Identification and Spectroscopic Characterization of Nonheme Iron(III) Hypochlorite Intermediates**

FeIII–hypohalite complexes have been implicated in a wide range of important enzyme-catalyzed halogenation reactions including the biosynthesis of natural products and antibiotics and post-translational modification of proteins. The absence of spectroscopic data on such species precludes their identification. Herein, we report the generation and spectroscopic characterization of nonheme FeIII–hypohalite intermediates of possible relevance to iron halogenases. We show that FeIII-OCl polypyridylamine complexes can be sufficiently stable at room temperature to be characterized by UV/Vis absorption, resonance Raman and EPR spectroscopies, and cryo-ESIMS. DFT methods rationalize the pathways to the formation of the FeIII-OCl, and ultimately FeIV=O, species and provide indirect evidence for a short-lived FeII-OCl intermediate. The species observed and the pathways involved offer insight into and, importantly, a spectroscopic database for the investigation of iron halogenases.

[1]  O. Planas,et al.  Structural modeling of iron halogenases: synthesis and reactivity of halide-iron(IV)-oxo compounds. , 2014, Chemical communications.

[2]  Bin Wang,et al.  Highly reactive nonheme iron(III) iodosylarene complexes in alkane hydroxylation and sulfoxidation reactions. , 2014, Angewandte Chemie.

[3]  S. D. de Visser,et al.  Comparison of the reactivity of nonheme iron(IV)-oxo versus iron(IV)-imido complexes: which is the better oxidant? , 2013, Angewandte Chemie.

[4]  S. D. de Visser,et al.  Mechanistic insight into halide oxidation by non-heme iron complexes. Haloperoxidase versus halogenase activity. , 2013, Chemical communications.

[5]  M. J. Collins,et al.  Nonheme Oxoiron(IV) Complexes of Pentadentate N5 Ligands: Spectroscopy, Electrochemistry, and Oxidative Reactivity. , 2013, Chemical science.

[6]  H. Fujii,et al.  Synthesis, characterization, and reactivity of hypochloritoiron(III) porphyrin complexes. , 2012, Journal of the American Chemical Society.

[7]  G. Roelfes,et al.  Photo-induced oxidation of [Fe(II)(N4Py)CH3CN] and related complexes. , 2012, Dalton transactions.

[8]  A. Lennartson,et al.  An iron(III) iodosylbenzene complex: a masked non-heme Fe(V)O. , 2012, Angewandte Chemie.

[9]  G. Roelfes,et al.  Ligand exchange and spin state equilibria of Fe(II)(N4Py) and related complexes in aqueous media. , 2012, Inorganic chemistry.

[10]  B. Floris,et al.  Mechanistic aspects of vanadium catalysed oxidations with peroxides , 2011 .

[11]  S. D. de Visser,et al.  Nonheme ferric hydroperoxo intermediates are efficient oxidants of bromide oxidation. , 2011, Chemical communications.

[12]  S. P. Visser,et al.  Iron-containing enzymes : versatile catalysts of hydroxylation reactions in nature , 2011 .

[13]  S. D. de Visser,et al.  Steric factors override thermodynamic driving force in regioselectivity of proline hydroxylation by prolyl-4-hydroxylase enzymes. , 2010, The journal of physical chemistry. A.

[14]  J. Ziller,et al.  Formation, structure, and EPR detection of a high spin Fe(IV)-oxo species derived from either an Fe(III)-oxo or Fe(III)-OH complex. , 2010, Journal of the American Chemical Society.

[15]  P. Comba,et al.  Iron-catalyzed halogenation of alkanes: modeling of nonheme halogenases by experiment and DFT calculations. , 2010, Chemistry.

[16]  Alison Butler,et al.  Mechanistic considerations of halogenating enzymes , 2009, Nature.

[17]  S. D. de Visser,et al.  Activation of hydrocarbon C-H bonds by iodosylbenzene: how does it compare with iron(IV)-oxo oxidants? , 2009, Chemical communications.

[18]  S. Fukuzumi,et al.  Water as an oxygen source in the generation of mononuclear nonheme iron(IV) oxo complexes. , 2009, Angewandte Chemie.

[19]  G. van Koten,et al.  Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies. , 2008, Chemical Society reviews.

[20]  C. Walsh,et al.  Halogenation strategies in natural product biosynthesis. , 2008, Chemistry & biology.

[21]  W. Nam,et al.  High-valent iron(IV)-oxo complexes of heme and non-heme ligands in oxygenation reactions. , 2007, Accounts of chemical research.

[22]  C. Walsh,et al.  Two interconverting Fe(IV) intermediates in aliphatic chlorination by the halogenase CytC3. , 2007, Nature chemical biology.

[23]  S. Chapman,et al.  Molecular mechanisms of enzyme-catalysed halogenation. , 2006, Molecular bioSystems.

[24]  C. Walsh,et al.  Nature's inventory of halogenation catalysts: oxidative strategies predominate. , 2006, Chemical reviews.

[25]  M. Hofrichter,et al.  Heme-thiolate haloperoxidases: versatile biocatalysts with biotechnological and environmental significance , 2006, Applied Microbiology and Biotechnology.

[26]  J. Naismith,et al.  Biological halogenation has moved far beyond haloperoxidases. , 2006, Advances in applied microbiology.

[27]  M. Martinho,et al.  New example of a non-heme mononuclear iron(IV) oxo complex. Spectroscopic data and oxidation activity. , 2005, Inorganic chemistry.

[28]  W. Nam,et al.  A Thiolate-Ligated Nonheme Oxoiron(IV) Complex Relevant to Cytochrome P450 , 2005, Science.

[29]  S. V. Kryatov,et al.  Kinetics and mechanisms of formation and reactivity of non-heme iron oxygen intermediates. , 2005, Chemical reviews.

[30]  L. Que,et al.  Dioxygen activation at mononuclear nonheme iron active sites: enzymes, models, and intermediates. , 2004, Chemical reviews.

[31]  D. Mansuy,et al.  Spectroscopic Characterization of an FeIV Intermediate Generated by Reaction of XO− (X = Cl, Br) with an FeII Complex Bearing a Pentadentate Non-Porphyrinic Ligand − Hydroxylation and Epoxidation Activity , 2004 .

[32]  Mi Hee Lim,et al.  Crystallographic and spectroscopic characterization of a nonheme Fe(IV)-O complex. , 2003, Science.

[33]  G. Roelfes,et al.  Resonance Raman evidence for the interconversion between an [FeIII–η1-OOH] 2+ and [FeIII–η2-O2]+ species and mechanistic implications thereof , 1999 .

[34]  Gordon W. Gribble,et al.  Naturally Occurring Organohalogen Compounds , 1998 .

[35]  H. Wagenknecht,et al.  Identification of intermediates in the catalytic cycle of chloroperoxidase. , 1997, Chemistry & biology.

[36]  J. Dawson,et al.  Heme-Containing Oxygenases. , 1996, Chemical reviews.

[37]  L. Que,et al.  Alkane functionalization at nonheme iron centers. Stoichiometric transfer of metal-bound ligands to alkane , 1993 .