A Synthetic Lectin for Glucuronate.

The selective recognition of hydrophilic carbohydrates in water remains a longstanding challenge in supramolecular chemistry due to solvent competition and the lack of a strong driving force comparable to the hydrophobic effect. Herein, we report the design, synthesis, and characterization of a water-soluble tetralactam macrocycle, MPNT·2Cl, as a highly effective synthetic lectin for glucuronate. MPNT·2Cl features two dimethylnaphthalene panels, pyridinium spacers, and morpholine side chains, forming a rigid, preorganized cavity with convergent hydrogen bond donors, polarized C-H donors, and complementary electrostatic interactions. The receptor achieves a binding affinity of 103,000 M for glucuronate in water, over 19-fold higher than previous synthetic systems, along with excellent selectivity over structurally similar carbohydrates. Single-crystal X-ray analysis, DFT calculation, and IGMH analysis reveal a dense network of [N-H···O], [C-H···O], and [C-H···π] interactions, highlighting the role of stereoelectronic complementarity in complex formation. Moreover, MPNT·2Cl acts as a chiroptical sensor, producing binding-induced circular dichroism signals that enable sensitive detection of glucuronic acid at physiologically relevant concentrations. This work presents a generalizable strategy for designing synthetic lectins that recognize carbohydrates in aqueous solutions and opens up new possibilities for developing molecular sensors and diagnostic tools for biologically important anionic sugars.