Sandwich-Like Complexation of Carbohydrates by Hydrogen Bonding and CH-π Interactions

Abstract

Introduction: The design of carbohydrate-binding agents (artificial carbohydrate receptors) that enable selective and effective biomimetic recognition via noncovalent interactions is aimed either at a better understanding of natural recognition phenomena or at various potential applications in medicine and other fields. Although very interesting artificial receptors have been developed, the exact prediction of the receptor selectivity remains a challenge. Results and Methods: A molecular architecture based on a 1,3,5-substituted 2,4,6-triethylbenzene backbone bearing two aminopyridine- or aminopyrimidine-based recognition units and a purine moiety, which acts as both a hydrogen bonding site and a bridging component for the incorporation of additional substituents, has proved to be very useful for the development of effective carbohydrate-binding agents. This type of compounds has the ability to bind suitable carbohydrates through combined noncovalent interactions, where CH···π interactions can be formed on both faces of the carbohydrate substrate. The successful syntheses of the target compounds can be realized by the use of microwave irradiation and sealed tubes. The performed binding studies included 1H NMR spectroscopic titrations and measurements by isothermal titration calorimetry. Conclusion: The new compounds were developed as artificial receptors especially for carbohydrates with an all-equatorial substitution pattern and have the ability to predictably form strong 1:1 complexes with a suitable substrate. The use of the purine moiety in the construction of carbohydrate receptors with a 1,3,5-substituted 2,4,6-triethylbenzene backbone has proved to be a very promising approach. The possibilities for structural variation of this molecular architecture are manifold. As a result, a wide range of compounds can be synthesized to perform extensive studies on the relationships between structure and binding efficiency. Graphical Abstract Short Text: New compounds were developed as artificial receptors especially for carbohydrates with an all-equatorial substitution pattern and have the ability to predictably form 1:1 complexes with a suitable substrate. Key Topics: Artificial carbohydrate receptors; Combination of hydrogen bonding and CH۔۔۔π interactions; Molecular recognition