-carboxylic acid (4), as well as other hydroxyquinolines were studied in aprotic environment using cyclic voltammetry, controlled potential electrolysis, in situ UV-vis and IR spectroelectrochemistry, and HPLC-MS/MS techniques. IR spectroelectrochemistry showed that oxidation unexpectedly proceeds together with protonation of the starting compound. We proved that the nitrogen atom in the heterocycle of hydroxyquinolines is protonated during the apparent 0.7 electron oxidation process. This was rationalized by the autodeprotonation reaction by another two starting molecules of hydroxyquinoline, so that the overall oxidation mechanism involves two electrons and three starting molecules. Both the electrochemical and spectroelectrochemical results showed that the oxidation mechanism is not influenced by the presence of the carboxylic group in the chemical structure of hydroxyquinolines, as results from oxidation of 2,7-dimethyl-5-hydroxyquinoline (6). In the presence of a strong proton acceptor such as pyridine, the oxidation ECEC process involves two electrons and two protons per one molecule of the hydroxyquinoline derivative. The electron transfer efficiency of hydroxyquinolines in biosystems may be related to protonation of biocompounds containing nitrogen bases. Molecular orbital calculations support the experimental findings.

Exploring the oxidation and iron binding profile of a cyclodextrin encapsulated quercetin complex unveiled a controlled complex dissociation through a chemical stimulus

BACKGROUND Flavonoids possess a rich polypharmacological profile and their biological role is linked to their oxidation state protecting DNA from oxidative stress damage. However, their bioavailability is hampered due to their poor aqueous solubility. This can be surpassed through encapsulation to supramolecular carriers as cyclodextrin (CD). A quercetin- 2HP-β-CD complex has been formerly reported by us. However, once the flavonoid is in its 2HP-β-CD encapsulated state its oxidation potential, its decomplexation mechanism, its potential to protect DNA damage from oxidative stress remained elusive. To unveil this, an array of biophysical techniques was used. METHODS The quercetin-2HP-β-CD complex was evaluated through solubility and dissolution experiments, electrochemical and spectroelectrochemical studies (Cyclic Voltammetry), UV-Vis spectroscopy, HPLC-ESI-MS/MS and HPLC-DAD, fluorescence spectroscopy, NMR Spectroscopy, theoretical calculations (density functional theory (DFT)) and biological evaluation of the protection offered against H2O2-induced DNA damage. RESULTS Encapsulation of quercetin inside the supramolecules cavity enhanced its solubility and retained its oxidation profile. Although the protective ability of the quercetin-2HP-β-CD complex against H2O2 was diminished, iron serves as a chemical stimulus to dissociate the complex and release quercetin. CONCLUSIONS We found that in a quercetin-2HP-β-CD inclusion complex quercetin retains its oxidation profile similarly to its native state, while iron can operate as a chemical stimulus to release quercetin from its host cavity. GENERAL SIGNIFICANCE The oxidation profile of a natural product once it is encapsulated in a supramolecular carrier was unveiled as also it was discovered that decomplexation can be triggered by a chemical stimilus.