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, MPNT2+·2Cl–, as a highly effective synthetic
lectin for glucuronate. MPNT2+·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, MPNT2+·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.

水中亲水糖类的选择性识别始终是超分子化学领域的长期难题，究其根源在于溶剂竞争效应，且缺乏可与疏水作用相提并论的强结合驱动力。在此，我们报道了一种水溶性四内酰胺大环化合物MPNT²⁺·2Cl⁻的设计、合成与表征，其作为靶向葡萄糖醛酸酯的高效合成凝集素。MPNT²⁺·2Cl⁻包含两个二甲基萘平面单元、吡啶𬭩间隔基与吗啉侧链，可形成刚性且预组织的空腔，该空腔带有会聚型氢键给体、极化C-H给体以及互补静电相互作用位点。该受体在水中对葡萄糖醛酸酯的结合亲和力可达103000 M⁻¹，较此前的合成体系高出19倍以上，同时对结构相似的糖类展现出优异的选择性。单晶X射线衍射分析、密度泛函理论（DFT）计算以及IGMH分析揭示了由[N-H···O]、[C-H···O]与[C-H···π]相互作用构成的致密网络，凸显了立体电子互补性在复合物形成过程中的关键作用。此外，MPNT²⁺·2Cl⁻可作为手性光学传感器，产生结合诱导型圆二色性信号，能够在生理相关浓度下实现对葡萄糖醛酸的灵敏检测。本工作提出了一种可推广的设计策略，用于开发在水溶液中识别糖类的合成凝集素，同时为面向生物重要阴离子糖类的分子传感器与诊断工具的开发开辟了新的可能性。