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. 2020 Jan 24;21(3):766.
doi: 10.3390/ijms21030766.

Solubility Enhancement of Myricetin by Inclusion Complexation with Heptakis- O-(2-Hydroxypropyl)-β-Cyclodextrin: A Joint Experimental and Theoretical Study

Dongxu Han  1 , Zhongbao Han  1 , Liyan Liu  1 , Ying Wang  1 , Shigang Xin  2 , Hongbo Zhang  2 , Zhan Yu  1
Affiliations

Solubility Enhancement of Myricetin by Inclusion Complexation with Heptakis- O-(2-Hydroxypropyl)-β-Cyclodextrin: A Joint Experimental and Theoretical Study

Dongxu Han et al. Int J Mol Sci. .

Abstract

Four cyclodextrins (CD) including β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), heptakis-O-(2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), and heptakis-O-(2, 6-di-O-methyl)-β-cyclodextrin (DM-β-CD) were used as solubilizer to study the solubility enhancement of myricetin. The results of the phase solubility study showed that the presence of CDs could enhance the solubility of myricetin by forming 1:1 complexes. Among all CDs, HP-β-CD had the highest solubilization effect to myricetin. The concentration of myricetin could be 1.60 × 10-4 moL/L when the presence of HP-β-CD reached 1.00 × 10-2 moL/L, which was 31.45 times higher than myricetin's aqueous solubility. Subsequently, the HP-β-CD:myricetin complex was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). In order to get an insight of the plausible structure of the complex, molecular docking was used to study the complexation process of HP-β-CD and myricetin. In the complex, the A ring and C ring of myricetin were complexed into the hydrophobic cavity of HP-β-CD, while the ring B was located at the wide rim of HP-β-CD. Four hydrogen bonding interactions were found between HP-β-CD and -OH groups of the guest in the HP-β-CD: myricetin complex. The complexation energy (△E) for the host-guest interactions was calculated with a negative sign, indicating the formation of the complex was an exergonic process. A 30-ns molecular dynamics simulation was conducted to the HP-β-CD: myricetin complex. Calculation results showed that no large structural deformation or position change were observed during the whole simulation time span. The average root-mean-square deviation (RMSD) changes of the host and guest were 2.444 and 1.145 Å, respectively, indicating the complex had excellent stability.

Keywords: HP-β-CD; Keywords myricetin; PM6-D3H4; PM7; molecular dynamics; phase solubility.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Chemical structures of cyclodextrins (CDs) (A) and myricetin (B). Abbreviations: β-cyclodextrin, (β-CD); γ-cyclodextrin, (γ-CD); heptakis-O-(2-hydroxypropyl)-β-cyclodextrin, (HP-β-CD); and heptakis-O-(2, 6-di-O-methyl)-β-cyclodextrin, (DM-β-CD).
Figure 2
Figure 2
Phase solubility diagrams of myricetin in aqueous solution with the presence of various CDs.
Figure 3
Figure 3
Fourier transform infrared spectroscopy (FT-IR) spectra of HP-β-CD: myricetin inclusion complex (a), HP-β-CD: myricetin physical mixture (b), HP-β-CD (c) and myricetin (d).
Figure 4
Figure 4
X-ray diffraction (XRD) patterns of HP-β-CD: myricetin inclusion complex (a), HP-β-CD: myricetin physical mixture (b), myricetin (c), and HP-β-CD (d).
Figure 5
Figure 5
TG (A) and DTG (B) curves of HP-β-CD: myricetin inclusion complex (a), HP-β-CD: myricetin physical mixture (b), myricetin (c) and HP-β-CD (d).
Figure 6
Figure 6
Snapshot of the lowest energy docking result for CD: myricetin complexes, where CD is β-CD (A), γ-CD (B) DM-β-CD (C), or HP-β-CD (D). Hydrogen bonds are dashed lines with indicated distances (in Å).
Figure 7
Figure 7
Root-mean-square deviation (RMSD) plots of all atoms for HP-β-CD: myricetin complex.
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References

    1. Saenger W. Cyclodextrin inclusion compounds in research and industry. Angew. Chem. Int. Ed. 1980;19:344–362. doi: 10.1002/anie.198003441. - DOI
    1. Singh R., Bharti N., Madan J., Hiremath S. Characterization of cyclodextrin inclusion complexes—A review. J. Pharm. Sci. Technol. 2010;2:171–183.
    1. Szejtli J. Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 1998;98:1743–1754. doi: 10.1021/cr970022c. - DOI - PubMed
    1. Swaminathan S., Pastero L., Serpe L., Trotta F., Vavia P., Aquilano D., Trotta M., Zara G., Cavalli R. Cyclodextrin-based nanosponges encapsulating camptothecin: Physicochemical characterization, stability and cytotoxicity. Eur. J. Pharm. Biopharm. 2010;74:193–201. doi: 10.1016/j.ejpb.2009.11.003. - DOI - PubMed
    1. Wang J., Cao Y., Sun B., Wang C. Physicochemical and release characterisation of garlic oil-β-cyclodextrin inclusion complexes. Food Chem. 2011;127:1680–1685. doi: 10.1016/j.foodchem.2011.02.036. - DOI

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