Probing the Importance of Host Symmetry on Carbohydrate Recognition

A simple switch from formic acid to HFIP allows the formation of the C ₃ symmetrical hemicryptophane cage analogue of the previously reported C ₁ symmetrical one. The cage with low symmetry exhibits higher binding constants towards carbohydrates than the C ₃ analogue. The receptors showed remarkable high substrate selectivity and stereoselectivity towards α-glucoside and β-galactoside.

Abstract

The design of molecular cages with low symmetry could allow for more specific tuning of their properties and better mimic the unsymmetrical and complex environment of protein pockets. However, the added value of lowering symmetry of molecular receptors has been rarely demonstrated. Herein, C ₃- and C ₁-symmetrical cages, presenting the same recognition sites, have been synthesized and investigated as hosts for carbohydrate recognition. Structurally related derivatives of glucose, galactose and mannose were found to have greater affinity to the receptor with the lowest symmetry than to their C ₃-symmetrical analogue. According to the host cavity modelling, the C ₁ symmetry receptor exhibits a wider opening than its C ₃-symmetrical counterpart, providing easier access and thus promoting guest proximity to binding sites. Moreover, our results show the high stereo- and substrate selectivity of the C ₁ symmetry cage with respect to its C ₃ counterpart in the recognition of sugars.

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