A Dispersion Corrected DFT Investigation of the Inclusion Complexation of Dexamethasone with ß-Cyclodextrin and Molecular Docking Study of Its Potential Activity against COVID-19.

The encapsulation mode of dexamethasone (Dex) into the cavity of ß-cyclodextrin (ß-CD), as well as its potential as an inhibitor of the COVID-19 main protease, were investigated using density functional theory with the recent dispersion corrections D4 and molecular docking calculations. Independent gradient model and natural bond orbital approaches allowed for the characterization of the host-guest interactions in the studied systems. Structural and energetic computation results revealed that hydrogen bonds and van der Waals interactions played significant roles in the stabilization of the formed Dex@ß-CD complex. The complexation energy significantly decreased from -179.50 kJ/mol in the gas phase to -74.14 kJ/mol in the aqueous phase. A molecular docking study was performed to investigate the inhibitory activity of dexamethasone against the COVID-19 target protein (PDB ID: 6LU7). The dexamethasone showed potential therapeutic activity as a SARS CoV-2 main protease inhibitor due to its strong binding to the active sites of the protein target, with predicted free energy of binding values of -29.97 and -32.19 kJ/mol as calculated from AutoDock4 and AutoDock Vina, respectively. This study was intended to explore the potential use of the Dex@ß-CD complex in drug delivery to enhance dexamethasone dissolution, thus improving its bioavailability and reducing its side effects.

Inclusion complexation of chloroquine with α and β-cyclodextrin: Theoretical insights from the new B97-3c composite method

Inclusion complexes of α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) with chloroquine drug (CQ) have been explored using the recently developed B97-3c composite method. Calculated complexation energies were negatively higher for both CQ@α-CD and CQ@β-CD complexes indicating a thermodynamically favorable process. The inclusion mode involves the partial encapsulation of the fused aromatic ring of chloroquine in α- and β-CD cavities from the wider side, in agreement with proton NMR data. NCI-RDG, IGM and NBO analysis showed that weak Van der Waals intermolecular interactions and in particular strong intermolecular hydrogen bonding stabilize the inclusion of chloroquine that forms complex with β-CD more favorably than with α-CD.