Probing the Importance of Host Symmetry on Carbohydrate Recognition

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, C₃ - and C₁ -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 C₃ -symmetrical analogue. According to the host cavity modelling, the C₁ symmetry receptor exhibits a wider opening than its C₃ -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 C₁ symmetry cage with respect to its C₃ counterpart in the recognition of sugars.