Integrated Computational Study of the Cu-Catalyzed Hydration of Alkenes in Water Solvent and into the Context of an Artificial Metallohydratase

Despite the increasing efforts in the last few years, the identification of efficient catalysts able to perform the enantioselective addition of water to double bonds has not been achieved yet. Natural hydratases represent an interesting pool of biocatalysts to generate chiral alcohols, but modifying their substrate scope remains an issue. The use of artificial metalloenzymes (ArMs) appears as a promising solution in this field. In the last few years, Roelfes and co-workers have been designing a variety of DNA- and protein-based ArMs able to carry out the copper-mediated addition of water to conjugated alkenes with promising enantioselective levels. Still, from a mechanistic point of view, the copper-mediated hydration reaction remains unclear and a matter of debate. This lack of information greatly hampers further designs and optimizations of the LmrR-based copper hydratases in terms of substrates and/or enantioselective profiles. In this study, we aim to provide a better understanding of the copper-cata...