Molecular modeling study of structures, Hirschfield surface, NBO, AIM, RDG, IGM and 1HNMR of thymoquinone/hydroxypropyl-β-cyclodextrin inclusion complex from QM calculations.

• PM6-DH2 and DFT-D were applied to study thymoquinone@HPβ-CD. • Energies and thermodynamic parameters were calculated. • Chemical reactivity and hirshfeld surface have been investigated. • The nature of intermolecular interactions are understand by NBO, QTAIM, RDG-IGM analyses. In this work, the thymoquinone (TQ)/hydroxypropyl-β-cyclodextrin (HPβ-CD) inclusion complex has been investigated employing quantum mechanical calculations in gas phase and in water. Complexation energies, geometries parameters and thermodynamic parameters ΔH°, ΔS° and ΔG° have been investigated and analyzed. The results obtained clearly indicate that the complexation process with Orientation B (TQ enters into the cavity of HPβ-CD from its wide side by C2H6 group) is energetically favored than that of Orientation A (TQ penetrates the HPβ-CD cavity from its wide side by methyl group). Time-dependent (TD)-DFT analysis performed in water using polarizable continuum model (PCM) calculations reveal that the main absorption bands of thymoquinone arise from the π→π* transition, after encapsulated by hydroxypropyl-β-cyclodextrin to form inclusion complexes. (HOMO- LUMO) energy and global reactivity descriptor values were evaluated. The results of electrophilicity based charge transfer (ECT) indicate that, the charge transfer occurs from the host to the guest. The Hirschfield surface is also investigated. From QTAIM analysis, ∇2ρ(r) > 0 and H(r) > 0 at critical points for all intermolecular interactions correspond to weak H-bonds and affirm dominance of electrostatic interactions. Also, the ratio –G(r)/V(r) > 1 confirms the presence of weak hydrogen bonding and van der Waals interactions stabilizing the complex. In addition, the reduced density gradient (RDG) and the independent gradient model (IGM) methods were used to reveal and distinguish between attractive interactions such hydrogen bonds, repulsive interactions and van der Waals interactions. At last, 1H NMR chemical shifts were computed with gage-including atomic orbital (GIAO) and compared with experimental results. [ABSTRACT FROM AUTHOR]