Strength from Weakness: Conformational Divergence between Solid and Solution States of Substituted Cyclitols Facilitated by CH···O Hydrogen Bonding

Abstract

We have investigated the conformational preferences of a series of cyclitol derivatives, namely mono- and diesters of 1,2:5,6-di-O-isopropylidene-myo-inositol and 1,2:5,6-di-O-cyclohexylidene-myo-inositol, in both solid and solution states. The solid-state conformations were determined by single-crystal X-ray analysis. The solution-state conformations were determined by using NMR. The experimental 3JHH values were applied in the Haasnoot–Altona equation to calculate the dihedral angle (ϕ) between the respective vicinal protons. By fixing the dihedral angle between different sets of vicinal protons, the molecules were energy-minimized by MM2 method to visualize their conformation in solution. As the solvent polarities can influence the conformational preference, we have determined the conformations of these molecules in various solvents of different polarities such as benzene-d6, chloroform-d, acetonitrile-d3, acetone-d6, methanol-d4, and DMSO-d6. All of the compounds adopted boat conformations in solution irrespective of the solvents, acyl groups, or alkylidene protecting groups. This conformation places H6 and O3 of the cyclitol ring in proximity, such that an intramolecular CH···O hydrogen bond between them stabilizes this otherwise unstable conformation. However, in the solid state, several intermolecular CH···O hydrogen bonds force these molecules to adopt the chair conformation. This study uncovers the role of weak noncovalent interactions in influencing the molecular conformations differentially in different states