Monatshefte für Chemie - Chemical Monthly

, Volume 149, Issue 10, pp 1739–1747 | Cite as

The inclusion complexation of daidzein with β-cyclodextrin and 2,6-dimethyl-β-cyclodextrin: a theoretical and experimental study

  • Thanyada RungrotmongkolEmail author
  • Tipsuda Chakcharoensap
  • Piamsook Pongsawasdi
  • Nawee Kungwan
  • Peter Wolschann
Original Paper


Daidzein is an isoflavone of the group of phytoestrogens extracted from soybeans and other legumes. As its structure is relatively similar to that of the hormone estrogen, daidzein is able to bind with estrogen receptors leading to a reduced postmenopausal women symptom. A common problem of the compounds of this group is the rather low water solubility with the consequence of limited pharmaceutical applications. Inclusion complexation between daidzein and two β-CDs (β-CD and DM-β-CD) was investigated by theoretical and experimental techniques. Based on multiple MD simulations in combination with different binding-free energy calculations, the most preferential mode of daidzein binding to cyclodextrins is the insertion of the chromone ring fitting well into the hydrophobic cavity. All four methods of binding-free energy calculations (MM/PBSA, MM/GBSA, QM/PBSA, and QM/GBSA) predict the binding affinity of the daidzein/DM-β-CD complex significantly higher than the daidzein/β-CD. Following the same trend, the experimental results also indicated the enhancement of solubility and stability of the daidzein/DM-β-CD complex. Moreover, it was found that the complexation process was favorably enthalpy driven.

Graphical abstract


Daidzein Cyclodextrin Inclusion complex Molecular dynamics simulation Phase solubility study 



This study was financially supported by the National Research University Project, Office of Higher Education Commission (WCU-023-FW-57). We also thank the Structural and Computational Biology Research Group, Special Task Force for Activating Research (STAR). N.K. would like to thank Center of Excellence in Materials Science and Technology, Chiang Mai University for the financial support. By travel grants for short research visit, research reported in this publication was also supported by the ASEAN-European Academic University Network (ASEA-UNINET). The Computational Chemistry Center of Excellent, and the Vienna Scientific Cluster (VSC-2) were acknowledged for facilities and computing resources.


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Thanyada Rungrotmongkol
    • 1
    • 2
    • 3
    Email author
  • Tipsuda Chakcharoensap
    • 1
  • Piamsook Pongsawasdi
    • 1
  • Nawee Kungwan
    • 4
    • 5
  • Peter Wolschann
    • 1
    • 6
    • 7
  1. 1.Structural and Computational Biology Research Group, Department of Biochemistry, Faculty of ScienceChulalongkorn UniversityBangkokThailand
  2. 2.Ph.D. Program in Bioinformatics and Computational Biology, Faculty of ScienceChulalongkorn UniversityBangkokThailand
  3. 3.Molecular Sensory Science Center, Faculty of ScienceChulalongkorn UniversityBangkokThailand
  4. 4.Department of Chemistry, Faculty of ScienceChiang Mai UniversityChiang MaiThailand
  5. 5.Center of Excellence in Materials Science and TechnologyChiang Mai UniversityChiang MaiThailand
  6. 6.Department of Pharmaceutical Technology and BiopharmaceuticsUniversity of ViennaViennaAustria
  7. 7.Institute of Theoretical ChemistryUniversity of ViennaViennaAustria

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