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

• Published in: Biochimica et biophysica acta Vol. 1862; no. 9; pp. 1913 - 1924
• Main Authors: Diamantis, Dimitrios A., Ramesova, Sarka, Chatzigiannis, Christos M., Degano, Ilaria, Gerogianni, Paraskevi S., Karadima, Konstantina E., Perikleous, Sonia, Rekkas, Dimitrios, Gerothanassis, Ioannis P., Galaris, Dimitrios, Mavromoustakos, Thomas, Valsami, Georgia, Sokolova, Romana, Tzakos, Andreas G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2018
• Subjects: Antioxidants; bioavailability; cyclodextrins; density functional theory; dissociation; DNA; DNA damage; DNA protection; electrochemistry; encapsulation; fluorescence emission spectroscopy; high performance liquid chromatography; hydrogen peroxide; iron; Metal complexes; nuclear magnetic resonance spectroscopy; oxidation; Oxidation mechanism; oxidative stress; Quercetin; solubility; Spectroelectrochemistry; ultraviolet-visible spectroscopy; Antioxidants; Que; CD; NMR; UV–Vis; Oxidation mechanism; Quercetin; 2HP-β-CD; DNA protection; Metal complexes; Spectroelectrochemistry
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2018.06.006

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. 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. Encapsulation of quercetin inside the supramolecule's 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. 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. 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. •In-depth exploration of quercetin-2HP-β-CD complex•Electrochemical oxidation profile of quercetin inside the cavity of 2HP-β-CD•Iron triggers the decomplexation of quercetin from the cavity of 2HP-β-CD.•DNA protection against oxidative stress induced from H2O2 by quercetin -2HP-β-CD.