Inaccessibility of the μ-hydride species in [FeFe] hydrogenases

Finkelmann, Arndt R.; Stiebritz, Martin T.; Reiher, Markus

doi:10.1039/c3sc51700d

Cited by 52 publications

(96 citation statements)

References 58 publications

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“…1,8,11,12,35 Past proposals for the catalytic mechanism can be divided into one set involving a bridging hydride between Fe p and Fe d 36 (Mechanism I as described by Trohalaki and Pachter 11 ) and another set involving a terminal hydride on Fe d (Mechanism II). 35 We see no evidence that H hyd involves a bridging hydride.…”

Section: Resultsmentioning

confidence: 99%

“…Other reports also disfavor bridging hydride-based mechanisms on a variety of grounds. 12,38 We thus consider the implications of the NRVS results on mechanisms involving a terminal hydride. For this case, a consensus has emerged that proton transfer from an −NH 2 + – form of the bridgehead nitrogen to Fe d hydride is the key step in H 2 formation.…”

Section: Resultsmentioning

confidence: 99%

“…4-6 Fe d , the site at which hydrogen binds, is the Lewis acid. 7,8 Many previous experimental and theoretical studies 9-12 implicate a Fe d -H h ⋯H A -N ADT species as the key intermediate leading to H-H bond formation (Figure 1A). Despite its mechanistic importance, however, experimental characterization of such HLH interactions in the enzyme has not been available so far.…”

Section: Introductionmentioning

confidence: 91%

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Reaction Coordinate Leading to H₂ Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory

et al. 2017

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[FeFe]-hydrogenases are metalloenzymes that reversibly reduce protons to molecular hydrogen at exceptionally high rates. We have characterized the catalytically competent hydride state (Hhyd) in the [FeFe]-hydrogenases from both Chlamydomonas reinhardtii and Desulfovibrio desulfuricans using 57Fe Nuclear Resonance Vibrational Spectroscopy (NRVS) and Density Functional Theory (DFT). H/D exchange identified two Fe-H bending modes originating from the binuclear iron cofactor. DFT calculations show that these spectral features result from an iron-bound terminal hydride, with the Fe-H vibrational frequencies being highly dependent on interactions between the amine base of the catalytic cofactor with both hydride and the conserved cysteine terminating the proton transfer chain to the active site. The results indicate that Hhyd is the catalytic state one step prior H2 formation. The observed vibrational spectrum, therefore, provides mechanistic insight into the reaction coordinate for H2 bond formation by [FeFe]-hydrogenases.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

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Reaction Coordinate Leading to H₂ Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory

et al. 2017

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“…Dissociation of a hydroxide anion is energetically even more unfavored (ΔE dissoc (4) = +86.2 kcal/mol and ΔE dissoc (80) = +55.6 kcal/mol). Note that in the product structure 77 Water formation would require a second proton transfer to the hydroxo ligand. Protonation of the bridgehead amine is exothermic by only −4.0 kcal/mol.…”

Section: Oxygen Coordination To Fe D and Subsequentmentioning

confidence: 99%

Activation Barriers of Oxygen Transformation at the Active Site of [FeFe] Hydrogenases

2014

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Oxygen activation at the active sites of [FeFe] hydrogenases has been proposed to be the initial step of irreversible oxygen-induced inhibition of these enzymes. On the basis of a first theoretical study into the thermodynamics of O2 activation [Inorg. Chem. 2009, 48, 7127] we here investigate the kinetics of possible reaction paths at the distal iron atom of the active site by means of density functional theory. A sequence of steps is proposed to either form a reactive oxygen species (ROS) or fully reduce O2 to water. In this reaction cascade, two branching points are identified where water formation directly competes with harmful oxygen activation reactions. The latter are water formation by O-O bond cleavage of a hydrogen peroxide-bound intermediate competing with H2O2 dissociation and CO2 formation by a putative iron-oxo species competing with protonation of the iron-oxo species to form a hydroxyo ligand. Furthermore, we show that proton transfer to activated oxygen is fast and that proton supply to the active site is vital to prevent ROS dissociation. If sufficiently many reduction equivalents are available, oxygen activation reactions are accelerated, and oxygen reduction to water becomes possible.

