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Dynamic multi-component covalent assembly for the reversible binding of secondary alcohols and chirality sensing

Nature Chemistry volume 3, pages 943948 (2011) | Download Citation

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.

  • Compound C6H5NO

    Pyridine-2-carboxaldehyde

  • Compound C12H13N3

    Di-(2-picolyl)amine

  • Compound C20H18F6N4O7S2Zn

    [(Bis(pyridin-2-ylmethyl)amino)(pyridin-2-yl)methanol]zinc(II) bis(trifluoromethanesulfonate)

  • Compound C18H17N4+

    1-(Pyridin-2-yl)-N-(pyridin-2-ylmethyl)-N-(pyridin-2-ylmethylene)methanaminium

  • Compound C3H8O

    Isopropyl alcohol

  • Compound C23H24F6N4O7S2Zn

    [1-Isopropoxy-1-(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine]zinc(II) bis(trifluoromethanesulfonate)

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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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Affiliations

  1. Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, USA

    • Lei You
    • , Jeffrey S. Berman
    •  & Eric V. Anslyn

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Eric V. Anslyn.

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https://doi.org/10.1038/nchem.1198

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