Synthetic Modeling of Mono-Iron Hydrogenase (Hmd): Utility of Anthracene Scaffold to Emulate the Facial Geometry of the Enzyme Active site
소속 :
연사 : Prof. Jun Hyeok Seo(GIST)
일시 : 2018-05-24 16:30 ~
장소 : 500동, 목암홀
Hydrogenases are metalloenzymes that involve energy metabolism in microbial communities as catalyzing the reversible oxidation of molecular hydrogen. The enzyme family is classified into three kinds, [FeFe]-, [NiFe]-, and [Fe]-hydrogenase. The dinuclear [FeFe], [NiFe]-hydrogenases have been studied in detail about their redox activity in the H2 generation and metabolism. Unlike the dinuclear hydrogenases, the third hydrogenase, mono-[Fe] hydrogenase, remains less studied. The enzyme catalyzes reversible conversion of methenyl-H4MPT+ to methylene-H4MPT during the methanogenic CO2 conversion as promoting the heterolytic splitting of H2. In aspect of the structure, the active site contains an Fe-ligating pyridone cofactor and another ligands of cysteine, two carbonyls and solvent in an octahedral geometry. The acyl-C, N donor in the pyridone ligand compose a facial coordination geometry together with the cysteine-S donor. We investigate the structural and functional relationship of the [Fe]-hydrogenase active site by synthesizing the model complexes.
In recent progress, we realized the facial coordination geometry is a key to demonstrate the enzyme-like reactivity using synthetic model complexes. The C, N, S donors set in the facial geometry enforces a substrate binding site to place in trans to the Fe-C sigma donor. While the Lewis acidic Fe(II) center and the H4MPT+ split the molecular hydrogen, the acyl-C adjusts the Lewis acidity of Fe(II) ion to transfer hydride to H4MPT+ efficiently. In experimental comparisons with another model complex in a meridional coordination geometry, only the facial geometry model showed the enzyme-like reactivity, heterolytic splitting of H2 and the hydride transfer. We understand a role of the facial geometry in the active site is to control the substrate (H2, methylene-H4MPT) interaction site to be placed in trans position to the Fe-acyl organometallic sigma bond. In the seminar, I will present a synthetic strategy using anthracene scaffold to construct our model complexes in the necessary facial coordination geometry, and additionally discuss the enzyme-like reactivities of the synthetic models towards molecular hydrogen and other substrates.
In recent progress, we realized the facial coordination geometry is a key to demonstrate the enzyme-like reactivity using synthetic model complexes. The C, N, S donors set in the facial geometry enforces a substrate binding site to place in trans to the Fe-C sigma donor. While the Lewis acidic Fe(II) center and the H4MPT+ split the molecular hydrogen, the acyl-C adjusts the Lewis acidity of Fe(II) ion to transfer hydride to H4MPT+ efficiently. In experimental comparisons with another model complex in a meridional coordination geometry, only the facial geometry model showed the enzyme-like reactivity, heterolytic splitting of H2 and the hydride transfer. We understand a role of the facial geometry in the active site is to control the substrate (H2, methylene-H4MPT) interaction site to be placed in trans position to the Fe-acyl organometallic sigma bond. In the seminar, I will present a synthetic strategy using anthracene scaffold to construct our model complexes in the necessary facial coordination geometry, and additionally discuss the enzyme-like reactivities of the synthetic models towards molecular hydrogen and other substrates.
