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Type: Journal article
Title: Molecular basis of binding and stability of curcumin in diamide-linked y-cyclodextrin dimers
Author: Wallace, S.
Kee, T.
Huang, D.
Citation: The Journal of Physical Chemistry B: Biophysical Chemistry, Biomaterials, Liquids, and Soft Matter, 2013; 117(41):12375-12382
Publisher: Amer Chemical Soc
Issue Date: 2013
ISSN: 1520-6106
Statement of
Samuel J. Wallace, Tak W. Kee, and David M. Huang
Abstract: Curcumin is a naturally occurring molecule with medicinal properties that is unstable in water, whose efficacy as a drug can potentially be enhanced by encapsulation inside a host molecule. In this work, the thermodynamics and mechanism of binding of curcumin to succinamide- and urea-linked γ-cyclodextrin (γ-CD) dimers in water are investigated by molecular dynamics simulations. The simulated binding constants of curcumin to succinamide- and urea-linked γ-CD dimers at 310 K are 11.3 × 10⁶ M ⁻¹ and 1.6 × 10⁶ M ⁻¹, respectively, matching well with previous experimental results of 8.7 × 10⁶ M ⁻¹ and 2.0 × 10⁶ M ⁻¹. The simulations reveal structural information about the encapsulation of curcumin inside the diamide-linked γ-CD dimers, with distinct qualitative differences observed for the two dimers. In particular, (1) the predominant orientation of curcumin inside the urea-linked γ-CD dimer is perpendicular to that in the succinamide-linked γ-CD dimer; (2) the magnitude of the angle between the planes of the cyclodextrins is larger for the succinamide-linked γ-CD dimer; and (3) curcumin exhibits greater configurational freedom inside the urea-linked γ-CD dimer. A consequence of some of these structural differences is that the dimer interior is more accessible to water in the succinamide-linked γ-CD dimer. These observations explain the higher stability and lower binding constant observed experimentally for curcumin in the urea-linked cyclodextrin γ-CD dimer compared with the succinamide-linked γ-CD dimer. More generally, the results demonstrate how stability and binding strength can be decoupled and thus separately optimized in host–guest systems used for drug delivery.
Keywords: Diamide
Binding Sites
Molecular Structure
Models, Molecular
Rights: Copyright © 2013 American Chemical Society
DOI: 10.1021/jp406125x
Appears in Collections:Aurora harvest
Chemistry and Physics publications

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