Structures and stabilities of naturally occurring cyclodextrins: a theoretical study of symmetrical conformers.

A molecular modeling study of symmetrical conformers of α-, β-, and γ-cyclodextrins in the gas and aqueous phases was carried out using the M06-2X density functional method, with SMD employed as an implicit solvation model. Eight symmetrical conformers were found for each cyclodextrin. Values of geometrical parameters obtained from the modeling study were found to agree well with those obtained from X-ray diffraction structures. A vibrational analysis using harmonic frequencies was performed to determine thermodynamic quantities. The GIAO method was applied to determine proton and carbon-13 NMR chemical shifts, which were then compared with corresponding chemical shifts reported in the literature. Hydrogen-bonding patterns were analyzed using geometrical descriptors, and quantum chemical topology was explored by QTAIM analysis. The results of this study indicated that four of the eight conformers studied for each cyclodextrin are the most populated in aqueous solution. These results provide the foundations for future studies of host-guest complexes involving these cyclodextrins. Graphical abstract δΔGsolvation: variation of free Gibss energy of solvation.