Mono-iron Hydrogenase Research Articles

Bioinspired Design and Computational Prediction of SCS Nickel Pincer Complexes for Hydrogenation of Carbon Dioxide

Inspired by the structures of the active site of lactate racemase and H2 activation mechanism of mono-iron hydrogenase, we proposed a series of sulphur–carbon–sulphur (SCS) nickel complexes and computationally predicted their potentials for catalytic hydrogenation of CO2. Density functional theory calculations reveal a metal–ligand cooperated mechanism with the participation of a sulfur atom in the SCS pincer ligand as a proton receiver for the heterolytic cleavage of H2. For all newly proposed complexes containing functional groups with different electron-donating and withdrawing abilities in the SCS ligand, the predicted free energy barriers for the hydrogenation of CO2 to formic acid are in a range of 22.2–25.5 kcal/mol in water. Such a small difference in energy barriers indicates limited contributions of those functional groups to the charge density of the metal center. We further explored the catalytic mechanism of the simplest model complex for hydrogenation of formic acid to formaldehyde and obtained a total free energy barrier of 34.6 kcal/mol for the hydrogenation of CO2 to methanol.

CNS and CNP Iron(II) Mono-Iron Hydrogenase (Hmd) Mimics: Role of Deprotonated Methylene(acyl) and the trans-Acyl Site in H2 Heterolysis.

We report syntheses and H2 activation involving model complexes of mono-iron hydrogenase (Hmd) derived from acyl-containing pincer ligand precursors bearing thioether (CNSPre) or phosphine (CNPPre) donor sets. Both complexes feature pseudo-octahedral iron(II) dicarbonyl units. While the CNS pincer adopts the expected mer-CNS (pincer) geometry, the CNP ligand unexpectedly adopts the fac-CNP coordination geometry. Both complexes exhibit surprisingly acidic methylene C-H bond (reversibly de/protonated by a bulky phenolate), which affords a putative dearomatized pyridinate-bound intermediate. Such base treatment of Fe-CNS also results in deligation of the thioether sulfur donor, generating an open coordination site trans from the acyl unit. In contrast, Fe-CNP maintains a CO ligand trans from the acyl site both in the parent and dearomatized complexes (the -PPh2 donor is cis to acyl). The dearomatized mer-Fe-CNS was competent for H2 activation (5 atm D2(g) plus phenolate as base), which is attributed to both the basic site on the ligand framework and the open coordination site trans to the acyl donor. In contrast, the dearomatized fac-Fe-CNP was not competent for H2 activation, which is ascribed to the blocked coordination site trans from acyl (occupied by CO ligand). These results highlight the importance of both (i) the open coordination site trans to the organometallic acyl donor and (ii) a pendant base in the enzyme active site.

Computational prediction of pentadentate iron and cobalt complexes as a mimic of mono-iron hydrogenase for the hydrogenation of carbon dioxide to methanol.

A series of amidate-ligated pentadentate iron and cobalt complexes with N-heterocyclic pyridinol groups were proposed and computationally screened as potential catalysts for CO2 reduction. Density functional theory calculations reveal a ligand assisted heterolytic H2 cleavage mechanism with a total free energy barrier of 23.3 kcal mol-1 for the hydrogenation of CO2 to methanol catalysed by a pentadentate Co complex with a 2-[bis(pyridine-2-ylmethyl)]amino-N-3,9-purin-2-one ligand.

Effects of Thiolate Ligation in Monoiron Hydrogenase (Hmd): Stability of the {Fe(CO)2}2+ Core with NNS Ligands.

In this work, we report the effects of NNS-thiolate ligands and nuclearity (monomer, dimer) on the stability of iron complexes related to the active site of monoiron hydrogenase (Hmd). A thermally stable iron(II) dicarbonyl motif is the core feature of the active site, but the coordination features that lead to this property have not been independently evaluated for their contributions to the {Fe(CO)2}2+ stability. As such, non-bulky and bulky benzothiazoline ligands (thiolate precursors) were synthesized and their iron(II) complexes characterized. The use of non-bulky thiolate ligands and low-temperature crystallizations result in isolation of the dimeric species [(NNS)2Fe2(CO)2(I)2] (1), [(NPhNS)2Fe2(CO)2(I)2] (2), and [(MeNNS)2Fe2(CO)2(I)2] (3), which exhibit dimerization via thiolato (μ2-S)2 bridges. In one particular case (unsubstituted NNS ligand), the pathway of decarbonylation and oxidation from 1 was crystallographically elucidated, via isolation of the half-bis-ligated monocarbonyl dimer [(NNS)3Fe2(CO)]I (4) and the fully decarbonylated and oxidized mononuclear [(NNS)2Fe]I (5). The transformations of dicarbonyl complexes (1, 2, and 3) to monocarbonyl complexes (4, 6, and 7) were monitored by UV/vis, demonstrating that 1 and 3 exhibit longer t1/2 (80 and 75 min, respectively) than 2 (30 min), which is attributed to distortion of the ligand backbone. Density functional theory calculations of isolated complexes and putative intermediates were used to corroborate the experimentally observed IR spectra. Finally, dimerization was prevented using a bulky ligand featuring a 2,6-dimethylphenyl substituent, which affords mononuclear iron dicarbonyl complex, [(NPhNSDMPh)Fe(CO)2Br] (8), identified by IR and NMR spectroscopies. The dicarbonyl complex decomposes to the decarbonylated [(NPhNSDMPh)2Fe] (9) within minutes at room temperature. Overall, the work herein demonstrates that the thiolate moiety does not impart thermal stability to the {Fe(CO)2}2+ unit formed in the active site, further indicating the importance of the organometallic Fe-C(acyl) bond in the enzyme.

