Anthracene-scaffolded model complexes of [Fe]-hydrogenase (Hmd) for improved functional reactivity and mechanistic investigations of biomimetic H₂ activation and hydride transfer




Kerns, Spencer Austin

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Abstract: The metalloenzyme [Fe]-hydrogenase (Hmd) is present in methanogenic archaea and catalyzes the activation of dihydrogen (H₂) and hydride (H⁻) transfer to its pterin-like substrate, methenyl-tetrahydromethanopterin (methenyl-H₄MPT⁺) to form methylene-tetrahydromethanopterin (methylene-H₄MPT). This reaction represents one of the steps in the assimilation of CO₂ to generate CH₄ performed by methanogens in Nature. The active site of [Fe]-hydrogenase is comprised of a pyridone cofactor-ligated mononuclear, redox-inactive ferrous site, cysteine ligation, and a cis dicarbonyl motif and has inspired synthetic model complexes as it: (i) features a highly asymmetric primary coordination sphere (ii) contains a unique, highly-substituted acylpyridone organic metal-binding cofactor (iii) contains the first stable organometallic metal-carbon [sigma] bond (Fe-C [subscript acyl]) that persists throughout catalysis in biology. Mechanistic intermediates of Hmd catalysis have been difficult to observe, and functional synthetic model systems that provide insight into the mechanistic understanding of [Fe]-hydrogenase are very limited. This work describes the utility of an anthracene molecular scaffold in the design of model complexes of [Fe]-hydrogenase to encourage precise, directed metal coordination motifs, to impart stability, and to enable functional reactivity studies. An anthracene-scaffolded carbamoyl thiolate complex was synthesized, characterized, and was demonstrated to activate to H₂ and perform the biomimetic hydride transfer reaction to a model substrate upon addition of exogenous base. Another anthracene-scaffolded acyl thioether complex was synthesized and characterized, and treatment with exogenous base resulted in deprotonation of a methylene proton of the acyl moiety. The deprotonated complex was structurally characterized and demonstrated to react with H₂; however, H₂ activation resulted in reduction of the metal center and extrusion of iron from the ligand initiated by iron hydride formation. The design and syntheses of an anthracene-scaffolded [Fe]-hydrogenase model complex for incorporation into a beta-lactoglobulin protein host are described, along with preliminary circular dichroism and fluorescence spectroscopy studies of ligand integration.



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