Molecular Recognition Thermodynamics and Structural Elucidation of Interactions between Steroids and Bridged Bis(β-cyclodextrin)s

• Published in: Journal of organic chemistry 2004-10, Vol.69 (20), p.6590-6602
• Main Authors: Liu, Yu, Yang, Ying-Wei, Yang, En-Cui, Guan, Xu-Dong
• Format: Article
• Language: English
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; beta-Cyclodextrins - chemical synthesis; beta-Cyclodextrins - chemistry; Chemistry; Coordination compounds; Exact sciences and technology; Inorganic chemistry and origins of life; Models, Chemical; Molecular Structure; Organic chemistry; Preparations and properties; Steroids; Steroids - chemistry; Thermodynamics
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo049143k

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 (K S), 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.