Characterization of Inclusion Interaction between Acylsulfonamide and β-Cyclodextrin: Experimentally and Molecular Modeling Studies

The inclusion complex of acylsulfonamide (ASL) with β-cyclodextrin (β-CD) was explored experimentally and by molecular modeling studies. The stoichiometric ratio of the complex was found to be 1 : 1 and the stability constant was evaluated using the Benesi–Hildebrand equation. Estimation of the thermodynamic parameters of the inclusion complex in vacuum demonstrates that it is an enthalpy driven process phase and an enthalpy–entropy simultaneous process in aqueous solution, which is consistent with the experimental results. Semi-empirical calculations using PM6 and ONIOM2 methods, in vacuum and in water, were undertaken and done. The energetically more favorable structure obtained with the ONIOM2 method leads to the rise of intermolecular hydrogen bonds between acylsulfonamide and β-cyclodextrin. These interactions were probed using the natural bond orbital (NBO).