Molecular electrostatic potentials and hydrogen bonding in alpha-, beta-, and gamma-cyclodextrins

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Carbohydrate Chemistry

Background:

• Cyclodextrins (CDs) are cyclic oligosaccharides with hydrophobic cavities capable of forming inclusion complexes with various guest molecules.
• Inclusion complex formation is primarily driven by electrostatic interactions between the host cyclodextrin and the guest molecule.
• Understanding the structural and electronic properties of CDs is crucial for designing effective host-guest systems.

Purpose of the Study:

• To investigate the electronic structure and molecular electrostatic potentials (MESP) of alpha-, beta-, and gamma-cyclodextrins (CDs).
• To elucidate the role of hydrogen bonding in determining the three-dimensional structure and cavity dimensions of CDs.
• To correlate MESP topography with the binding affinity and inclusion complex formation of CDs with guest molecules.

Main Methods:

• Utilized hybrid density functional theory (DFT) with the B3LYP functional to compute electronic structure and MESP.
• Analyzed the topography of MESP to understand hydrogen-bonded interactions involving primary and secondary hydroxyl groups.
• Correlated MESP features with the structural characteristics and cavity dimensions of different CD types.

Main Results:

• MESP topography accurately reflects cavity dimensions and hydrogen-bonding patterns in alpha-, beta-, and gamma-CDs.
• Hydrogen bonding between primary hydroxyl groups creates distinct cone-like (alpha-CD) or barrel-like (beta-, gamma-CD) structures.
• The strength of hydrogen bonding follows alpha-CD > beta-CD > gamma-CD for primary hydroxyls and the reverse for secondary hydroxyls.
• Weak hydrogen bonding in gamma-CD leads to shallower MESP minima, facilitating guest molecule penetration into the cavity.

Conclusions:

• The study provides insights into the structure-property relationships of cyclodextrins based on MESP analysis.
• Hydrogen bonding plays a critical role in defining the structural integrity and guest recognition capabilities of CDs.
• MESP topography serves as a valuable tool for predicting and understanding inclusion complex formation in cyclodextrin systems.