View article

The complex formation between daclatasvir and γ-CD or heptakis(2,3,6-tri-O-methyl)-β-CD (TM-β-CD) was studied by isothermal titration calorimetry and molecular modeling. Both techniques supported the predominant formation of a 2:1 complex in case of γ-CD although a 1:1 complex may be formed to a much lower extent as well. In case of TM-β-CD the stoichiometry of the complex was exclusively 1:1. Complex formation with γ-CD did not require dissociation of the daclatasvir dimer, which is present in solution, and resulted in a complex with a binding constant of 1.67·10⁷ M⁻². In contrast, formation of the weak TM-β-CD complex (K = 371 M⁻¹) required dissociation of the daclatasvir dimer. This is in line with the observation that the complex formation in case of γ-CD is enthalpy-driven, while the process is entropy-driven in case of TM-β-CD. It is concluded that the plateau observed in capillary electrophoresis is …