New Molecular Motif for Recognizing Sialic Acid Using Emissive Lanthanide–Macrocyclic Polyazacarboxylate Complexes: Deprotonation of a Coordinated Water Molecule Controls Specific Binding

Abstract

A new molecular motif--lanthanide-macrocyclic polyazacarboxylate hexadentate complexes, Ln(3+)-ABNOTA--was found to specifically bind to sialic acid with strong emission enhancement and high affinity. The selectivity toward sialic acid over other monosaccharides was one of the highest among artificial receptors. Also, the novel binding mechanism was investigated in detail; binding selectivity is controlled by interactions between sialic acid and both the central metal and a hydroxyl group produced by deprotonation of a coordinated water molecule in the Ln(3+) complex.

Affinity Capillary Electrophoresis for Selective Control of Electrophoretic Mobility of Sialic Acid Using Lanthanide-Hexadentate Macrocyclic Polyazacarboxylate Complexes

“…The extent of the shift depended on the concentration of the Ln-NOTA complex. These facts strongly suggest that the Ln-NOTA complex interacts with Neu5Ac, as reported for Ln-ABNOTA, 37 to form a higher charge density species, [(Neu5Ac) --(Ln-NOTA-OH -)] 2-(see Fig. 1).…”

“…In our previous studies, 36,37 it was found that some lanthanidepolyaminocarboxylate complex motifs strongly and selectively bound with Neu5Ac with an affinity of ~10 3.6 L/mol, which is the highest affinity among artificial receptors reported so far. The Tb-ABNOTA complex (whose chemical structure is shown in Fig.…”

“…It was reported that species of the acid-dissociated complex ([Ln-NOTA-OH] -) were involved in one-to-one ternary complex formation, whereas non-dissociated species, [Ln-NOTA-H2O], showed no reactivity with Neu5Ac in bulk solution. 37 Thus, there is no need to take the complexation equilibrium between [Ln-NOTA-H2O] and Neu5Ac into consideration. Thus, the reaction at a certain pH can be represented by the following equations:…”

“…The pKa,Ln-ABNOTA value obtained for Tb 3+ , 9.65 ± 0.07, is similar to those determined by other methods, 9.44 ± 0.07 (CE) and 9.4 ± 0.2 (fluorometry). 37 While it was expected that the side-chain, such as an aminobenzyl group, would show no effect on the pKa of the acid-dissociation reaction of the coordinated water molecule in the Ln-NOTA structure, the pKa values for Ln-FTC-ABNOTA complexes (where FTC represents fluorescein-thiocarbamyl) were determined to be 10.1 ± 0.1, 9.8 ± 0.2, 8.7 ± 0.2 for Nd, Gd and Lu, 39 respectively, which are comparable to those of Ln-ABNOTA complexes in this study (for example, 8.92 for the Lu-ABNOTA complex). As such, the estimation that the pKa values of Ln-NOTA complexes are very similar to those of Ln-ABNOTA complexes is reasonable, providing estimated KNeu5Ac-Ln-NOTA values, as summarized in Table 1.…”

“…1A) especially provided high affinity and significant Lnbased emission enhancement in a slightly alkaline aqueous solution. 37 The unique mechanism of the recognition of Neu5Ac is as follows: there are two or three residual coordination sites in the Ln-ABNOTA complex, since the coordination numbers for the Ln ion and the ABNOTA ligand are 8 -9 and 6, respectively. Hence, two or three water molecules usually coordinate to form a complex of [Ln Thus, this same motif is expected to be desirable for ACE for sialic acid in terms of changing the charge on the Neu5Ac…”