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A Synthetic Lectin for Glucuronate

2025/08/01 by Canjia Zhai, Chengkai Xu, Yunpeng Cui +3 · 1 voice
Chemistry · Materials Science · #Carbohydrate Chemistry and Synthesis #Molecular Sensors and Ion Detection #Supramolecular Self-Assembly in Materials

paper · doi:10.1021/acscentsci.5c00951

openalex publication_date 2025/08/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/15

Abstract

High Resolution Image Download MS PowerPoint Slide 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 2+ ·2Cl –, as a highly effective synthetic lectin for glucuronate. MPNT 2+ ·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 –1 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 2+ ·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.

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