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

Journal name:
Nature Chemistry
Volume:
9,
Pages:
552–557
Year published:
DOI:
doi:10.1038/nchem.2707
Received
Accepted
Published online

Abstract

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.

At a glance

Figures

  1. Comparison of enzyme active site and model complexes.
    Figure 1: Comparison of enzyme active site and model complexes.

    a, Active site of mono-iron hydrogenase8, highlighting the facial arrangement of ligands (blue and maroon), and including a proposed mechanism of H2 activation. b, The target ‘anthracene scaffold’ complex and our previously reported synthetic model (note: the present model complex uses a thioether-S donor to model the Cys176-thiolate)13.

  2. Synthesis and DFT-optimized structure of compound 1, and the structure of 2 determined by X-ray crystallography.
    Figure 2: Synthesis and DFT-optimized structure of compound 1, and the structure of 2 determined by X-ray crystallography.

    a, Synthesis of the anthracene-based ligand Anth•NH2Py•S and its iron carbamoyl derivative 1. b, The DFT calculated, geometry optimized structure of 1 (PW91/6-31G**, except for iodine, 6-311G**). c, Molecular structure (50% thermal ellipsoids) for the PPh3 derivative of 1, namely [(Anth•CNHNS)Fe(CO)2(PPh3)(I)] (2); hydrogen atoms are omitted and PPh3 is truncated for clarity. Selected bond distances (Å): Fe1–C1, 1.933(5); Fe1–C46, 1.814(5); Fe1–C47, 1.881(7); Fe1–N2, 2.008(4); Fe1–I1, 2.689(8); Fe1–P1, 2.335(14).

  3. C–H hydride abstraction from imidazolidine and H2 evolution mediated by complex 3.
    Figure 3: C–H hydride abstraction from imidazolidine and H2 evolution mediated by complex 3.

    Generation of the THF-solvato complex 3 by halide removal from 1 with [Tl](BArF), and its hydride abstraction reactivity from 1,3-bis(2,6-difluorophenyl)-2-(p-tolyl)imidazolidine (Im–H) to afford the corresponding imidazolium (Im+) and the Fe–H species 4. Intermediate 4 proceeds to form H2 via hydride transfer to a non-coordinating proton source (2,6-di-tert-butyl-4-methoxyphenol).

  4. Hydride abstraction from imidazolidine by complex 3 monitored by 1H NMR.
    Figure 4: Hydride abstraction from imidazolidine by complex 3 monitored by 1H NMR.

    Series of 1H NMR spectra for stoichiometric hydride abstraction from 1,3-bis(2,6-difluorophenyl)-2-(p-tolyl)imidazolidine (Im–H) by complex 3 in d8-THF at 25 °C, where the Im–H methine C–H peak at 6.12 ppm decreases over the course of the reaction.

  5. D2 gas activation by complex 3 evidenced by NH → ND exchange in complex 3.
    Figure 5: D2 gas activation by complex 3 evidenced by NH → ND exchange in complex 3.

    a, 2H NMR spectrum indicating the formation of [(Anth•CNDNS)Fe(CO)2(THF)](BArF) (3D) from 3 in THF under 1 atm D2 at 25 °C over t ≈ 2 h. b, Timecourse of NH → ND exchange (1, 3, 6, 20 and 21 days) observed under 1 atm of mixed H2/D2 (1:1) at 25 °C.

  6. Deuteride (D−) transfer from D2 to H+ and formation of Fe–D species.
    Figure 6: Deuteride (D) transfer from D2 to H+ and formation of Fe–D species.

    a, Formation of 4 from 3 in THF under D2 atmosphere, and subsequent iron-mediated deuteride transfer to a proton source, thereby generating HD. b, 1H NMR spectrum indicating the presence of H2 and HD as scrambling products from D2/H+ as catalysed by 3; experimental conditions: 3, D2, dBPhOH in d8-THF. c, 2H NMR spectrum indicating the presence of the [Fe–D] species, 4; experimental conditions: 3D, D2, dBPhOD in THF.

Compounds

4 compounds View all compounds
  1. [(Anth·CNHNS)Fe(CO)2(I)]
    Compound 1 [(Anth·CNHNS)Fe(CO)2(I)]
  2. [(Anth·CNHNS)Fe(CO)2(I)(PPh3)]
    Compound 2 [(Anth·CNHNS)Fe(CO)2(I)(PPh3)]
  3. [(Anth·CNHNS)Fe(CO)2(THF)](BARF)
    Compound 3 [(Anth·CNHNS)Fe(CO)2(THF)](BARF)
  4. [(Anth·CNHNS)Fe(CO)2(H)]
    Compound 4 [(Anth·CNHNS)Fe(CO)2(H)]

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Author information

Affiliations

  1. Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, USA

    • Junhyeok Seo,
    • Taylor A. Manes &
    • Michael J. Rose

Contributions

M.J.R. and J.S. designed the experiments. J.S. synthesized and characterized the model complexes, and J.S. performed the experiments and analysed the data. M.J.R. and J.S. carried out the DFT calculations. J.S. and T.A.M. synthesized ligands. M.J.R. and J.S. co-wrote the paper.

Competing financial interests

The authors declare no competing financial interests.

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    Crystallographic data for compound 2.

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