Hydrogen-activating models of hydrogenases

Hydrogenases are biological catalysts for hydrogen evolution and activation. While many model complexes of hydrogenases can catalyze the hydrogen evolution reaction, few of them can react with hydrogen. Here we review the hydrogen-activating models of hydrogenases, in particular, [NiFe]- and [FeFe]-hydrogenases. The mechanism of these reactions is described

[Fe]-hydrogenase and Models Containing An Iron-Acyl Ligation

[Fe]-hydrogenase is a newly characterized type of hydrogenase. This enzyme heterolytically splits hydrogen in the presence of a natural substrate. The active site of the enzyme contains a mono-iron complex with intriguing ironacyl ligation. Several groups have recently developed ironacyl complexes as synthetic models of [Fe]-hydrogenase. This Focus Review summarizes the studies of this enzyme and its model compounds, with an emphasis on our own research in this area

Synthesis and Reactivity of Mononuclear Iron Models of [Fe]-Hydrogenase that Contain an Acylmethylpyridinol Ligand

[Fe]-hydrogenase has a single iron-containing active site that features an acylmethylpyridinol ligand. This unique ligand environment had yet to be reproduced in synthetic models; however the synthesis and reactivity of a new class of small molecule mimics of [Fe]-hydrogenase in which a mono-iron center is ligated by an acylmethylpyridinol ligand has now been achieved. Key to the preparation of these model compounds is the successful C[BOND]O cleavage of an alkyl ether moiety to form the desired pyridinol ligand. Reaction of solvated complex [(2-CH2CO-6-HOC5H3N)Fe(CO)2(CH3CN)2]+(BF4)− with thiols or thiophenols in the presence of NEt3 yielded 5-coordinate iron thiolate complexes. Further derivation produced complexes [(2-CH2CO-6-HOC5H3N)Fe(CO)2(SCH2CH2OH)] and [(2-CH2CO-6-HOC5H3N)Fe(CO)2(CH3COO)], which can be regarded as models of FeGP cofactors of [Fe]-hydrogenase extracted by 2-mercaptoethanol and acetic acid, respectively. When the derivative complexes were treated with HBF4⋅Et2O, the solvated complex was regenerated by protonation of the thiolate ligands. The reactivity of several models with CO, isocyanide, cyanide, and H2 was also investigated

Reconstitution of [Fe]-hydrogenase using model complexes

[Fe]-Hydrogenase catalyses the reversible hydrogenation of a methenyltetrahydromethanopterin substrate, which is an intermediate step during the methanogenesis from CO2 and H-2. The active site contains an iron-guanylylpyridinol cofactor, in which Fe2+ is coordinated by two CO ligands, as well as an acyl carbon atom and a pyridinyl nitrogen atom from a 3,4,5,6-substituted 2-pyridinol ligand. However, the mechanism of H-2 activation by [Fe]-hydrogenase is unclear. Here we report the reconstitution of [Fe]-hydrogenase from an apoenzyme using two FeGP cofactor mimics to create semisynthetic enzymes. The small-molecule mimics reproduce the ligand environment of the active site, but are inactive towards H-2 binding and activation on their own. We show that reconstituting the enzyme using a mimic that contains a 2-hydroxypyridine group restores activity, whereas an analogous enzyme with a 2-methoxypyridine complex was essentially inactive. These findings, together with density functional theory computations, support a mechanism in which the 2-hydroxy group is deprotonated before it serves as an internal base for heterolytic H-2 cleavage

A Pyridinol Acyl Cofactor in the Active Site of [Fe]-hydrogenase Evidenced by the Reactivity of Model Complexes

The decomposition reaction of a water-soluble complex (see scheme; 1) in H2O confirms the existence of a unique bidentate pyridinol cofactor in [Fe]-hydrogenase. This unique moiety is confirmed for the first time by the decomposition of a well-defined model complex containing a pyridinyl methyl acyl ligand

[Fe]-Hydrogenase Models Featuring Acylmethylpyridinyl Ligands

The synthesis, structure, and reactivity of small-molecule models of [Fe]-hydrogenase are described. These models feature the intriguing acylmethylpyridinyl ligands found exclusively in the enzyme

A Five-Coordinate Iron Center in the Active Site of [Fe]-Hydrogenase: Hints from a Model Study

The synthesis, structure, and reactivity of a five-coordinate model complex of [Fe]-hydrogenase are described. The work suggests that the iron center in [Fe]-hydrogenases could be five-coordinate in the resting state

Reversible protonation of a thiolate ligand in an [Fe]-hydrogenase model complex

The thiolate ligand in the five-coordinate model complex 1 of [Fe]-hydrogenase is preferentially and reversibly protonated, even in the presence of an acyl ligand. The results suggest that the Cys176 thiolate ligand in [Fe]-hydrogenase can serve as the internal base to accept the proton after heterolytic splitting of H2