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A supramolecular approach to combining enzymatic and transition metal catalysis

Abstract

The ability of supramolecular host–guest complexes to catalyse organic reactions collaboratively with an enzyme is an important goal in the research and discovery of synthetic enzyme mimics. Herein we present a variety of catalytic tandem reactions that employ esterases, lipases or alcohol dehydrogenases and gold(I) or ruthenium(II) complexes encapsulated in a Ga4L6 tetrahedral supramolecular cluster. The host–guest complexes are tolerated well by the enzymes and, in the case of the gold(I) host–guest complex, show improved reactivity relative to the free cationic guest. We propose that supramolecular encapsulation of organometallic complexes prevents their diffusion into the bulk solution, where they can bind amino-acid residues on the proteins and potentially compromise their activity. Our observations underline the advantages of the supramolecular approach and suggest that encapsulation of reactive complexes may provide a general strategy for carrying out classic organic reactions in the presence of biocatalysts.

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Figure 1: Host–guest complexes of Ga4L6 with Au(I) complexes can facilitate the hydroalkoxylation of an allene in water.
Figure 2: Reaction progress of the hydrolysis of 12 with hog liver esterase in the presence of Me3PAu+ 1, Me3PAuCl (free Au) or no additional gold complex.
Figure 3

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Acknowledgements

This work was supported by the Director, Office of Science, Office of Basic Energy Sciences, and the Division of Chemical Sciences, Geosciences and Biosciences of the US Department of Energy at Lawrence Berkeley National Laboratory. Z.J.W. thanks the Hertz Foundation for a graduate fellowship and C. Brown for help in syntheses of the starting materials.

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Contributions

Z.J.W. conceived and designed the initial experiments and performed the kinetic studies. K.N.C. performed the kinetic resolution experiments and measured the diastereoselectivity and enantioselectivity of the transformations. Z.J.W. prepared the manuscript with help from K.N.C. All the authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Robert G. Bergman, Kenneth N. Raymond or F. Dean Toste.

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The authors declare no competing financial interests.

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Wang, Z., Clary, K., Bergman, R. et al. A supramolecular approach to combining enzymatic and transition metal catalysis. Nature Chem 5, 100–103 (2013). https://doi.org/10.1038/nchem.1531

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