Inclusion complex of 2-chlorobenzophenone with cyclomaltoheptaose (β-cyclodextrin): temperature, solvent effects and molecular modeling.

A thermodynamic study of the inclusion process between 2-chlorobenzophenone (2ClBP) and cyclomaltoheptaose (β-cyclodextrin, β-CD) was performed using UV-vis spectroscopy, reversed-phase liquid chromatography (RP-HPLC), and molecular modeling (PM6). Spectrophotometric measurements in aqueous solutions were performed at different temperatures. The stoichiometry of the complex is 1:1 and its apparent formation constant (K(c)) is 3846M(-1) at 30°C. Temperature dependence of K(c) values revealed that both enthalpy (ΔH°=-10.58kJ/mol) and entropy changes (ΔS°=33.76J/Kmol) are favorable for the inclusion process in an aqueous medium. Encapsulation was also investigated using RP-HPLC (C18 column) with different mobile-phase compositions, to which β-CD was added. The apparent formation constants in MeOH-H(2)O (K(F)) were dependent of the proportion of the mobile phase employed (50:50, 55:45, 60:40 and 65:35, v/v). The K(F) values were 419M(-1) (50% MeOH) and 166M(-1) (65% MeOH) at 30°C. The thermodynamic parameters of the complex in an aqueous MeOH medium indicated that this process is largely driven by enthalpy change (ΔH°=-27.25kJ/mol and ΔS°=-45.12J/Kmol). The results of the study carried out with the PM6 semiempirical method showed that the energetically most favorable structure for the formation of the complex is the 'head up' orientation.