Molecular Electrostatic Potentials and Hydrogen Bonding in α-, β-, and γ-Cyclodextrins

Abstract

Cyclodextrins (CDs) are cyclic oligomers of glucose having the toroid of sugars elaborating a central cavity of varying size depending on the number of glucoses. The central hydrophobic cavity of CD shows a binding affinity toward different guest molecules, which include small substituted benzenes to long chain surfactant molecules leading to a variety of inclusion complexes when the size and shape complementarity of host and guest are compatible. Further, interaction of guest molecules with the outer surface of alpha-CD has also been observed. Primarily it is the electrostatic interactions that essentially constitute a driving force for the formation of inclusion complexes. To gain insights for these interactions, the electronic structure and the molecular electrostatic potentials in alpha-, beta-, and gamma-CDs are derived using the hybrid density functional theory employing the three-parameter exchange correlation functional due to Becke, Lee, Yang, and Parr (B3LYP). The present work demonstrates how the topography of the molecular electrostatic potential (MESP) provides a measure of the cavity dimensions and understanding of the hydrogen-bonded interactions involving primary and secondary hydroxyl groups. In alpha-CD, hydrogen-bonded interactions between primary -OH groups engender a "cone-like" structure, while in beta- or gamma-CD the interactions from the primary -OH with ether oxygen in glucose ring facilitates a "barrel-like" structure. Further, the strength of hydrogen-bonded interactions of primary -OH groups follows the rank order alpha-CD > beta-CD > gamma-CD, while the secondary hydrogen-bonded interactions exhibit a reverse trend. Thus weak hydrogen-bonded interactions prevalent in gamma-CD manifest in shallow MESP minima near hydroxyl oxygens compared to those in alpha- or beta-CD. Furthermore, electrostatic potential topography reveals that the guest molecule tends to penetrate inside the cavity forming the inclusion complex in beta- or gamma-CD.

Influence of intramolecular hydrogen bonds on the binding potential of methylated β-cyclodextrin derivatives

“…Hydrogen bonds between primary hydroxy groups were only found for α-CD, leading to a conical host conformation, which is unfavorable for the accommodation of a guest [45]. Therefore, methylation at the primary positions should not significantly diminish the rigidity of the CD torus.…”

A Study of the Behavior of α-Cyclodextrin with Single Solutions of Hydrogenated and Fluorinated Surfactants and Their Mixtures

“…This extracavity association is attributed to the interactions between the CF 3 groups and the hydroxyl groups at the R-CD annulus. It has been shown in the literature that R-CD favors the formation of a "conelike" structure rather than a "barrel-like" structure as in -or γ-CD, 21 which might enable the weak association between SPFO and R-CD.…”

Modeling the effects of cyclodextrin on intracellular membrane vesicles from Cos-7 cells prepared by sonication and carbonate treatment

“…In this study we investigated the relationship between membrane composition, density, and size by using methyl- β -cyclodextrin (cyclodextrin) to rapidly deplete membrane cholesterol from an isolated intracellular membrane preparation. Cyclodextrins are a family of cyclic oligosaccharides that adopt a cone-like structure in aqueous solution, with an internal hydrophobic core that can sequester lipids from membranes ( Heine et al, 2007 ; Pinjari, Joshi & Gejji, 2006 ). Cyclodextrins have useful pharmaceutical applications as soluble carriers for hydrophobic molecules and are also commonly used in biochemical and cell biology studies to manipulate membrane lipid levels ( Loftsson & Brewster, 1996 ; Rodal et al, 1999 ; Welliver, 2006 ; Zidovetzki & Levitan, 2007 ).…”