The synthesis, characterization, and steroid binding properties of two
novel cyclophane receptors shaped by two naphthylphenylmethane spacer
s are reported. Cyclophane 1 forms inclusion complexes with bile acids
, corticoids, and androgenic steroids in D2O/CD3OD 1:1. Specific funct
ional 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 com
plex of deoxycholic acid. Steroid complexation by I is enthalpically d
riven, and complexation thermodynamics follows a strong enthalpy-entro
py compensation relationship. Cyclophane 2 with 4 quaternary ammonium
centers shows a much higher non-aggregated water-solubility than I wit
h its two quaternary centers and forms stable steroid inclusion comple
xes in pure water. Complexes of anionic steroids with 2 are stabilized
by both apolar interactions and ion pairing.