Comparative Interaction Studies of Quercetin with 2-Hydroxyl-propyl-β-cyclodextrin and 2,6-Methylated-β-cyclodextrin
Vasiliki Vakali,
Michail Papadourakis,
Nikitas Georgiou,
Nikoletta Zoupanou,
Dimitrios A. Diamantis,
Uroš Javornik,
Paraskevi Papakyriakopoulou,
Janez Plavec,
Georgia Valsami,
Andreas G. Tzakos,
Demeter Tzeli,
Zoe Cournia,
Thomas Mauromoustakos
Affiliations
Vasiliki Vakali
Organic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopollis Zografou, 11571 Athens, Greece
Michail Papadourakis
Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou, 11527 Athens, Greece
Nikitas Georgiou
Organic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopollis Zografou, 11571 Athens, Greece
Nikoletta Zoupanou
Organic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopollis Zografou, 11571 Athens, Greece
Dimitrios A. Diamantis
Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
Uroš Javornik
Slovenian NMR Centre, National Institute of Chemistry, SI-1001 Ljubljana, Slovenia
Paraskevi Papakyriakopoulou
Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece
Janez Plavec
Slovenian NMR Centre, National Institute of Chemistry, SI-1001 Ljubljana, Slovenia
Georgia Valsami
Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece
Andreas G. Tzakos
Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioannina, Greece
Demeter Tzeli
Laboratory of Physical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
Zoe Cournia
Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou, 11527 Athens, Greece
Thomas Mauromoustakos
Organic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopollis Zografou, 11571 Athens, Greece
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.
