GLYCOPHANES, CYCLODEXTRIN CYCLOPHANE HYBRID RECEPTORS FOR APOLAR BINDING IN AQUEOUS-SOLUTIONS - A STEREOSELECTIVE CARBOHYDRATE CARBOHYDRATE INTERACTION IN WATER

The synthesis and complexing properties of a new type of neutral chiral receptors, glycophanes 4-6 and 9-14, are reported. They may be considered as cyclodextrin-cyclophane hybrids because carbohydrate molecules, lipophilic cavities, and aromatic interactions are involved. They are built from alpha,alpha'-trehalose and 2,7-dihydroxynaphthalene or 4,4'-isopropylidenediphenol. The water soluble glycophane 12 displays a general affinity for electron-deficient aromatic guests (nitro derivatives of phenol and benzenesulfonic and benzenecarboxylic acids), the association constants increasing with the increased number of electron-withdrawing groups (NO2). Depending on the solvent, different factors seem to contribute to the stability of the complexes. In CD3OD:D2O (1:1), electron donor-acceptor interactions are the main driving forces, whereas in water, additional hydrophobic effects increase the stability of the complexes. Glycophane 12 shows chiral discrimination toward racemic mixtures of 2,4-dinitrophenyl amino acid derivatives in solid-liquid extraction experiments, with enantioselectivities ranging from 5 to 40% as deduced by integration of the aromatic proton NMR signals of both enantiomers. Cyclodextrins (CDs) under the same conditions did not show any discrimination toward these derivatives. A stereospecific carbohydrate-carbohydrate interaction in water has been shown between glycophane 12 and the 4-nitrophenyl alpha- and beta-D-gluco-, alpha- and beta-D-galacto- and alpha- and beta-D-mannopyranosyl derivatives, and the contribution of this interaction to complex stability has been evaluated. The complexes of CDs and 4-nitrophenyl glycosides did not show any additional stabilization due to carbohydrate moieties.