Thermodynamics of Molecular Recognition of Bile Salts by 3,6'- (Oligoethylenediamino-Bridged) β-Cyclodextrin Dimers

The molecular recognition behaviors of some representative bile salts by three 3,6'-bridged β-cyclodextrin dimers with oligo(ethylenediamino) linkers in different lengths, i.e. 3,6'-(ethylenediamino-bridged) β-cyclodextrin dimer (1), 3,6'-(diethylenetriamino-bridged) β-cyclodextrin dimer (2), and 3,6'-(triethylenetetraamino-bridged) β-cyclodextrin dimer (3), were investigated in aqueous phosphate buffer solution (pH 7.20) at 25°C by means of 2D NMR spectroscopy and isothermal titration microcalorimetry. Owing to the cooperative host-linker-guest binding mode between host and guest, these 3,6'-bridged β-cyclodextrin dimers showed significantly enhanced binding abilities and molecular selectivities as compared with native β-cyclodextrin through the simultaneous contributions of hydrophobic, hydrogen bond, and electrostatic interactions. Thermodynamically, the inclusion complexations of these β-cyclodextrin dimers with bile salts were mainly driven by large enthalpic gain, accompanied by slight to moderate entropic loss. An enthalpy-entropy compensation analysis demonstrated that these β-cyclodextrin dimers experienced large conformational changes and extensive desolvation effect upon inclusion complexation with guest molecules.