Subtle Modification of Imine-linked Helical Receptors to Significantly Alter their Binding Affinities and Selectivities for Chiral Guests

Aromatic helical receptors P- 1 and P- 2 were slightly modified by aerobic oxidation to afford new receptors P- 7 and P- 8 with right-handed helical cavities. This subtle modification induced significant changes in the binding properties for chiral guests. Specifically, P- 1 was reported to bind d -tartaric acid (K_a=35500 M⁻¹), used as a template, much strongly than l -tartaric acid (326 M⁻¹). In contrast, its modified receptor P- 7 exhibited significantly reduced affinities for d -tartaric acid (3600 M⁻¹) and l -tartaric acid (125 M⁻¹). More dramatic changes in the affinities and selectivities were observed for P- 2 and P- 8 upon binding of polyol guests. P- 2 was determined to selectively bind d -sorbitol (52000 M⁻¹) over analogous guests, but P- 8 showed no binding selectivity: d -sorbitol (1890 M⁻¹), l -sorbitol (3330 M⁻¹), d -arabitol (959 M⁻¹), l -arabitol (4970 M⁻¹) and xylitol (4960 M⁻¹) in 5% (v/v) DMSO/CH₂Cl₂ at 25±1 °C. These results clearly demonstrate that even subtle post-modifications of synthetic receptors may significantly alter their binding affinities and selectivities, in particular for guests of long and flexible chains.