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Combining acid–base, redox and substrate binding functionalities to give a complete model for the [FeFe]-hydrogenase



Some enzymes function by coupling substrate turnover with electron transfer from a redox cofactor such as ferredoxin. In the [FeFe]-hydrogenases, nature's fastest catalysts for the production and oxidation of H2, the one-electron redox by a ferredoxin complements the one-electron redox by the diiron active site. In this Article, we replicate the function of the ferredoxins with the redox-active ligand Cp*Fe(C5Me4CH2PEt2) (FcP*). FcP* oxidizes at mild potentials, in contrast to most ferrocene-based ligands, which suggests that it might be a useful mimic of ferredoxin cofactors. The specific model is Fe2[(SCH2)2NBn](CO)3(FcP*)(dppv) (1), which contains the three functional components of the active site: a reactive diiron centre, an amine as a proton relay and, for the first time, a one-electron redox module. By virtue of the synthetic redox cofactor, [1]2+ exhibits unique reactivity towards hydrogen and CO. In the presence of excess oxidant and base, H2 oxidation by [1]2+ is catalytic.

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Figure 1: Structure of active site for the [FeFe]-hydrogenase and its model.
Figure 2: Synthesis of FcP*.
Figure 3: Summary of reactions observed for [1]2+ with CO and H2.
Figure 4: Infrared spectra probing the localization of the two one-electron oxidations of the reduced model [1].
Figure 5: Spectroscopic evidence confirming the reactions of [1]2+ with known hydrogenase substrates H2 and CO.


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This research was supported by the National Institutes of Health. The authors thank M. Nilges for assistance with EPR and M. Olsen for helpful discussions.

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All experiments were conducted by J.M.C., with input from T.B.R. The manuscript was written jointly by T.B.R. and J.M.C.

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Correspondence to Thomas B. Rauchfuss.

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The authors declare no competing financial interests.

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Camara, J., Rauchfuss, T. Combining acid–base, redox and substrate binding functionalities to give a complete model for the [FeFe]-hydrogenase. Nature Chem 4, 26–30 (2012).

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