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

Abstract 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.