Demonstrating accuracy of the already proposed protocol for structure elucidation of cyclodextrin inclusion complexes by validation using quantitative ROESY analysis

In this study, we attempt to ascertain the accuracy of the structures determined using our previously developed method and hence the accuracy of our method. In the present report, we have taken the guest molecule cetirizine (CTZ) and the host molecules are α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD). Structures with good accuracy were elucidated using a productive fusion of experimental and computational methods. We performed molecular mechanics studies (MM) in light of experimental ROESY studies, followed by molecular dynamics studies (MD). The results from these studies were analyzed using quantitative ROESY analysis to determine the final accurate structures of the complexes. The accuracy of these structures was tested using density functional theory (DFT) that is an accurate method for structure determination. DFT studies were carried out using the functionals B3LYP and M06L with def-TZVP basis set and similarly quantitative ROESY analysis was performed for the obtained structures. The ROESY intensities of the structures obtained from MM and MD studies, were compared with ROESY intensities of the structures obtained from DFT studies. Calculated ROESY intensities of the structures obtained from B3LYP functional are comparable, with intensities of structures obtained from MM and MD studies, but M06L functional showed poor results. In addition to the accuracy of MM and MD studies, low computational cost and less time input make it good method for structural studies for CD inclusion complexes.