1,8-Naphthridine Based Receptors for Selective Monosaccharide Binding in Aqueous Media

In this dissertation the synthesis, characterization, and binding properties of
carbohydrate receptors 34-38 was described. Macrocyclic receptor 34 and macrobicyclic
receptor 35 bind monosaccharides in aqueous media through combination of
hydrophobic, electrostatic and hydrogen bonding interactions. The dissociation constants
(Kd) for the complexes between 1 ,8-naphthyridine receptors 34, and 35 with a variety of
neutral and negatively charged monosaccharides in aqueous media were determined by
fluorimetric and UV /vis titration. The observed values are in the range from ~0.3 to >10
mM, within the Kd range reported for lectin/monosaccharide complexes. However,
among monosaccharide substrates tested receptor 34 showed the strongest affinity for
sialic acid (Kd = ~0 . 3 mM), a monosaccharide that plays many important roles in a wide
variety of physiological and pathological processes. Macrocyclic receptor 34 recognizes not only sialic acid in solution, but also binds selectively in vitro to human
cancer cell surface carbohydrate antigens containing terminal sialic acid moieties. In
addition, besides their binding selectivity, receptors 34 and 35 display also the ability to
discriminate between closely related monosaccharide substrates by opposite variation of
the fluorescence emission intensity. Structure-binding relationship study of receptor 34
revealed that H-bonding donor/acceptor pattern and presence of positive charge on
receptor's side arms are crucial for selective monosaccharide binding in aqueous media.