title: Molecular recognition thermodynamics and structural elucidation of interactions between steroids and bridged bis(beta-cyclodextrin)s.
abstract: A series of bridged bis(beta-cyclodextrin(CD))s (2-7) were synthesized, i.e., bridged bis(beta-CD)s 2 and 3 bearing binaphthyl or biquinoline tethers and bridged bis(beta-CD)s 4-7 possessing dithiobis(benzoyl) tether, and their complex stability constants (KS), enthalpy (DeltaH degrees), and entropy changes (DeltaS degrees) for the 1:2 inclusion complexation with representative steroids, deoxycholate, cholate, glycocholate, and taurocholate, have been determined in an aqueous phosphate buffer solution of pH 7.20 at 298.15 K by means of titration microcalorimetry. The original conformations of bridged bis(beta-cyclodextrin)s were investigated by circular dichroism and 1H ROESY spectroscopy. Structures of the inclusion complexes between steroids and bridged bis(beta-CD)s in solution were elucidated by 2D NMR experiments, indicating that anionic groups of two steroid molecules penetrate, respectively, into the two hydrophobic CD cavities in one 6,6'-bridged bis(beta-CD) molecule from the secondary rim to give a 1:2 binding mode upon inclusion complexation. The results obtained from titration microcalorimetry and 2D NMR experiments jointly demonstrate that bridged bis(beta-CD)s 2, 3 and 5-7 tethered by protonated amino group possessing different substituted groups can enhance not only the molecular binding ability toward steroids by electrostatic interaction but also molecular selectivity. Thermodynamically, the resulting 1:2 bis(beta-CD)-steroid complexes are formed by an enthalpy-driven process, accompanied by smaller entropy loss. The increased complex stability mainly results from enthalpy gain, accompanied by large conformational change and extensive desolvation effects for the 1:2 inclusion complexation between bis(beta-CD)s and steroids.
authors.affiliation: Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. China. yuliu@public.tpt.tj.cn
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Ying-Wei
authors.initials: YW
authors.lastname: Yang
authors.forename: En-Cui
authors.initials: EC
authors.lastname: Yang
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Guan
mesh_terms: D008956:Models, Chemical; D015394:Molecular Structure; D013256:Steroids / Q000737:chemistry*; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D013256:Steroids; D047392:beta-Cyclodextrins