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

Inclusion complexes of alpha-cyclodextrin (alpha-CD) and beta-cyclodextrin (beta-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@alpha-CD and CQ@alpha-CD complexes indicating a thermodynamically favorable process. The inclusion mode involves the partial encapsulation of the fused aromatic ring of chloroquine in alpha- and beta-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 beta-CD more favorably than with alpha-CD. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Inclusion complexes of chloroquine drug with alpha-cyclodextrin and beta-cyclodextrin have been studied using the B97-3c composite method, revealing a thermodynamically favorable process with stronger intermolecular hydrogen bonding stabilizing the inclusion of chloroquine with beta-CD.