Molecular Recognition Thermodynamics of Steroids by Novel Oligo(aminoethylamino)-?-cyclodextrins Bearing Anthryl: Enhanced Molecular Binding Ability by Co-inclusion Complexation

Abstract

Three β-cyclodextrin (β-CD) derivatives bearing anthracene group (2–4) were synthesized by the condensation of 9-anthracenecarboxylic acid with the corresponding oligo(aminoethylamino)-β-CDs in 33–36% yields and their original conformations and binding behavior with steroid molecules were investigated by using spectroscopic techniques and isothermal calorimeter. The combination of induced circular dichroism (ICD) and 2D NMR spectra reveals that the anthryl group attached to β-CD is itself included in cavity and the chain length of oligo(aminoethylamino) decides the orientation of the anthryl located in the cavity to some extent, directly affecting the binding ability with guest molecules. Calorimetric titration has been performed at buffer aqueous solution (pH 7.2) at 25 °C to give the binding constants (K_S) and thermodynamic parameters for 11 inclusion complexation of modified β-CDs 2–4 and representative steroids, i.e., cholate, deoxycholate, glycocholate, and taurocholate. Possessing the sidearm with appropriate length, 3 gives the highest stability constant of 22485± 15 M−1 for the complexation with deoxycholate molecule, which may be ascribed to the co-inclusion interactions between the host and guest. As compared with parent β-CD 1 upon complexation with steroids, hosts 2–4 with different chain lengths enhanced the binding ability and significant molecular discrimination, which are discussed comparatively and globally from the viewpoint of thermodynamics. Furthermore, we establish the correlation between the conformation of the resulting complexes and the thermodynamic parameters obtained.