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“…20 In Nature, terminal-to-bridge isomerization is prevented by strong hydrogen bonding between the protein and at least one of the FeC N sites. 21 Although Fe–H species are likely intermediates in the biological mechanism, 5,16 they have not been confirmed in native enzymes.…”

Section: Acid–base Reactions Of Fe2(sr)2(co)6–xlxmentioning

confidence: 99%

Diiron Azadithiolates as Models for the [FeFe]-Hydrogenase Active Site and Paradigm for the Role of the Second Coordination Sphere

2015

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CONSPECTUS The [FeFe] hydrogenases (H2ases) catalyze the redox reaction that interconverts protons and H2. This area of biocatalysis has attracted attention because the metal-based chemistry is unusual, and the reactions have practical implications. The active site consists of a [4Fe–4S] cluster bridged to a [Fe2(μ-dithiolate)(CN)2(CO)3]z center (z = 1− and 2−). The dithiolate cofactor is [HN(CH2S)2]2−, called the azadithiolate ([adtH]2−). Although many derivatives of Fe2(SR)2(CO)6–xLx are electrocatalysts for the hydrogen evolution reaction (HER), most operate by slow nonbiomimetic pathways. Biomimetic hydrogenogenesis is thought to involve intermediates, wherein the hydride substrate is adjacent to the amine of the adtH, being bonded to only one Fe center. Formation of terminal hydride complexes is favored when the diiron carbonyl models contain azadithiolate. Although unstable in the free state, the adt cofactor is stable once it is affixed to the Fe2 center. It can be prepared by alkylation of Fe2(SH)2(CO)6 with formaldehyde in the presence of ammonia (to give adtH derivatives) or amines (to give adtR derivatives). Weak acids protonate Fe2(adtR)(CO)2(PR3)4 to give terminal hydrido (term-H) complexes. In contrast, protonation of the related 1,3-propanedithiolate (pdt2−) complexes Fe2(pdt)(CO)2(PR3)4 requires strong acids. The amine in the azadithiolate is a kinetically fast base, relaying protons to and from the iron, which is a kinetically slow base. The crystal structure of the doubly protonated model [(term-H)Fe2(HadtH)(CO)2(dppv)2]2+ confirms the presence of both ammonium and terminal hydrido centers, which interact through a dihydrogen bond (dppv = cis-C2H2(PPh2)2). DFT calculations indicate that this H---H interaction is sensitive to the counterions and is strengthened upon reduction of the diiron center. For the monoprotonated models, the hydride [(term-H)Fe2(adtH)(CO)2(dppv)2]+ exists in equilibrium with the ammonium tautomer [Fe2(HadtH)(CO)2(dppv)2]+. Both [(term-H)Fe2(HadtH)(CO)2(dppv)2]2+ and [(term-H)Fe2(adtH)(CO)2(dppv)2]+ are highly active electrocatalysts for HER. Catalysis is initiated by reduction of the diferrous center, which induces coupling of the protic ammonium center and the hydride ligand. In contrast, the propanedithiolate [(term-H)Fe2(pdt)(CO)2(dppv)2]+ is a poor electrocatalyst for HER. Oxidation of H2 has been demonstrated, starting with models for the oxidized state (“Hox”), for example, [Fe2(adtH)-(CO)3(dppv)(PMe3)]+. Featuring a distorted Fe(II)Fe(I) center, this Hox model reacts slowly with high pressures of H2 to give [(μ-H)Fe2(adtH)(CO)3(dppv)(PMe3)]+. Highlighting the role of the proton relay, the propanedithiolate [Fe2(pdt)-(CO)3(dppv)(PMe3)]+ is unreactive toward H2. The Hox-model + H2 reaction is accelerated in the presence of ferrocenium salts, which simulate the role of the attached [4Fe–4S] cluster. The redox-complemented complex [Fe2(adtBn)(CO)3(dppv)-(FcP*)]n+ catalyzes both proton reduction and hydrogen oxidation (FcP* = (C5Me5)Fe(C5Me4CH2PEt2)).

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Inaccessibility of the μ-hydride species in [FeFe] hydrogenases

Cited by 52 publications

References 58 publications

Reaction Coordinate Leading to H₂ Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory

Reaction Coordinate Leading to H₂ Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory

Activation Barriers of Oxygen Transformation at the Active Site of [FeFe] Hydrogenases

Diiron Azadithiolates as Models for the [FeFe]-Hydrogenase Active Site and Paradigm for the Role of the Second Coordination Sphere

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Inaccessibility of the μ-hydride species in [FeFe] hydrogenases

Cited by 52 publications

References 58 publications

Reaction Coordinate Leading to H2 Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory

Reaction Coordinate Leading to H2 Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory

Activation Barriers of Oxygen Transformation at the Active Site of [FeFe] Hydrogenases

Diiron Azadithiolates as Models for the [FeFe]-Hydrogenase Active Site and Paradigm for the Role of the Second Coordination Sphere

Contact Info

Product

Resources

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Reaction Coordinate Leading to H₂ Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory

Reaction Coordinate Leading to H₂ Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory