In nature, proteins have evolved sophisticated cavities tailored for capturing target guests selectively among competitors of similar size, shape, and charge. The fundamental principles guiding the molecular recognition, such as self-assembly and complementarity, have inspired the development of biomimetic receptors. In the current work, we report a self-assembled triple anion helicate (host 2) featuring a cavity resembling that of the choline-binding protein ChoX, as revealed by crystal and density functional theory (DFT)-optimized structures, which binds choline in a unique dual-site-binding mode. This similarity in structure leads to a similarly high selectivity of host 2 for choline over its derivatives, as demonstrated by the NMR and fluorescence competition experiments. Furthermore, host 2 is able to act as a fluorescence displacement sensor for discriminating choline, acetylcholine, L-carnitine, and glycine betaine effectively.The choline-binding protein ChoX exhibits a synergistic dual-site binding mode that allows it to discriminate choline over structural analogues. Here, the authors design a biomimetic triple anion helicate receptor whose selectivity for choline arises from a similar binding mechanism.

Chemical Sciences Division Oak Ridge National Laboratory Oak Ridge TN 37831 6119 USA

Department of Chemistry Ben Gurion University of the Negev 84105 Beer Sheva Israel

Department of Physical and Macromolecular Chemistry Faculty of Science Charles University Prague Albertov 6 12843 Czech Republic

Department of Physical Chemistry Regional Centre of Advanced Technologies and Materials Palacký University 77146 Olomouc Czech Republic

Institute of Organic Chemistry and Biochemistry 16010 Prague 6 Czech Republic

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education College of Chemistry and Materials Science Northwest University 710069 Xi'an China

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