Host-guest complex of nabumetone: β-cyclodextrin: quantum chemical study and QTAIM analysis

The aim of the present work is the investigation of the inclusion complex of nabumetone (NAB) and beta-cyclodextrin (beta-CD) using PM3, DFT, DFT-D and ONIOM2 methods. The results indicate that the most energetically favorable structure predicts a preference of the methoxy group to enter the cavity of beta-CD from its wide rim. Consequently, the butanone moiety is positioned outside the cavity on the side of the secondary hydroxyls, with a total insertion of naphthalene group. The semi-empirical PM3 results are in good agreement with those obtained by the DFT optimization (with and without dispersion correction). The donor-acceptor interactions between drug and the cavity wall of the host, studied on the basis of natural bonding orbital (NBO) analysis, show the presence of weak intermolecular hydrogen bonds in addition to the most important van der Waals interactions. Furthermore, it is revealed that among the DFT and DFT-D techniques selected to quantify these interactions, WB97X-D functional provides the greatest values of stabilization energies E-(2). Finally, a detailed topological charge density analysis based on the quantum theory of atoms in molecules (QTAIM), developed by Bader and co-workers, has been accomplished using the WB97X-D and B3LYP methods on the most favorable complexes. A good correlation between the structural parameters and the electronic density is found.