Validating strategy of quantitative ROESY analysis for structure determination of cyclodextrin inclusion complexes

Abstract

Highly atom accurate structures of the inclusion complexes between benzydamine hydrochloride (BZY) and β-Cyclodextrin (β-CD) were determined by a method using quantitative ROESY analysis of computational models. Intermolecular contacts were examined in the ROESY spectrum that provided details of the portions of BZY encapsulated in the cavity and the probable mode of entry. Molecular docking studies presented negative binding energies which proved spontaneous complexation between β-CD and BZY and displayed two different modes of binding. Molecular mechanics (MM) studies were performed for both rings, in different orientations and from both cavity ends, to gauge their inclusion depth and mode of entry. Molecular dynamics (MD) studies were carried out to visualise the complexation process. Large number of minimum energy conformations from the MD runs were analysed by comparing their calculated intensities with experimental ROESY cross peak intensities to get the most probable structures of the ensembles.