Molecular recognition thermodynamics and structural elucidation of interactions between steroids and bridged bis(β-cyclodextrin)s

Yu Liu, Ying Wei Yang, En Cui Yang, Xu Dong Guan

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A series of bridged bis(β-cyclodextrin(CD))s (2-7) were synthesized, i.e., bridged bis(β-CD)s 2 and 3 bearing binaphthyl or biquinoline tethers and bridged bis(β-CD)s 4-7 possessing dithiobis(benzoyl) tether, and their complex stability constants (KS), enthalpy (ΔH°), and entropy changes (ΔS°) 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(β-cyclodextrin)s were investigated by circular dichroism and 1H ROESY spectroscopy. Structures of the inclusion complexes between steroids and bridged bis(β-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(β-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(β-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(β-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(β-CD)s and steroids.

Original languageEnglish (US)
Pages (from-to)6590-6602
Number of pages13
JournalJournal of Organic Chemistry
Issue number20
StatePublished - Oct 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry


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