Host-guest molecular encapsulation of cucurbit[7]uril with dillapiole congeners using docking simulation and density functional theory approaches

Binding affinity and intermolecular interactions are essential characteristics that could be used to comprehend molecular recognition between molecules in supramolecular host-guest systems. This work presented a molecular docking simulation and density functional theory (DFT) calculation at the B3LYP-631g(d) level of theory on dillapiole and its derivatives (guest compounds) complexation with cucurbit[7]uril (host compound). The supramolecular host-guest inclusion complex binding energies, − 4.46 to − 5.47 kcal mol −1 and − 0.53 to − 15.38 kcal mol −1 for docking and DFT calculation, respectively, were calculated, and the intermolecular interactions such as the hydrogen bonding, electrostatic, dispersion, and pi-alkyl formation involved were observed. The negative binding energies of D1 -CB [7], D2 -CB [7], D3 -CB [7], D4 -CB [7], D5 -CB [7], D6 -CB [7], and D -CB [7], computed from both the theoretical approaches, suggested the possible inclusion of the guests inside the cucurbit[7]uril cavity, enabling the formation of stable inclusion compounds. However, the significant difference in the binding energy values from the DFT calculation demonstrated a clustered preference in terms of the complex stabilisation, with D2 -CB [7], D3 -CB [7], D5 -CB [7], and D6 -CB [7] dominantly favourable, while D1 -CB [7], D4 -CB [7], and D were inclusion complexes with the least favourable. Encapsulation of the guests’ structural frame as a whole or a part and steric constraint associated with the guests’ substituents positioning in addition to the intermolecular interactions were also noted to induce stabilisation in the binding energy, thus reflecting a preferable inclusion complex. Besides, the theoretical calculations on the rationalisation of the selected guests’ energy barrier were found to correlate well with experimental works of hydroboration oxidation synthesis to produce alcohol derivatives of dillapiole.