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Article

Comparative Interaction Studies of Quercetin with 2-Hydroxyl-propyl-β-cyclodextrin and 2,6-Methylated-β-cyclodextrin

1
Organic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopollis Zografou, 11571 Athens, Greece
2
Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou, 11527 Athens, Greece
3
Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
4
Slovenian NMR Centre, National Institute of Chemistry, SI-1001 Ljubljana, Slovenia
5
Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece
6
Institute of Materials Science and Computing, University Research Center of Ioannina (URCI), 45110 Ioannina, Greece
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Laboratory of Physical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
8
Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 11635 Athens, Greece
*
Authors to whom correspondence should be addressed.
Academic Editors: Angelina Angelova and Maria Emília de Sousa
Molecules 2022, 27(17), 5490; https://doi.org/10.3390/molecules27175490
Received: 6 July 2022 / Revised: 6 August 2022 / Accepted: 19 August 2022 / Published: 26 August 2022
Quercetin (QUE) is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility its bioavailability is limited. In the present study, we examine whether its formulation with two cyclodextrins (CDs) may enhance its pharmacological profile. Comparative interaction studies of quercetin with 2-hydroxyl-propyl-β-cyclodextrin (2HP-β-CD) and 2,6-methylated cyclodextrin (2,6Me-β-CD) were performed using NMR spectroscopy, DFT calculations, and in silico molecular dynamics (MD) simulations. Using T1 relaxation experiments and 2D DOSY it was illustrated that both cyclodextrin vehicles can host quercetin. Quantum mechanical calculations showed the formation of hydrogen bonds between QUE with 2HP-β-CD and 2,6Μe-β-CD. Six hydrogen bonds are formed ranging between 2 to 2.8 Å with 2HP-β-CD and four hydrogen bonds within 2.8 Å with 2,6Μe-β-CD. Calculations of absolute binding free energies show that quercetin binds favorably to both 2,6Me-β-CD and 2HP-β-CD. MM/GBSA results show equally favorable binding of quercetin in the two CDs. Fluorescence spectroscopy shows moderate binding of quercetin in 2HP-β-CD (520 M−1) and 2,6Me-β-CD (770 M−1). Thus, we propose that both formulations (2HP-β-CD:quercetin, 2,6Me-β-CD:quercetin) could be further explored and exploited as small molecule carriers in biological studies. View Full-Text
Keywords: quercetin; 2-hydroxyl-propyl-β-cyclodextrin; 2,6-methylated cyclodextrin; molecular interactions; NMR spectroscopy; molecular dynamics; absolute free energy calculation; FEP; fluorescence spectroscopy; Density Functional Theory (DFT) quercetin; 2-hydroxyl-propyl-β-cyclodextrin; 2,6-methylated cyclodextrin; molecular interactions; NMR spectroscopy; molecular dynamics; absolute free energy calculation; FEP; fluorescence spectroscopy; Density Functional Theory (DFT)
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MDPI and ACS Style

Vakali, V.; Papadourakis, M.; Georgiou, N.; Zoupanou, N.; Diamantis, D.A.; Javornik, U.; Papakyriakopoulou, P.; Plavec, J.; Valsami, G.; Tzakos, A.G.; Tzeli, D.; Cournia, Z.; Mauromoustakos, T. Comparative Interaction Studies of Quercetin with 2-Hydroxyl-propyl-β-cyclodextrin and 2,6-Methylated-β-cyclodextrin. Molecules 2022, 27, 5490. https://doi.org/10.3390/molecules27175490

AMA Style

Vakali V, Papadourakis M, Georgiou N, Zoupanou N, Diamantis DA, Javornik U, Papakyriakopoulou P, Plavec J, Valsami G, Tzakos AG, Tzeli D, Cournia Z, Mauromoustakos T. Comparative Interaction Studies of Quercetin with 2-Hydroxyl-propyl-β-cyclodextrin and 2,6-Methylated-β-cyclodextrin. Molecules. 2022; 27(17):5490. https://doi.org/10.3390/molecules27175490

Chicago/Turabian Style

Vakali, Vasiliki, Michail Papadourakis, Nikitas Georgiou, Nikoletta Zoupanou, Dimitrios A. Diamantis, Uroš Javornik, Paraskevi Papakyriakopoulou, Janez Plavec, Georgia Valsami, Andreas G. Tzakos, Demeter Tzeli, Zoe Cournia, and Thomas Mauromoustakos. 2022. "Comparative Interaction Studies of Quercetin with 2-Hydroxyl-propyl-β-cyclodextrin and 2,6-Methylated-β-cyclodextrin" Molecules 27, no. 17: 5490. https://doi.org/10.3390/molecules27175490

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