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Review
. 2007 Jul;40(7):484-92.
doi: 10.1021/ar700066p. Epub 2007 Jun 2.

Non-heme Fe(IV)-oxo intermediates

Carsten Krebs  1 , Danica Galonić Fujimori, Christopher T Walsh, J Martin Bollinger Jr
Affiliations
Review

Non-heme Fe(IV)-oxo intermediates

Carsten Krebs et al. Acc Chem Res. 2007 Jul.

Abstract

High-valent non-heme iron-oxo intermediates have been proposed for decades as the key intermediates in numerous biological oxidation reactions. In the past three years, the first direct characterization of such intermediates has been provided by studies of several alphaKG-dependent oxygenases that catalyze either hydroxylation or halogenation of their substrates. In each case, the Fe(IV)-oxo intermediate is implicated in cleavage of the aliphatic C-H bond to initiate hydroxylation or halogenation. The observation of non-heme Fe(IV)-oxo intermediates and Fe(II)-containing product(s) complexes with almost identical spectroscopic parameters in the reactions of two distantly related alphaKG-dependent hydroxylases suggests that members of this subfamily follow a conserved mechanism for substrate hydroxylation. In contrast, for the alphaKG-dependent non-heme iron halogenase, CytC3, two distinct Fe(IV) complexes form and decay together, suggesting that they are in rapid equilibrium. The existence of two distinct conformers of the Fe site may be the key factor accounting for the divergence of the halogenase reaction from the more usual hydroxylation pathway after C-H bond cleavage. Distinct transformations catalyzed by other mononuclear non-heme enzymes are likely also to involve initial C-H bond cleavage by Fe(IV)-oxo complexes, followed by diverging reactivities of the resulting Fe(III)-hydroxo/substrate radical intermediates.

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Figures

Figure 1
Figure 1
Comparison of the spectroscopic features of the Fe(IV)-oxo intermediates from TauD (top), P4H (middle), and CytC3 (bottom) A: Comparison of the kinetics of the Fe(IV)-oxo intermediates monitored by SF-absorption spectroscopy using unlabeled (red) and selectively deuterated substrates (blue). B: 4.2-K/53-mT (left) and 4.2-K/8-T (right) Mössbauer spectra of the Fe(IV)-oxo intermediates.
Scheme 1
Scheme 1
Reactions proposed to be mediated by high-valent Fe-oxo intermediates
Scheme 2
Scheme 2
General mechanism of αKG-dependent dioxygenases
Scheme 3
Scheme 3
Reactions catalyzed by the αKG-dependent hydroxylase TH
Scheme 4
Scheme 4
Hydroxylation vs halogenation rebound reactions
Scheme 5
Scheme 5
Reaction catalyzed by the halogenase CytC3
Scheme 6
Scheme 6
Proposed mechanism of IPNS
Scheme 7
Scheme 7
Alternative reactions of the proposed Fe(IV)-oxo intermediate in IPNS
Scheme 8
Scheme 8
Reaction catalyzed by CAS
Scheme 9
Scheme 9
Reaction catalyzed by DAOCS
Scheme 10
Scheme 10
Reaction catalyzed by CarC
See this image and copyright information in PMC

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