Dioxygen Sensitivity of [Fe]-Hydrogenase in the Presence of Reducing Substrates.

Mono-iron hydrogenase ([Fe]-hydrogenase) reversibly catalyzes the transfer of a hydride ion from H2 to methenyltetrahydromethanopterin (methenyl-H4 MPT+ ) to form methylene-H4 MPT. Its iron guanylylpyridinol (FeGP) cofactor plays a key role in H2 activation. Evidence is presented for O2 sensitivity of [Fe]-hydrogenase under turnover conditions in the presence of reducing substrates, methylene-H4 MPT or methenyl-H4 MPT+ /H2 . Only then, H2 O2 is generated, which decomposes the FeGP cofactor; as demonstrated by spectroscopic analyses and the crystal structure of the deactivated enzyme. O2 reduction to H2 O2 requires a reductant, which can be a catalytic intermediate transiently formed during the [Fe]-hydrogenase reaction. The most probable candidate is an iron hydride species; its presence has already been predicted by theoretical studies of the catalytic reaction. The findings support predictions because the same type of reduction reaction is described for ruthenium hydride complexes that hydrogenate polar compounds.

Functional Hydride Transfer by a Thiolate-Containing Model of Mono-Iron Hydrogenase featuring an Anthracene Scaffold.

We report the synthesis, X-ray structure and functional biomimetic activity of a model complex of mono-iron hydrogenase (Hmd). To achieve the desired biomimetic fac-CNS(thiolate) ligation motif, an anthracene framework is used to provide the requisite donors in a single chelate. A bulky aryl thiolate (ortho dimethylphenyl) is included to achieve mononuclearity. In addition to exhibiting structural (X-ray) and spectroscopic (NMR, IR) similarity to the enzyme, the complex is competent for H2 activation (heterolysis) and hydride transfer to a model substrate-mimicking the functional behavior of the enzyme in a biomimetic CNS coordination sphere for the first time.

Structural and functional synthetic model of mono-iron hydrogenase featuring an anthracene scaffold.

Mono-iron hydrogenase was the third type of hydrogenase discovered. Its Lewis acidic iron(II) centre promotes the heterolytic cleavage of the H-H bond and this non-redox H2 activation distinguishes it from the well-studied dinuclear [FeFe] and [NiFe] hydrogenases. Cleavage of the H-H bond is followed by hydride transfer to the enzyme's organic substrate, H4MPT+, which serves as a CO2 'carrier' in methanogenic pathways. Here we report a scaffold-based synthetic approach by which to model mono-iron hydrogenase using an anthracene framework, which supports a biomimetic fac-C,N,S coordination motif to an iron(II) centre. This arrangement includes the biomimetic and organometallic Fe-C σ bond, which enables bidirectional activity reminiscent of the native enzyme: the complex activates H2 under mild conditions, and catalyses C-H hydride abstraction plus H2 generation from a model substrate. Notably, neither H2 activation nor C-H hydride abstraction was observed in the analogous complex with a pincer-type mer-C,N,S ligation, emphasizing the importance of the fac-C,N,S-iron(II) motif in promoting enzyme-like reactivity.

Iron Hydride Detection and Intramolecular Hydride Transfer in a Synthetic Model of Mono-Iron Hydrogenase with a CNS Chelate.

We report the identification and reactivity of an iron hydride species in a synthetic model complex of monoiron hydrogenase. The hydride complex is derived from a phosphine-free CNS chelate that includes a Fe-C(NH)(═O) bond (carbamoyl) as a mimic of the active site iron acyl. The reaction of [((O═)C(HN)N(py)S(Me))Fe(CO)2(Br)] (1) with NaHBEt3 generates the iron hydride intermediate [((O═)C(HN)N(py)S(Me))Fe(H)(CO)2] (2; δFe-H = -5.08 ppm). Above -40 °C, the hydride species extrudes CH3S(-) via intramolecular hydride transfer, which is stoichiometrically trapped in the structurally characterized dimer μ2-(CH3S)2-[((O═)C(HN)N(Ph))Fe(CO)2]2 (3). Alternately, when activated by base ((t)BuOK), 1 undergoes desulfurization to form a cyclometalated species, [((O═)C(NH)NC(Ph))Fe(CO)2] (5); derivatization of 5 with PPh3 affords the structurally characterized species [((O═)C(NH)NC)Fe(CO)(PPh3)2] (6), indicating complex 6 as the common intermediate along each pathway of desulfurization.

