STEROID COMPLEXATION BY CYCLOPHANE RECEPTORS IN AQUEOUS-SOLUTION - SUBSTRATE SELECTIVITY, ENTHALPIC DRIVING-FORCE FOR CAVITY INCLUSION, AND ENTHALPY-ENTROPY COMPENSATION

The synthesis, characterization, and steroid binding properties of two novel cyclophane receptors shaped by two naphthylphenylmethane spacers are reported. Cyclophane 1 forms inclusion complexes with bile acids, corticoids, and androgenic steroids in D2O/CD3OD 1:1. Specific functional group solvation effects generate high binding selectivity in the series of structurally similar bile acid derivatives: the complex of lithocholic acid is approximate to 2 kcal/mol more stable than the complex of deoxycholic acid. Steroid complexation by I is enthalpically driven, and complexation thermodynamics follows a strong enthalpy-entropy compensation relationship. Cyclophane 2 with 4 quaternary ammonium centers shows a much higher non-aggregated water-solubility than I with its two quaternary centers and forms stable steroid inclusion complexes in pure water. Complexes of anionic steroids with 2 are stabilized by both apolar interactions and ion pairing.