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 À 1 ), used as a template, much strongly than l-tartaric acid (326 M À 1 ). In contrast, its modified receptor P-7 exhibited significantly reduced affinities for d-tartaric acid (3600 M À 1 ) and l-tartaric acid (125 M À 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 dsorbitol (52000 M À 1 ) over analogous guests, but P-8 showed no binding selectivity: d-sorbitol (1890 M À 1 ), l-sorbitol (3330 M À 1 ), d-arabitol (959 M À 1 ), l-arabitol (4970 M À 1 ) and xylitol (4960 M À 1 ) in 5% (v/v) DMSO/CH 2 Cl 2 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.

Carbohydrate recognition using metal–ligand assemblies

“…Various research groups, including Mazik, 17 Braunschweig, 18 and others, 19 have prepared numerous flexible ACRs using a variety of heterocycles linked by polar groups such as amide, urea, thiourea, and guanidine that are suitable for binding various mono-, di-, and oligosaccharides. Huc, 20 Inouye, 21 and Jeong 22 employed foldamer-based aromatic oligoamide receptors to wrap sugars with high binding affinities in organic solvents. Davis and co-workers have constructed “temple receptors”, covalent macrocycles and covalent cages that exhibit a wide range of binding affinities for various carbohydrates, from moderate to good selectivity, in both organic and aqueous media.…”