Molecular Recognition of Sialic Acid by Lanthanide(III) Complexes through Cooperative Two-Site Binding

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• 作者：Martn Regueiro-Figueroa ; Kristina Djanashvili ; David Esteban-Gmez ; Thomas Chauvin ; va Tth ; Andrs de Blas ; Teresa Rodrguez-Blas ; Carlos Platas-Iglesias
• 刊名：Inorganic Chemistry
• 出版年：2010
• 出版时间：May 3, 2010
• 年：2010
• 卷：49
• 期：9
• 页码：4212-4223
• 全文大小：1055K
• 年卷期：v.49,no.9(May 3, 2010)
• ISSN：1520-510X

文摘

Herein we report two new ligands, 1,4,7-tris(carboxymethyl)-10-[2-(dihydroxyboranyl)benzyl]-1,4,7,10-tetraazacyclododecane (L¹) and 1,4,7-tris(carboxymethyl)-10-[3-(dihydroxyboranyl)benzyl]-1,4,7,10-tetraazacyclododecane (L²), 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(L¹)] and 8.9 in [Gd(L²)], with the value of the L² analogue being very similar to that of PBA (8.8). These results are explained by the coordination of the PBA function of L¹ to the Gd^III ion, which results in a dramatic lowering of its pK_a. As a consequence, [Gd(L¹)] does not bind to saccharides at physiological pH. The nuclear magnetic relaxation dispersion profiles recorded for [Gd(L¹)] and [Gd(L²)] confirm that the phenylboronate function is coordinated to the metal ion in the L¹ derivative, which results in a q = 0 complex. The interaction of the [Gd(L²)] complex with 5-acetylneuraminic acid (Neu5Ac) and 2-α-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 α-d-galactoside, and methyl α-d-mannoside. The binding constants obtained indicate an important selectivity of [Gd(L²)] for Neu5Ac (K_eq = 151) over d-(+)-glucose (K_eq = 12.3), d-mannose (K_eq = 21.9), and d-galactose (K_eq = 24.5). Furthermore, a very weak binding affinity was observed in the case of methyl α-d-galactoside and methyl α-d-mannoside. An 8-fold increase of the binding constant of [Gd(L²)] with Neu5Ac is observed when compared to that of PBA determined under the same conditions (K_eq = 19). ¹³C NMR spectroscopy and density functional theory calculations performed at the B3LYP/6-31G(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 Gd^III ion. The emission lifetime of the ⁵D₄ level of Tb^III in [Tb(L²)] increases upon Neu5Ac binding, in line with the displacement of inner-sphere water molecules due to coordination of Neu5Ac to the metal ion.