Controlling radical-type transformations in aqueous medium with artificial metalloenzymes
Radical type nitrene transfer reactions are a powerful tool for the direct functionalization of C-H bonds and olefins. For instance, the synthesis of aziridines typically requires harsh conditions and multiple steps, but can be achieved directly and under mild conditions with N-group transfer reactions. The presence of these moieties in antitumor and antibiotic drugs, makes such reaction products of great value. Generally, nitrene transfer catalysis is carried out in organic solvents. However, water is considered an ideal reaction medium for radical-type transformations, given the high bond dissociation energy of the H-OH bond. Furthermore, successful performance of these reactions in water could provide a more environmentally friendly procedure and opens doors for novel applications such as in vivo pro-drug activation. However, nitrene transfer catalysis tends to suffer from unwanted side reactions in aqueous medium, which hampers future applications. In this collaborative project, we aim to encapsulate a cobalt-catalyst in the hydrophobic cavity of a protein host, via the ‘Biotin-Streptavidin Technique’, to prevent undesired side-reactivity. Therefore, the goal of this project is to synthesize and characterize an artificial metalloenzyme, and to study its catalytic activity in radical-type nitrene transfer catalysis in aqueous medium.