Oxygen Coordination to the Active Site of Hmd in Relation to [FeFe] Hydrogenase

AbstractThe application of [FeFe] hydrogenases for renewable energy production is limited by the generally high O2‐sensitivity of this class of enzymes. In this work, we report energy differences in oxygen coordination at the active sites of [FeFe] and monoiron (Hmd) hydrogenase as obtained from DFT calculations. Whereas O2 addition is clearly exothermic in the case of [FeFe] hydrogenase, it is endothermic for monoiron hydrogenase. By applying a recently proposed concept [Inorg. Chem. 2010, 49, 5818], which allows us to structurally and electronically relate the two active sites, we show that an inversion in oxygen affinity is observed as a result of mutually exchanging the first ligand sphere of the central iron atoms of both catalytic centers. Modified Hmd active sites can bind O2 exothermically, whereas O2 addition to the altered H‐cluster variants is less exothermic than in the wild‐type configuration. Our results show that oxygen affinity is not very strong when measured in terms of the coordination energy. Hence, changes in the first ligand shell of the reactive iron atoms with retention of the similarity of the ligand spheres, that is, having the same type of ligands in the same positions of the coordination octahedron, can render oxygen coordination endo‐ or exothermic. This observation could explain the difference in oxygen sensitivity of Hmd and [FeFe] hydrogenases.

Analysis of a Pentacoordinate Iron Dicarbonyl as Synthetic Analogue of the Hmd or Mono‐Iron Hydrogenase Active Site

Pentacoordinate iron dicarbonyls, (NS)Fe(CO)(2)P (NS=2-amidothiophenylate, P=PCy(3) (4), PPh(3), (5), and P(OEt)(3) (6)) were prepared as potential biomimetics of the active site of the mono-iron hydrogenase, [Fe]-H(2)ase. Full characterization including X-ray diffraction, density functional theory (DFT) computations, and Mössbauer studies for complexes 5 and 6 find that, despite similar infrared v(CO) pattern and absorption frequencies as the active site of the [Fe]-H(2)ase, the geometrical distortions towards trigonal bipyramidal, the negative isomer shift parameters, and the differences in CO-uptake reactivity are due to the "non-innocence" of the NS ligand. Ligand-based protonation with a strong acid, HBF(4).Et(2)O, interrupted the extensive pi-delocalization over Fe and NS ligand of complex 4 and switched on CO uptake (1 bar) to form a CO adduct, mer-[(H-NS)Fe(CO)(3)(PCy(3))](+) or 4(CO)-H(+). The extrinsic CO is reversibly removed on deprotonation with Et(3)N to regenerate complex 4. In a (13)CO atmosphere, concomitant CO uptake by 4-H(+) and exchange with intrinsic CO groups provide a facile route to (13)C-labeled 4(CO)-H(+) and, upon deprotonation, (13)C-labeled complex 4. DFT calculations show substantial Fe character in the LUMO of 4-H(+) typical of the d(6) Fe(II) in a regular square-pyramidal geometry. Thus, the Lewis acidity of 4-H(+) makes it amenable for CO binding, whereas the dianionic NS ligand renders the iron center of 4 insufficiently electrophilic and largely of Fe(I) character.

Synthesis and Mössbauer Characterization of Octahedral Iron(II) Carbonyl Complexes FeI2(CO)3L and FeI2(CO)2L2: Developing Models of the [Fe]-H2ase Active Site

A series of mono- and disubstituted complexes, FeI(2)(CO)(x)L(4-x), x = 2 or 3, is conveniently accessed from simple mixing of N-heterocyclic carbenes, phosphines, and aromatic amines with FeI(2)(CO)(4), first reported by Hieber in 1928. The highly light sensitive complexes yield to crystallization and X-ray diffraction studies for six complexes showing them to be rudimentary structural models of the monoiron hydrogenase, [Fe]-H(2)ase or Hmd, active site in native (Fe(II)(CO)(2)) or CO-inhibited (Fe(II)(CO)(3)) states. Diatomic ligand (nu(CO)) vibrational and Mossbauer spectroscopies are related to those reported for the Hmd active site. The importance of a serial approach for relating such parameters in model compounds to low spin Fe(II) in the diverse ligation of enzyme active sites is stressed.

Trigger Mechanism for the Catalytic Hydrogen Activation by Monoiron (Iron−Sulfur Cluster-Free) Hydrogenase

A fully optimized model for the resting state of the active site of the third type of phylogenetically unrelated (monoiron) hydrogenase, iron-sulfur cluster-free hydrogenase (Hmd), was constructed based on density functional calculations. This resting state structure shows good agreement with the experimental IR spectra. The calculations predict that the barrier for H2 cleavage in the presence of MPT+ is 18 kcal/mol lower than that in the absence of MPT+, a result that explains why the isotopic H2/D2O exchange catalyzed by Hmd is strictly dependent on the presence of MPT+. This difference is a result of the MPT+ triggering the pyridone to provide electron density to allow the Fe to take a proton while transferring a hydride to the MPT+. These active site models and catalytic mechanism are useful in understanding this hydrogen activation for the design of novel hydrogenation catalysts and for low cost, high efficiency hydrogen generation.