LAUSR

Using quantum chemistry, we modeled the docking process of flavanone Naringenin guest molecule (Narg) in the host β-Cyclodextrin (β-CD) and also in modified heptakis(2,6-di-O-methyl)-β-CD (DIMEB). The effect of host methylation on the complexation behavior was highlighted through structural, electronic and nuclear studies. All ONIOM2 combinations of PM3 with B3LYP, M06-2X and wB97X-D methods at 6-31G (d) basis set, agree on the inclusion mode and the optimum 3D structure. We found a deep insertion of the hydroxy phenyl ring in the hydrophobic cavity of both hosts. On the other hand, only a partial inclusion of the hydroxy chromanone moiety, located nearby the primary rim in Narg/DIMEB complex 1 and the secondary rim in Narg/DIMEB complex 2 was found. Ground state calculations show that complex 1 is more stable than complex 2, which corroborates well with experimental results. We investigated Frontier Molecular Orbitals and global reactivity descriptors and we identified the interaction sites, the nature and the strength of intermolecular interactions using 1H NMR GIAO (Gauge-Including Atomic Orbital) method, Natural Bond Orbital (NBO) and Quantum Theory of Atom In Molecule (QTAIM) analysis. Particularly, the multifaceted nature of H-bonding interaction has been explained with QTAIM topological model which revealed the stabilization via the closed-shell interactions: C–H…H and O–H…O for both complexes, O–H…H and C–H…C for Narg/β-CD and Narg/DIMEB, respectively. QTAIM topological properties correlate well with the structural geometry and interactions predicted by both GIAO NMR and NBO analysis.