Selective Binding Thermodynamics of Bile Acids by Oligo (ethylenediamino)-β-Cyclodextrins and Their Copper (II) Complexes

Abstract

Complex stability constants (KS), standard molar enthalpy changes (DH) and entropy changes (TDS) for the inclusion complexation of native b-cyclodextrin (b-CD) (1) and some modified b-CDs, i.e., mono(6-ethylenediamino-6-deoxy)-b-CD (3), mono[6-diethylenetriamino-6-deoxy]-b-CD (4) and their corresponding copper complexes 5 and 6, with four representative bile acid guests, i.e., cholate (CA), deoxycholate (DCA), glycocholate (GCA) and taurocholate (TCA), were determined at 25 C in aqueous phosphate buffer solution (pH 7.20) by means of isothermal titration microcalorimetry (ITC). The stoichiometry of resulting inclusion complexes between CDs and bile acids was demonstrated by UV and conductivity as well as ITC experiments, showing 1:1 binding model upon all inclusion complexation except for metal-mediated dimer 5. The complex stability constants for modified b-CD 2-4 are dramatically magnified with the extended length of amino tether. As compared with 3 and 4, copper(II) complexes 5 and 6 significantly enhance not only binding ability but also molecular selectivity toward bile guest molecule CA through multipoint recognition, but decreased complexes stability toward TCA could be attributed to the decreased hydrophobic microenvironment of CDs cavity due to the introduction of copper(II) coordination center. Thermodynamically, the resulting complexes between hosts and bile guests are driven absolutely by enthalpy, accompanied by entropy gain or loss. Using the present data and those previously reported for mono(6-amino-6-deoxy)-b-CD (2), thermodynamic behavior and enhanced molecular selectivity could be discussed from the viewpoint of hydrophobic interactions, electrostatic cooperation and van der Waals between the hosts and guests.