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Structure and reactivity of a mononuclear non-haem iron(III)–peroxo complex

Abstract

Oxygen-containing mononuclear iron species—iron(iii)–peroxo, iron(iii)–hydroperoxo and iron(iv)–oxo—are key intermediates in the catalytic activation of dioxygen by iron-containing metalloenzymes1,2,3,4,5,6,7. It has been difficult to generate synthetic analogues of these three active iron–oxygen species in identical host complexes, which is necessary to elucidate changes to the structure of the iron centre during catalysis and the factors that control their chemical reactivities with substrates. Here we report the high-resolution crystal structure of a mononuclear non-haem side-on iron(iii)–peroxo complex, [Fe(iii)(TMC)(OO)]+. We also report a series of chemical reactions in which this iron(iii)–peroxo complex is cleanly converted to the iron(iii)–hydroperoxo complex, [Fe(iii)(TMC)(OOH)]2+, via a short-lived intermediate on protonation. This iron(iii)–hydroperoxo complex then cleanly converts to the ferryl complex, [Fe(iv)(TMC)(O)]2+, via homolytic O–O bond cleavage of the iron(iii)–hydroperoxo species. All three of these iron species—the three most biologically relevant iron–oxygen intermediates—have been spectroscopically characterized; we note that they have been obtained using a simple macrocyclic ligand. We have performed relative reactivity studies on these three iron species which reveal that the iron(iii)–hydroperoxo complex is the most reactive of the three in the deformylation of aldehydes and that it has a similar reactivity to the iron(iv)–oxo complex in C–H bond activation of alkylaromatics. These reactivity results demonstrate that iron(iii)–hydroperoxo species are viable oxidants in both nucleophilic and electrophilic reactions by iron-containing enzymes.

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Figure 1: X-ray crystal structure of 1.
Figure 2: Ultraviolet–visible spectra and XAS data of 1, 2 and 3.
Figure 3: Iron–oxygen intermediates.
Figure 4: Reactivity studies of 2 with aldehydes.

Accession codes

Data deposits

The crystallographic data for 1 have been deposited with the Cambridge Crystallographic Data Center under accession number CCDC 804038.

References

  1. 1

    Solomon, E. I. et al. Geometric and electronic structure/function correlations in non-heme iron enzymes. Chem. Rev. 100, 235–350 (2000)

    CAS  Article  Google Scholar 

  2. 2

    Kovaleva, E. G. & Lipscomb, J. D. Versatility of biological non-heme Fe(II) centers in oxygen activation reactions. Nature Chem. Biol. 4, 186–193 (2008)

    CAS  Article  Google Scholar 

  3. 3

    Blasiak, L. C., Vaillancourt, F. H., Walsh, C. T. & Drennan, C. L. Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis. Nature 440, 368–371 (2006)

    CAS  Article  ADS  Google Scholar 

  4. 4

    Rittle, J. & Green, M. T. Cytochrome P450 compound I: capture, characterization, and C-H bond activation kinetics. Science 330, 933–937 (2010)

    CAS  Article  ADS  Google Scholar 

  5. 5

    Kovaleva, E. G. & Lipscomb, J. D. Crystal structures of Fe2+ dioxygenase superoxo, alkylperoxo, and bound product intermediates. Science 316, 453–457 (2007)

    CAS  Article  ADS  Google Scholar 

  6. 6

    Karlsson, A. et al. Crystal structure of naphthalene dioxygenase: side-on binding of dioxygen to iron. Science 299, 1039–1042 (2003)

    CAS  Article  ADS  Google Scholar 

  7. 7

    Cicchillo, R. M. et al. An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis. Nature 459, 871–874 (2009)

    CAS  Article  ADS  Google Scholar 

  8. 8

    Seo, M. S. et al. [Mn(tmc)(O2)]+: a side-on peroxido manganese(III) complex bearing a non-heme ligand. Angew. Chem. Int. Edn 46, 377–380 (2007)

