Quantum chemical investigations on hydrogen bonding interactions established in the inclusion complex β-cyclodextrin/benzocaine through the DFT, AIM and NBO approaches

Structure and stability of an inclusion complex formed by Benzocaine (BZC) and beta-cyclodextrin (beta-CD) were investigated computationally using different levels of theory. The conformational research based on PM6 method allowed reach two minimum-energy structures: model A and model B. The lowest conformers have been exposed to fully geometry optimization employing four DFT functionals: B3LYP, CAM-B3LYP, M05-2X and M06-2X. The performed DFT calculations have identified the model B, in which the amino group is located at the primary face of beta-CD, as the most stable complex by an amount up to -40 kcal/mol. Further, the greater stabilization of model B in respect to model A, has been ascertained through AIM and NBO analyses which clarified the main hydrogen bonds HBs interactions governing the reactivity of BZC inside the hydrophobic cavity of beta-CD. Finally, the estimated isotropic H-1 nuclear magnetic shielding constants generated from the gauge-including-atomic-orbital calculation have been analyzed and then compared with the available experimental data.