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

• Published in: Journal of molecular structure 2019-01, Vol.1176, p.461-469
• Main Authors: Ali, Syed Mashhood, Muzaffar, Sughra
• Format: Article
• Language: English
• Subjects: 1H NMR; Benzydamine hydrochloride; Molecular dynamics; Quantitative ROESY; β-Cyclodextrin
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2018.08.086

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. [Display omitted] •Atom accurate structures of β-CD/BZY complexes were determined by 1H NMR, 2D NMR and molecular modeling studies.•Molecular modeling studies provided detailed insights into the structures of the ensembles.•Quantitative ROESY method used to analyse the least energy computational models was in agreement with experimental data.