Harnessing non-covalent interactions synthesis & catalysis

Optimising artificial enzymes by altering the nature of the active metal complex Rosalind Booth, L Gečiauskas, A. Miller, G. Grogan, K.S. Wilson, A-K Duhme-Klair University of York, UK Artificial metalloenzymes can enhance the catalytic capabilities of transition metal catalysts by contributing a complex network of complementary interactions by introducing a protein scaffold. 1,2 Several approaches to designing artificial metalloproteins are being investigated, with catalytically active metal sites being incorporated into proteins by a variety of methods. Our design utilizes a small protein involved in the iron-uptake pathway in some microorganisms. 3 By attaching a catalytically-active metal complex to an iron chelator, we can position the catalyst inside our protein scaffold. An iridium transfer hydrogenation catalyst was selected to target imine reduction, and in combination with our artificial metalloenzyme design initially achieved moderate catalytic rate and selectivity. Through tuning of the steric and electronic properties of the iridium-coordinating ligands, both the selectivity and catalytic rate of the reaction were improved. In addition, the uses of similar thermophilic proteins have further enhanced artificial metalloenzyme performance.

References 1. J. Collot, J. Gradinaru, N. Humbert, M. Skander, A. Zocchi and T. R. Ward, J. Am. Chem. Soc., 2003, 125 , 9030-9031. 2. F. Schwizer, Y. Okamoto, T. Heinisch, Y. Gu, M. M. Pellizzoni, V. Lebrun, R. Reuter, V. Köhler, J. C. Lewis and T. R. Ward, Chem. Rev. , 2018, 118 , 142-231. 3. D. J. Raines, J. E. Clarke, E. V. Blagova, E. J. Dodson, K. S. Wilson and A-K. Duhme-Klair, Nature Catalysis , 2018, 1 , 680- 688.

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