Abstract
Reversible covalent bonding is often used for the creation of novel supramolecular structures, multi-component assemblies and sensing ensembles. Despite the remarkable success of dynamic covalent systems, the reversible binding of a mono-alcohol with high strength is challenging. Here, we show that a strategy of carbonyl activation and hemiaminal ether stabilization can be embodied in a four-component reversible assembly that creates a tetradentate ligand and incorporates secondary alcohols with exceptionally high affinity. Evidence is presented that the intermediate leading to binding and exchange of alcohols is an iminium ion. To demonstrate the use of this assembly process we also explored chirality sensing and enantiomeric excess determinations. An induced twist in the ligand by a chiral mono-ol results in large Cotton effects in the circular dichroism spectra indicative of the handedness of the alcohol. The strategy revealed in this study should prove broadly applicable for the incorporation of alcohols into supramolecular architecture construction.
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Acknowledgements
The authors thank B. Shoulders and S. Sorey for NMR assistance, K. Keller for mass spectrometric assistance and E.J. Cho of the Texas Institute for Drug and Diagnostic Development. The authors are grateful for the financial support provided by the National Institutes of Health (GM 077437) and the Welch Foundation (F-1151).
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L.Y. and E.V.A. developed the strategy and the mechanistic concepts. L.Y. performed the experiments. J.S.B. participated in the reaction optimization. E.V.A. directed the research. L.Y. and E.V.A. wrote the manuscript.
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You, L., Berman, J. & Anslyn, E. Dynamic multi-component covalent assembly for the reversible binding of secondary alcohols and chirality sensing. Nature Chem 3, 943–948 (2011). https://doi.org/10.1038/nchem.1198
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DOI: https://doi.org/10.1038/nchem.1198
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