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Abstract Native metalloenzymes are unparalleled in their ability to perform efficient small molecule activation reactions, converting simple substrates into complex products. Most of these natural systems possess multiple metallocofactors to facilitate electron transfer or cascade catalysis. While the field of artificial metalloenzymes is growing at a rapid rate, examples of artificial enzymes that leverage two distinct cofactors remain scarce. In this work, we describe a new class of artificial enzymes containing two different metallocofactors, incorporated through bioorthogonal strategies. Nickel-substituted rubredoxin (Ni^Rd), which is a structural and functional mimic of [NiFe] hydrogenases, is used as a scaffold. Incorporation of a synthetic bimetallic inorganic complex based on a macrocyclic biquinazoline ligand (M^MBQ) was accomplished using a novel chelating thioether linker. Neither the structure of the Ni^Rdactive site nor the M^MBQwere altered upon attachment, and each site retained independent redox activity. Electrocatalysis was observed from each site, with the switchability of the system demonstrated through the use of catalytically inert metal centers. This M^MBQ–Ni^Rdplatform offers a new avenue to create multicofactor artificial metalloenzymes in a robust system that can be easily tuned both through modifications to the protein scaffold and the synthetic moiety, with applications for redox catalysis and tandem reactivity. Graphical abstract 

Abstract Biological N₂reduction occurs at sulfur‐rich multiiron sites, and an interesting potential pathway is concerted double reduction/ protonation of bridging N₂through PCET. Here, we test the feasibility of using synthetic sulfur‐supported diiron complexes to mimic this pathway. Oxidative proton transfer from μ‐η¹ : η¹‐diazene (HN=NH) is the microscopic reverse of the proposed N₂fixation pathway, revealing the energetics of the process. Previously, Sellmann assigned the purple metastable product from two‐electron oxidation of [{Fe²⁺(PPr₃)L¹}₂(μ‐η¹ : η¹‐N₂H₂)] (L¹=tetradentate SSSS ligand) at −78 °C as [{Fe²⁺(PPr₃)L¹}₂(μ‐η¹ : η¹‐N₂)]²⁺, which would come from double PCET from diazene to sulfur atoms of the supporting ligands. Using resonance Raman, Mössbauer, NMR, and EPR spectroscopies in conjunction with DFT calculations, we show that the product is not an N₂complex. Instead, the data are most consistent with the spectroscopically observed species being the mononuclear iron(III) diazene complex [{Fe(PPr₃)L¹}(η²‐N₂H₂)]⁺. Calculations indicate that the proposed double PCET has a barrier that is too high for proton transfer at the reaction temperature. Also, PCET from the bridging diazene is highly exergonic as a result of the high Fe^3+/2+redox potential, indicating that the reverse N₂protonation would be too endergonic to proceed. This system establishes the “ground rules” for designing reversible N₂/N₂H₂interconversion through PCET, such as tuning the redox potentials of the metal sites.