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 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.