Kinetic and thermodynamic consequences of the substitution of SMe for OMe substituents of cryptophane hosts on the binding of neutral and cationic guests

Abstract

To investigate the origin of the high selectivity of cryptophane-E (1) towards Me₃NH⁺, Me₄N⁺, and CHCl₃, and particularly to discriminate the different contributions that stabilize the supramolecular complexes, we have synthesized the new cryptophane 2 bearing six MeS groups instead of MeO groups in 1. This led to a decrease of the negative charge density in the equatorial region of 2 without affecting notably the size of the molecular cavity. The binding properties of 1 and 2 towards the three guests were examined in solution and showed a slight decrease of the ΔG_a favoring the complexes of 1, accompanied by a significant modification of the ΔH_avs. ΔS_a balance. The binding of the ammonium guests to 1 and 2 was strongly entropy driven, while that of CHCl₃ was purely enthalpy driven. A combination of spectroscopic and computational techniques was used to assign the main intermolecular interactions that occurred during the inclusion process. The neutral CHCl₃ molecule is more stabilized in the less negatively charged CTV cap of 1. The different behavior towards the ammonium cations can be explained in term of interactions with the electronegative heteroatoms and cation–π interactions. Moreover, this study revealed a considerable slowing down of the guest exchange kinetics with host 2, for which the association and dissociation rates are reduced by a factor 10³ to 10⁴ with respect to 1. For example, at room temperature, the Me₄N⁺@2 complex exhibits a half-life of ca. 2 years, instead of a few hours for the corresponding complex of 1.