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Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage

Nature Chemistry volume 8, pages 231–236 (2016)Cite this article

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Abstract

The hollow cavities of coordination cages can provide an environment for enzyme-like catalytic reactions of small-molecule guests. Here, we report a new example (catalysis of the Kemp elimination reaction of benzisoxazole with hydroxide to form 2-cyanophenolate) in the cavity of a water-soluble M8L12 coordination cage, with two features of particular interest. First, the rate enhancement is among the largest observed to date: at pD 8.5, the value of kcat/kuncat is 2 × 105, due to the accumulation of a high concentration of partially desolvated hydroxide ions around the bound guest arising from ion-pairing with the 16+ cage. Second, the catalysis is based on two orthogonal interactions: (1) hydrophobic binding of benzisoxazole in the cavity and (2) polar binding of hydroxide ions to sites on the cage surface, both of which were established by competition experiments.

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Figure 1: Structure of the host cage [Co8L12](BF4)16.
Figure 2: The Kemp elimination reaction.
Figure 3: pD dependence of reaction rate constants.
Figure 4: Crystal structure of the cage–benzisoxazole complex.
Figure 5: Cartoon of the catalytic reaction cycle.
Figure 6: Demonstration of catalytic turnover with the cage catalyst.

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Acknowledgements

The authors acknowledge financial support from the Engineering and Physical Sciences Research Council (EPSRC).

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Authors and Affiliations

  1. Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK

    William Cullen, Nicholas H. Williams & Michael D. Ward

  2. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK

    M. Cristina Misuraca & Christopher A. Hunter

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  1. William Cullen
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  2. M. Cristina Misuraca
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  3. Christopher A. Hunter
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Contributions

W.C. performed the synthesis, crystallography and most of the experimental measurements. M.C.M. helped to design the experiment and performed some of the initial experimental measurements. C.A.H., N.H.W. and M.D.W. jointly conceived and designed the experiments, analysed the results and wrote the manuscript.

Corresponding authors

Correspondence to Christopher A. Hunter, Nicholas H. Williams or Michael D. Ward.

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The authors declare no competing financial interests.

Supplementary information

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Supplementary information (PDF 2001 kb)

Supplementary information

Crystallographic data for [Co8(Lw)12](BF4)16●(C7H5NO) (CIF 157 kb)

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Structure factors for [Co8(Lw)12](BF4)16●(C7H5NO) (FCF 1246 kb)

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Cullen, W., Misuraca, M., Hunter, C. et al. Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage. Nature Chem 8, 231–236 (2016). https://doi.org/10.1038/nchem.2452

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