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

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 complimentarity of host and guest are compatible. Further, interaction of guest molecules with the outer surface of α-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 α-, β-, and γ-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 α-CD, hydrogen-bonded interactions between primary −OH groups engender a "cone-like" structure, while in β- or γ-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 α-CD > β-CD > γ-CD, while the secondary hydrogen-bonded interactions exhibit a reverse trend. Thus weak hydrogen-bonded interactions prevalent in γ-CD manifest in shallow MESP minima near hydroxyl oxygens compared to those in α- or β-CD. Furthermore, electrostatic potential topography reveals that the guest molecule tends to penetrate inside the cavity forming the inclusion complex in β- or γ-CD.