1,8-Naphthyridine Based Artificial Receptors for Selective Monosaccharide Binding in Water

Abstract

1,8-Naphthyridine based bi-bracchial macrocyclic 2 and cage-type macrobicyclic receptor 3 bind monosaccharides in water under physiologically relevant conditions through a combination of hydrophobic, electrostatic and hydrogen bonding interactions. The dissociation constants (Kd) for the complexes between 1,8-naphthyridine receptors 1-3 with a variety of neutral and negatively charged monosaccharides in water were determined by fluorimetric and UV/vis titration. The observed values are in the range from ˜ 0.3 to ≥10 mM, and are similar to the Kd reported for lectin/monosaccharide complexes. Among the monosaccharide substrates tested, receptor 2 showed the strongest binding affinity for sialic acid (Kd = ˜ 0.3 mM), a monosaccharide that plays many important roles in a wide variety of physiological and pathological processes. Interestingly, receptors 2 and 3 display the ability to discriminate between closely related monosaccharide substrates by opposite variation of the fluorescence emission intensity. Keywords: 1,8-Naphthyridine receptors, sialic acid, lectin mimetics, physiologically relevant conditions, selective binding, cell-cell recognition, inflammation, cell differentiation, tumor cell colonization, metastasis, anticancer drugs, supramolecular chemistry, organic solvents, fluorescence, condensation, buffer