Phase Transfer of Monosaccharides Through Noncovalent Interactions

Authors

Anthony P. Davis Department of Chemistry, University of Bristol

Publication Date

4/20/04

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Abstract

Sugars constitute one of the major classes of biological building blocks. On one hand, they are important for physical construction (e.g., as cellulose) and energy storage (e.g., as starch). On another more subtle level, they are used by nature to label cells and biomolecules and thus to mediate a variety of biological events. Thus saccharide motifs are central to cell–cell recognition, infection of cells by pathogens, and many aspects of the immune response.

Carbohydrates are hydrophilic molecules, which are usually freely soluble in water and show little inclination to enter organic media. Nonetheless, there are good reasons why one might wish to promote phase transfer of these species. First, there is a potential large-scale technological application in the production of “high-fructose syrup.” Hydrolysis of starch and enzymatic treatment can be used to produce a mixture of fructose and glucose, which is ca. 42% of the former. Higher levels are desirable as fructose is exceptionally sweet-tasting, and there is much interest in transport processes that might be used in enrichment procedures. Second, there are biomedical applications for carbohydrate phase transfer. The most immediate might be in the management of diabetes, where an effective, reversible extraction system could be used as the basis for a glucose sensor. In addition, there is fundamental interest in saccharide transport across biological membranes and the possibility of delivering carbohydrate-like drugs using phase-transfer agents. Third, the study of carbohydrate recognition has become a major area of supramolecular chemistry, and carbohydrate phase transfer has proved useful in this context. The key challenge is to bind carbohydrates in direct competition with liquid water (their natural environment). However, it is difficult to design and handle receptors that are fully soluble in water. Extraction experiments, involving aqueous and organic phases, provide a straightforward solution to the problem. The receptor, dissolved in the organic solvent, is equilibrated with an aqueous solution of the substrate. The amount of substrate transferred to the organic phase can be measured and used as a qualitative indication of receptor efficiency. Quantification is possible in principle, although to date this has not been realized for carbohydrate substrates.

Broadly speaking, two approaches have been taken toward carbohydrate recognition in general, and toward carbohydrate phase transfer in particular. One is based on the reaction of boronic acids with diols to give cyclic boronate esters. This strategy can be highly effective but, being based on covalent BO bond formation, lacks biological relevance. The alternative relies on noncovalent interactions, and thus may be seen as “biomimetic.” This entry discusses systems belonging to the second category only, focusing on the transfer/transport of simple monosaccharide substrates into/across nonpolar phases. The account is divided into three sections covering: 1) preorganized receptor molecules; 2) less organized, micellar systems; and 3) self-assembling channels.