Abstract
In biological systems, enzymes and transport proteins can bind anions in aqueous media solely by forming hydrogen bonds with charge-neutral motifs. Reproducing this functionality in synthetic systems presents challenges and incurs high costs, particularly when targeting strongly hydrated anions such as sulfate. Here we report a [2.2.2]urea cryptand (cage), synthesized in one pot, that selectively binds sulfate in a mixture of dimethyl sulfoxide and water and in water with affinities in the micromolar to millimolar range. The neutral cage bearing six urea groups donates 12 strong hydrogen bonds to encapsulate a sulfate anion, showing favourable enthalpy even in pure water. Sulfate binding can be further enhanced by using micelles to provide a low-polarity microenvironment. The cage finds utility in analysing divalent anions in water and beverage samples or in removing sulfate. The work demonstrates the achievability of robust and selective anion binding in water with minimal synthetic efforts, by using neutral NH hydrogen bonds akin to those found in biology.
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Data availability
Data supporting the findings of this study are available from the manuscript and its Supplementary Information. The raw data have been deposited in Figshare at https://doi.org/10.6084/m9.figshare.21776117. Crystallographic data for the structures reported have been deposited at the Cambridge Crystallographic Data Centre under deposition numbers CCDC 2220230 (1), 2223225 (1–TBA2SO4) and 2220513 (4–TBA2SO4). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Source data are provided with this paper.
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Acknowledgements
We acknowledge the support from the Australian Research Council (DE220101000, X.W. and LE170100144, J.K.C.), the National Natural Science Foundation of China (21820102006 and 92356308, X.W.), the University of Queensland and Xiamen University. Part of this research was undertaken at the MX1 beamline at the Australian Synchrotron, part of ANSTO. We thank the Australian Synchrotron for travel support, and their staff for assistance. The computational work was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government, and resources provided by the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. E.D. thanks M. Stroet (the University of Queensland) for assistance with the Automated Topology Builder. We thank P. A. Gale (University of Technology Sydney) and N. Busschaert (Tulane University) for providing compound 2 for NMR studies. We thank X.-S. Yan (Xiamen University) for providing reagents and laboratory space during manuscript revision. We thank M. Carpinelli de Jesus (the University of Queensland) for help in ion chromatography experiments. We thank J.-J. Chen (the Analysis and Measurement Center, School of Pharmaceutical Sciences, Xiamen University) for performing data analysis on the isothermal calorimetry.
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X.W. conceived and directed the project. L.J. and X.W. performed the experiments. E.D. designed and performed the computational studies. J.K.C. supervised the crystallographic studies and advised on the project. All authors discussed the results and commented on the manuscript.
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Supplementary Information
Supplementary Figs. 1–54, Supplementary Tables 1–11, Supplementary Methods and Supplementary Discussion.
Supplementary Data 1
Crystallographic information file for 1; CCDC reference 2220230.
Supplementary Data 2
Crystallographic information file for 1–TBA2SO4; CCDC reference 2223225.
Supplementary Data 3
Crystallographic information file for 4–TBA2SO4; CCDC reference 2220513.
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Numerical data for Fig. 4.
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Jing, L., Deplazes, E., Clegg, J.K. et al. A charge-neutral organic cage selectively binds strongly hydrated sulfate anions in water. Nat. Chem. 16, 335–342 (2024). https://doi.org/10.1038/s41557-024-01457-5
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DOI: https://doi.org/10.1038/s41557-024-01457-5
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