Abstract
Genistein is an isoflavone with promising pharmaceutical applications. However, its low water solubility interferes with its potency, and therefore cyclodextrins (CDs) have been considered as possible drug delivery system (DDS). To investigate the complexation mechanism of genistein in cyclodextrin, we employed molecular dynamics (MD) simulations based on classical potentials and the density-functional tight-binding (DFTB) quantum chemical potential. Both classical and quantum chemical MD simulations predict that the phenol ring of genistein is preferentially complexed in the cavity of CD. The complexation process reduces the water-accessible solvation shell, and it is found that a hydrogen bond is formed between genistein and CD. The DFTB-based MD simulations reveal that spontaneous keto-enol tautomerization occurs even within a hundred picoseconds, which suggests that the encapsulated genistein is complexed in the ordinary enol form of the drug molecule. Analyses of the molecular charge distributions suggest that electrostatic interactions partially induce the complex formation, rather than extensive formation of hydrogen bonds.
Original language | English |
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Pages (from-to) | 16-23 |
Number of pages | 8 |
Journal | Journal of Molecular Liquids |
Volume | 265 |
DOIs | |
State | Published - Sep 1 2018 |
Externally published | Yes |
Funding
This study was supported by the Asia Research Center Fund, Chulalongkorn University (CU). C.H. thanks Science Achievement Scholarship of Thailand and Overseas Undergraduate Student Exchange Program, Faculty of Science, Mahidol University. We also thank the Structural and Computational Biology Research Group, Special Task Force for Activating Research (STAR), Faculty of Science, CU, and Thailand Research Fund ( IRG5780008 ). N.K. would like to thank Center of Excellence in Materials Science and Technology, Chiang Mai University for the financial support. T.R. thanks the Hitachi Global Foundation for research fellowship. 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 Center of Excellent in Computational Chemistry, and the Vienna Scientific Cluster (VSC-2) were acknowledged for facilities and computing resources. This study was supported by the Asia Research Center Fund, Chulalongkorn University (CU). C.H. thanks Science Achievement Scholarship of Thailand and Overseas Undergraduate Student Exchange Program, Faculty of Science, Mahidol University. We also thank the Structural and Computational Biology Research Group, Special Task Force for Activating Research (STAR), Faculty of Science, CU, and Thailand Research Fund (IRG5780008). N.K. would like to thank Center of Excellence in Materials Science and Technology, Chiang Mai University for the financial support. T.R. thanks the Hitachi Global Foundation for research fellowship. 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 Center of Excellent in Computational Chemistry, and the Vienna Scientific Cluster (VSC-2) were acknowledged for facilities and computing resources.
Keywords
- Density-functional tight-binding
- Genistein
- Inclusion complex
- Keto-enol tautomerization
- Molecular dynamics simulation
- Umbrella sampling
- β-Cyclodextrin