Comparative study of complexation between cyclodextrins and xylazine using 1H NMR and molecular modelling methods

Abstract

Structure determination of the inclusion complexes of Xylazine (XYL) as the guest molecule with α-, HP-β- and γ-cyclodextrins (CDs) as host molecules was taken up, along with structural comparison between the inclusion complexes formed in each case. On the basis of our previous studies, a method comprising of experimental studies integrated with computational approach including molecular mechanics (MM) studies and molecular dynamics (MD) studies, was employed which provided exact structure of the inclusion complexes. 2D ROESY interactions were studied in each case, which confirmed formation of the inclusion complexes and showed parts of the guest encapsulated in the cavity. Only aromatic protons of XYL displayed interactions, which signified inclusion of the aromatic ring in the cavity in all the complexes. Considering the ROESY contacts, MM studies were performed for both the wide as well as narrow ends of the cavity for the three inclusion complexes. Further, to complement these structures, MD studies were performed for the inclusion complexes formed in each case. Several MD simulations were performed with different relative positions of the host and guest that determined structures of the ensembles consistent with the ROESY studies. This study has demonstrated the application of this method in the accurate structure establishment of the inclusion complexes.