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

Abstract

The molecular recognition behaviors of some representative bile salts by three 3,6'-bridged beta-cyclodextrin dimers with oligo(ethylenediamino) linkers in different lengths, i.e. 3,6'-(ethylenediamino-bridged) beta-cyclodextrin dimer (1), 3,6'-(diethylenetriamino-bridged) beta-cyclodextrin dimer (2), and 3,6'-(triethylenetetraamino-bridged) beta-cyclodextrin dimer (3), were investigated in aqueous phosphate buffer solution (pH 7.20) at 25 degrees 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 beta-cyclodextrin dimers showed significantly enhanced binding abilities and molecular selectivities as compared with native beta-cyclodextrin through the simultaneous contributions of hydrophobic, hydrogen bond, and electrostatic interactions. Thermodynamically, the inclusion complexations of these beta-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 beta-cyclodextrin dimers experienced large conformational changes and extensive desolvation effect upon inclusion complexation with guest molecules.

Thermodynamic Study of Cyclodextrins Complexation with Benzimidazolic Antihelmintics in Different Reaction Media

“…To verify the formation of the inclusion compound and to establish the guest location into the cyclodextrin, bidimensional 1 H NMR spectroscopy was employed [40,41] to get structural information about the 1:1 inclusion complex, when the solubility of the inclusion complex allowed using this technique (only for mebendazole and thiabendazole in DMSO-d 6 ). Mebendazole NMR spectra had been previously reported [25].…”

Thermodynamics of Resulting Complexes Between Cyclodextrins and Bile Salts

“…1:1 binding stoichiometry is observed for all the complexes between bile salts and oligoethylenediamino-bridged -CDs (42-44) [29]. The inclusion complexation of bile salts with 42-44 is driven by favorable enthalpy changes, accompanied by slight to moderate entropy loss.…”

“…The stability constants of the complexes formed by -CD dimers 42-44 with bile salts are larger than those of the complexes formed by native -CD 1 [29]. These enhanced binding abilities of -CD dimers may be mainly attributed to the cooperative host-linker-guest binding mode between host and guest.…”

“…Therefore, DCA gives the highest binding abilities among the bile salts examined upon complexation with most CDs [29]. Possess more polar side-chains, GCA and TCA show weak binding abilities upon inclusion complexation complexation with -CD dimers due to the relatively poor hydrophobic interactions between host and guest.…”

“…To obtain the information about the binding modes between bile salts and oligoethylenediamino-bridged -CD dimers (42-44), 2D ROESY spectra for typical hostguest pairs have been determined by Liu et al [29]. The results of ROESY experiments indicated that the D ring and side-chain of bile salt guest enter one -CD cavity from the wide opening, and the linker group is partially self-included in the other -CD cavity (Figure 8).…”