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

Abstract

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/CH₂ Cl₂ 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.

Keywords: Aromatic foldamers; Binding affinity; Chiral guests; Helical receptors; Post-modification.