MOLECULAR RECOGNITION OF CARBOHYDRATES USING A SYNTHETIC RECEPTOR - A MODEL SYSTEM TO UNDERSTAND THE STEREOSELECTIVITY OF A CARBOHYDRATE-CARBOHYDRATE INTERACTION IN WATER

We have determined by H-1 NMR the association constants between a synthetic receptor, glycophane 1, and a series of 4-nitrophenyl and 2,4-dinitrophenyl glycosides (D-gluco, D-galacto, D-manno, D-xylo, L-arabino, and L-fuco) with axial and equatorial configuration at the anomeric center. The results indicate both a stabilization of the complexes due to the carbohydrate moieties and a stereoselectivity in the interaction, The equatorial glycosides are complexed with similar free energies of binding (similar to 2.7 Kcal . mol(-1)), while in the axial glycosides the free energy of binding changes with the stereochemistry of the sugar (from 2.6 to 3.3 Kcal . mol(-1)), In contrast, the complexes formed between alpha-cyclodextrin and the 4-nitrophenyl glycosides did not show either additional stabilization nor selectivity due to the carbohydrate moieties. Differential changes in the free energy of binding in the glycophane 1-4-nitrophenyl glycosides complexes result from changes in the chemical nature of the substituents of the guest. The Delta G also changes with the orientation of the hydroxyl groups that are in contact with the receptor but do not necessarily participate in hydrogen bonding interactions. Molecular mechanics and dynamics calculations gave different geometries for the axial and equatorial glycosides which agree with the geometries expected based on the H-1 NMR data. The results show that in our models lipophilic forces between carbohydrate surfaces mainly determine the stability of the association. Parallels are drawn between the forces involved in our models and those proposed for the biological associations of carbohydrates.