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

Nature Chemistry volume 9, pages 552–557 (2017)Cite this article

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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.

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Figure 1: Comparison of enzyme active site and model complexes.
Figure 2: Synthesis and DFT-optimized structure of compound 1, and the structure of 2 determined by X-ray crystallography.
Figure 3: C–H hydride abstraction from imidazolidine and H2 evolution mediated by complex 3.
Figure 4: Hydride abstraction from imidazolidine by complex 3 monitored by 1H NMR.
Figure 5: D2 gas activation by complex 3 evidenced by NH → ND exchange in complex 3.
Figure 6: Deuteride (D−) transfer from D2 to H+ and formation of Fe–D species.

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Acknowledgements

This research was supported by the Welch Foundation (F-1822) and the ACS Petroleum Research Fund (53542-DN13), as well as the UT College of Natural Sciences. We also thank V. Lynch for assistance with X-ray data analysis, and S. Sorey for assistance with NMR study.

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Authors and Affiliations

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

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

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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.

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Correspondence to Michael J. Rose.

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The authors declare no competing financial interests.

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Crystallographic data for compound 2. (CIF 1275 kb)

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Seo, J., Manes, T. & Rose, M. Structural and functional synthetic model of mono-iron hydrogenase featuring an anthracene scaffold. Nature Chem 9, 552–557 (2017). https://doi.org/10.1038/nchem.2707

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