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Manel Boukhallat

Heterogeneous cascade oxidations catalyzed by mesoporous artificial enzymes


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Published on 24 May 2023
Thesis presented May 24, 2023

This thesis project was built around the principles of artificial metalloenzymes and heterogeneous catalysis. In an attempt to fill the gap in the development of abiotic reactions catalysed by artificial metalloenzymes, we aimed at the design of a series of artificial metalloenzymes with distinct and interesting catalytic activities: alkene epoxidation, CO2 cycloaddition leading to the design of a dual-site artificial metalloenzyme for cascade transformations.
Moreover, we ambitioned to exploit the protein environment in order to induce chirality throughout our investigations on alkene epoxidation. Working on the protein NikA, we have successfully reported a series of artificial epoxidases based on two distinct preparation modes. The first one relied on the supramolecular interactions with the native cavity of NikA. The second was based on covalent modification of a cysteine inserted in NikA through a Michael addition. This led to the development of five artificial epoxidases that displayed interesting activities with peracetic acid and Mukayama aerobic epoxidation. Interestingly, our investigations have put to light the influence of the artificial metalloenzymes preparation methodology on the stereoselectivity of the reaction. Indeed, optimization of anchoring assays led to an enantiomeric excess of 90% on the aerobic epoxidation of cis-β-methylstyrene with the NikA mutant H416C associated to a modified Mn(salen) ligand. Working on the same protein scaffold, associated with a covalently linked Co(salen) complex have led to the production of a new ArM for CO2 cycloaddition that was efficient under quite mild conditions. Associating this complex with an epoxidation complex on a single NikA mutant has allowed the creation of a dual-site ArM able to perform a cascade transformation to form cyclic carbonates from styrene through and epoxidation-CO2 cycloaddition reaction. This dual-site ArM was proven to be active and stable for up to five runs.
Although further optimization is needed, this project has paved the way of ArM design from the NikA protein through a novel anchoring methodology, via covalent modification, orthogonal to the characteristic supramolecular anchoring mode of NikA’s binding cavity.

NikAGARA, artificial metalloenzymes, heterogeneous catalysis, abiotic reaction, alkene epoxidation, CO2 cycloaddition, protein NikA

On-line thesis.