An Artificial Enzyme Made by Covalent Grafting of an FeII Complex into β‐Lactoglobulin: Molecular Chemistry, Oxidation Catalysis, and Reaction‐Intermediate Monitoring in a Protein

Abstract An artificial metalloenzyme based on the covalent grafting of a nonheme Fe II polyazadentate complex into bovine β‐lactoglobulin has been prepared and characterized by using various spectroscopic techniques. Attachment of the Fe II catalyst to the protein scaffold is shown to occur specifically at Cys121. In addition, spectrophotometric titration with cyanide ions based on the spin‐state conversion of the initial high spin ( S =2) Fe II complex into a low spin ( S =0) one allows qualitative and quantitative characterization of the metal center’s first coordination sphere. This biohybrid catalyst activates hydrogen peroxide to oxidize thioanisole into phenylmethylsulfoxide as the sole product with an enantiomeric excess of up to 20 %. Investigation of the reaction between the biohybrid system and H 2 O 2 reveals the generation of a high spin ( S =5/2) Fe III (η 2 ‐O 2 ) intermediate, which is proposed to be responsible for the catalytic sulfoxidation of the substrate.