Herein we report two new ligands, 1,4,7-tris(carboxymethyl)-10-[2-(dihydroxyboranyl)benzyl]-1,4,7,10-tetra azacyclododecane (L-1) and 1,4,7-tris(carboxymethyl)-10-[3-(dihydroxyboranypbenzyl]-1,4,7,10-tetraa zacyclododecane (L-2), which contain a phenylboronic acid (PBA) function and a 1,4,7,10-tetraazacyclododecane-1,4,7-triacetate cage for complexation of lanthanide ions in an aqueous solution The pK(a) of the PBA function amounts to 4.6 in [Gd(L-1)] and 8.9 in [Gd(L-2)], with the value of the L-2 analogue being very similar to that of PBA (8 8) These results are explained by the coordination of the PBA function of L-1 to the Ge-III ion, which results in a dramatic lowering of its pKa. As a consequence, [Gd(L-1)] does not bind to saccharides at physiological pH. The nuclear magnetic relaxation dispersion profiles recorded for [Gd(L-1)] and [Gd(L-2)] confirm that the phenylboronate function is coordinated to the metal ion in the L-1 derivative, which results in a q=0 complex The interaction of the [Gd(L-2)] complex with 5-acetylneuraminic acid (Neu5Ac) and 2-alpha-O-methyl-5-acetylneuraminic acid (MeNeu5Ac) has been investigated by means of spectrophotometric titrations in an aqueous solution (pH 7 4, 0 1 M 3-(N-morpholino)propanesulfonic acid buffer). Furthermore, we have also investigated the binding of these receptors with competing monosaccharides such as D-(+)-glucose, D-fructose, D-mannose, D-galactose, methyl alpha-D-galactoside, and methyl alpha-D-mannoside. The binding constants obtained indicate an important selectivity of [Gd(L-2)] for Neu5Ac (K-eg = 151) over D-(+)-glucose (K-eg = 12.3), D-mannose (K-eg=21 9), and D-galactose (K-eq=24 5). Furthermore, a very weak binding affinity was observed in the case of methyl alpha-D-galactoside and methyl alpha-D-mannoside. An 8-fold increase of the binding constant of [Gd(L-2)] with Neu5Ac is observed when compared to that of PBA determined under the same conditions (Keg = 19) C-13 NMR spectroscopy and density functional theory calculations performed at the B3LYP/6-31 G(d) level show that this is due to a cooperative two-site binding of Neu5Ac through (1) ester formation by interaction on the PBA function of the receptor and (2) coordination of the carboxylate group of Neu5Ac to the Ge-III ion The emission lifetime of the D-5(4) level of Tb-III in [Tb(L-2)] increases upon Neu5Ac binding, in line with the displacement of inner-sphere water molecules due to coordination of Neu5Ac to the metal ion.