    CAS  Article  Google Scholar 

  9. 9

    Cho, J. et al. Synthesis, structural, and spectroscopic characterization and reactivities of mononuclear cobalt(III)-peroxo complexes. J. Am. Chem. Soc. 132, 16977–16986 (2010)

    CAS  Article  Google Scholar 

  10. 10

    Cho, J. et al. Geometric and electronic structure and reactivity of a mononuclear ‘side-on’ nickel(III)-peroxo complex. Nature Chem. 1, 568–572 (2009)

    CAS  Article  ADS  Google Scholar 

  11. 11

    Rohde, J.-U. et al. Crystallographic and spectroscopic characterization of a nonheme Fe(IV) = O complex. Science 299, 1037–1039 (2003)

    CAS  Article  ADS  Google Scholar 

  12. 12

    Annaraj, J., Suh, Y., Seo, M. S., Kim, S. O. & Nam, W. Mononuclear nonheme ferric-peroxo complex in aldehyde deformylation. Chem. Commun. 4529–4531 (2005)

  13. 13

    Cramer, C. J., Tolman, W. B., Theopold, K. H. & Rheingold, A. L. Variable character of O-O and M-O bonding in side-on (η2) 1:1 metal complexes of O2 . Proc. Natl Acad. Sci. USA 100, 3635–3640 (2003)

    CAS  Article  ADS  Google Scholar 

  14. 14

    Neese, F. & Solomon, E. I. Detailed spectroscopic and theoretical studies on [Fe(EDTA)(O2)]3–: electronic structure of the side-on ferric-peroxide bond and its relevance to reactivity. J. Am. Chem. Soc. 120, 12829–12848 (1998)

    CAS  Article  Google Scholar 

  15. 15

    Liu, J.-G. et al. Spectroscopic characterization of a hydroperoxo-heme intermediate: conversion of a side-on peroxo to an end-on hydroperoxo complex. Angew. Chem. Int. Edn 48, 9262–9267 (2009)

    CAS  Article  Google Scholar 

  16. 16

    Fukuzumi, S. et al. Crystal structure of a metal ion-bound oxoiron(IV) complex and implications for biological electron transfer. Nature Chem. 2, 756–759 (2010)

    CAS  Article  ADS  Google Scholar 

  17. 17

    Jensen, K. B., McKenzie, C. J., Nielsen, L. P., Pedersen, J. Z. & Svendsen, H. M. Deprotonation of low-spin mononuclear iron(III)-hydroperoxide complexes give transient blue species assigned to high-spin iron(III)-peroxide complexes. Chem. Commun. 1313–1314 (1999)

  18. 18

    Simaan, A. J., Banse, F., Girerd, J.-J., Wieghardt, K. & Bill, E. The electronic structure of non-heme iron(III)-hydroperoxo and iron(III)-peroxo model complexes studied by Mössbauer and electron paramagnetic resonance spectroscopies. Inorg. Chem. 40, 6538–6540 (2001)

    CAS  Article  Google Scholar 

  19. 19

    Wada, A. et al. Reactivity of hydroperoxide bound to a mononuclear non-heme iron site. Inorg. Chem. 41, 616–618 (2002)

    CAS  Article  Google Scholar 

  20. 20

    Westre, T. E. et al. A multiplet analysis of Fe K-edge 1s → 3d pre-edge features of iron complexes. J. Am. Chem. Soc. 119, 6297–6314 (1997)

    CAS  Article  Google Scholar 

  21. 21

    Lehnert, N., Neese, F., Ho, R. Y. N., Que, L., Jr & Solomon, E. I. Electronic structure and reactivity of low-spin Fe(III)−hydroperoxo complexes: comparison to activated bleomycin. J. Am. Chem. Soc. 124, 10810–10822 (2002)

    CAS  Article  Google Scholar 

  22. 22

    Li, F. et al. Characterization of a high-spin non-heme FeIII-OOH intermediate and its quantitative conversion to an FeIV = O complex. J. Am. Chem. Soc. 133, 7256–7259 (2011)

