Dafa Chen

[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.

Synthesis and Reactivity of Iron Acyl Complexes Modeling the Active Site of [Fe]-Hydrogenase

A [Fe(II)Fe(II)] dithiolate complex containing acyl and carbonyl ligands was synthesized. The diiron complex reacted with phosphine, cyanide, isocyanide, and CO to give monomeric Fe(II) complexes reproducing the first coordination sphere of the active site of [Fe]-hydrogenase (H(2)-forming methylene-tetrahydromethanopterin dehydrogenase, Hmd) in various states. All the acyl and carbonyl carbons in the diiron complex underwent facile isotopic exchange with (13)CO via monomeric Fe tricarbonyl intermediates.

An Iron Carbonyl Pyridonate Complex Related to the Active Site of the [Fe]-Hydrogenase (Hmd)

A mononuclear iron bis(carbonyl) pyridonate complex (1), which exhibits several common structural features with the active site of the iron-sulfur cluster-free [Fe]-hydrogenase, was synthesized and characterized. Spectroscopic data of 1 suggests a 2+ oxidation state for the Fe ion in the [Fe]-hydrogenase. Complex 1 serves as a precursor to other hydrogenase models.

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.

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-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.

Synthesis and characterization of a series of model complexes of the active site of [Fe]-hydrogenase (Hmd).

A series of Fe complexes were synthesized and characterized as small molecule mimics for the active site of [Fe]-hydrogenase (Hmd). The collection includes both structurally new compounds and analogues of previously reported models. These complexes contain the essential ligands of the enzyme, namely, acyl, CO, pyridone, and sulfur ligands. They serve as IR and Mössbauer spectroscopic models for the Fe center in [Fe]-hydrogenase. The field-dependent Mössbauer study of representative model complexes shows that the sign and absolute value of the quadrupole splitting are sensitive to the change in the ligand environment of the Fe center.

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 H2. The active site contains an iron-guanylylpyridinol cofactor, in which Fe(2+) 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 H2 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 H2 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 H2 cleavage.

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

Understanding the complex: The decomposition reaction of a water-soluble complex (see scheme; 1) in H(2)O 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.

Reversible Dimerization of Mononuclear Models of [Fe]-Hydrogenase

Enzyme models on the catwalk! A series of new model complexes of the active site of [Fe]-hydrogenase have been synthesized and characterized. These complexes are monomeric in solution, but dimeric in the solid state.