    CAS  Article  Google Scholar 

  23. 23

    Shan, X. et al. X-ray absorption spectroscopic studies of high-spin nonheme (alkylperoxo)iron(III) intermediates. Inorg. Chem. 46, 8410–8417 (2007)

    CAS  Article  Google Scholar 

  24. 24

    Wertz, D. L. & Valentine, J. S. Nucleophilicity of iron-peroxo porphyrin complexes. Struct. Bonding 97, 37–60 (2000)

    CAS  Article  Google Scholar 

  25. 25

    Selke, M. & Valentine, J. S. Switching on the nucleophilic reactivity of a ferric porphyrin peroxo complex. J. Am. Chem. Soc. 120, 2652–2653 (1998)

    CAS  Article  Google Scholar 

  26. 26

    Mayer, J. M. Understanding hydrogen atom transfer: from bond strengths to Marcus theory. Acc. Chem. Res. 44, 36–46 (2011)

    CAS  Article  Google Scholar 

  27. 27

    Sastri, C. V. et al. Axial ligand tuning of a nonheme iron(IV)-oxo unit for hydrogen atom abstraction. Proc. Natl Acad. Sci. USA 104, 19181–19186 (2007)

    CAS  Article  ADS  Google Scholar 

  28. 28

    Vaz, A. D. N., Roberts, E. S. & Coon, M. J. Olefin formation in the oxidative deformylation of aldehydes by cytochrome P-450. Mechanistic implications for catalysis by oxygen-derived peroxide. J. Am. Chem. Soc. 113, 5886–5887 (1991)

    CAS  Article  Google Scholar 

  29. 29

    Akhtar, M., Corina, D., Miller, S., Shyadehi, A. Z. & Wright, J. N. Mechanism of the acyl-carbon cleavage and related reactions catalyzed by multifunctional P-450s: studies on cytochrome P-45017α . Biochemistry 33, 4410–4418 (1994)

    CAS  Article  Google Scholar 

  30. 30

    Solomon, E. I., Wong, S. D., Liu, L. V., Decker, A. & Chow, M. S. Peroxo and oxo intermediates in mononuclear nonheme iron enzymes and related active sites. Curr. Opin. Chem. Biol. 13, 99–113 (2009)

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The work was supported by NRF/MEST of Korea through the CRI (W.N.), the GRL (2010-00353; W.N.), the WCU (R31-2008-000-10010-0; W.N. and J.S.V.) and the 2011 KRICT OASIS Project (W.N.), by NIH grants GM 40392 (E.I.S.) and RR-001209 (K.O.H.), and by NSF grant MCB 0919027 (E.I.S.). J.J.B. acknowledges a Fellowship from NSF EAPSI (OISE-1014685) and the Warner Linfield Award from the University of Michigan. SSRL operations are funded by the Department of Energy (DOE) Office of Science and operated by Stanford University. The SSRL Structural Molecular Biology programme is supported by the DOE, Office of Biological and Environmental Research, and by the NIH, National Center for Research Resources (grant 5P41RR001209), Biomedical Technology Program.

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J.C., J.S.V., E.I.S. and W.N. conceived and designed the experiments. J.C., S.J., S.A.W., L.V.L., E.A.K., J.J.B., M.H.L., B.H. and K.O.H. performed the experiments and analysed the data. J.C., S.A.W., L.V.L., J.S.V., E.I.S. and W.N. co-wrote the Letter.

Corresponding authors

Correspondence to Joan Selverstone Valentine, Edward I. Solomon or Wonwoo Nam.

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The authors declare no competing financial interests.

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This file contains a Supplementary Experimental Section, Supplementary Results and Discussion, Supplementary Acknowledgements, Supplementary References, Supplementary Tables 1-8 and Supplementary Figures 1-23 with legends (see Contents for full details). (PDF 2931 kb)

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Cho, J., Jeon, S., Wilson, S. et al. Structure and reactivity of a mononuclear non-haem iron(III)–peroxo complex. Nature 478, 502–505 (2011). https://doi.org/10.1038/nature10535

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