Iron Oxo Research Articles

Mononuclear Nonheme High‐Spin (S=2) versus Intermediate‐Spin (S=1) Iron(IV)–Oxo Complexes in Oxidation Reactions

AbstractMononuclear nonheme high‐spin (S=2) iron(IV)–oxo species have been identified as the key intermediates responsible for the C−H bond activation of organic substrates in nonheme iron enzymatic reactions. Herein we report that the C−H bond activation of hydrocarbons by a synthetic mononuclear nonheme high‐spin (S=2) iron(IV)–oxo complex occurs through an oxygen non‐rebound mechanism, as previously demonstrated in the C−H bond activation by nonheme intermediate (S=1) iron(IV)–oxo complexes. We also report that C−H bond activation is preferred over C=C epoxidation in the oxidation of cyclohexene by the nonheme high‐spin (HS) and intermediate‐spin (IS) iron(IV)–oxo complexes, whereas the C=C double bond epoxidation becomes a preferred pathway in the oxidation of deuterated cyclohexene by the nonheme HS and IS iron(IV)–oxo complexes. In the epoxidation of styrene derivatives, the HS and IS iron(IV) oxo complexes are found to have similar electrophilic characters.

Inside Cover: Spectroscopic Characterization and Reactivity of Triplet and Quintet Iron(IV) Oxo Complexes in the Gas Phase (Angew. Chem. Int. Ed. 11/2016)

Inside Cover: Spectroscopic Characterization and Reactivity of Triplet and Quintet Iron(IV) Oxo Complexes in the Gas Phase (Angew. Chem. Int. Ed. 11/2016)

Spectroscopic Characterization and Reactivity of Triplet and Quintet Iron(IV) Oxo Complexes in the Gas Phase.

Closely structurally related triplet and quintet iron(IV) oxo complexes with a tetradentate aminopyridine ligand were generated in the gas phase, spectroscopically characterized, and their reactivities in hydrogen‐transfer and oxygen‐transfer reactions were compared. The spin states were unambiguously assigned based on helium tagging infrared photodissociation (IRPD) spectra of the mass‐selected iron complexes. It is shown that the stretching vibrations of the nitrate counterion can be used as a spectral marker of the central iron spin state.

Spectroscopic Characterization and Reactivity of Triplet and Quintet Iron(IV) Oxo Complexes in the Gas Phase

AbstractClosely structurally related triplet and quintet iron(IV) oxo complexes with a tetradentate aminopyridine ligand were generated in the gas phase, spectroscopically characterized, and their reactivities in hydrogen‐transfer and oxygen‐transfer reactions were compared. The spin states were unambiguously assigned based on helium tagging infrared photodissociation (IRPD) spectra of the mass‐selected iron complexes. It is shown that the stretching vibrations of the nitrate counterion can be used as a spectral marker of the central iron spin state.

Review on High Valent FeVI (Ferrate): A Sustainable Green Oxidant in Organic Chemistry and Transformation of Pharmaceuticals

Iron is the most common metal by mass on earth and represents the basic element of industrial society. The usage of iron to synthesize consumer products and to remediate environment is an attractive approach. This perspective presents applications of the high-valent iron oxo compound FeVIO42– (ferrate) in sustainable organic synthesis and treatment technology. In synthesizing organic molecules, C–H bond activation and selectivity are two basic ingredients of efficiency, which are attainable by ferrate. Examples of hydroxylation of hydrocarbons and conversion of alcohols to aldehyde/ketone are presented. In addition, many other organic molecules of amines, aniline, phenolic, and thiol functionalities can be oxidized by ferrate. This oxidation chemistry of ferrate is expedient in transforming pharmaceuticals, micropollutants in bodies of water with implications for human and ecological health. A wide range of micropollutants, which are commonly found in drinking water resources and wastewater effluents, can...

Computations Reveal a Rich Mechanistic Variation of Demethylation of N-Methylated DNA/RNA Nucleotides by FTO

The fat-mass and obesity-associated (FTO) protein employs an iron(IV) oxo species to demethylate N-methylated nucleic acids. Herein, we use atomistic-theoretical calculations to study the demethylation of the N-methylated DNA/RNA bases 6-methylated adenine (m6A), 3-methylated thymine (m3T), and 3-methylated uracil (m3U). The mechanisms involve in-enzyme hydroxylation of the methyl group, followed by hydrolysis of the oxidized intermediates in aqueous solution to demethylate the bases. The in-enzyme reactions have been studied using quantum mechanical/molecular mechanical (QM/MM) calculations, while the hydrolytic reactions occurring outside the enzyme have been explored with hybrid cluster-continuum (HCC) calculations. When the results obtained with these different methods are combined, the calculated barrier for the overall transformation is consistent with the experimental free energy barrier for the major route of m6A demethylation: in this pathway, adenine’s N1 site acts as an internal base catalyst i...

Iron(IV) or iron(V)? Heterolytic or free radical? Oxidation pathways of a TAML activator in acetonitrile at −40 °C

The oxidation of TAML complex (1) by various oxidants is explored in MeCN with 0.2% water at −40 °C, where the iron(V)oxo complex is stable enough for reliable spectral identification. The iron(V)oxo state is achieved using NaClO even faster than in the case of previously explored m-chloroperoxybenzoic acid. In contrast, H2O2 and organic peroxides (benzoyl peroxide, tert-butylperoxide, and tert-butylhydroperoxide) all convert 1 into the corresponding diiron(IV)-μ-oxo dimer (2) under the same conditions. The latter does not form when (NH4)2[Ce(NO3)6] is employed and the FeIV product obtained does not seem to contain an oxo moiety. In contrast to all other oxidants, the conversion of 1 by tBuOOH into 2 is characterized by non-conventional kinetics, and therefore this reaction was explored in some detail. The evidence is presented that this light-, O2-, TEMPO-, and base-dependent reaction is a free radical process under the conditions used.

Role of the Heme Axial Ligand on the Reactivity of High-Valent Oxo-Iron Porphyrin Intermediate

High-valent iron oxo species have been known as the key reaction intermediates in the catalytic cycles of oxygen activating iron enzymes. In heme enzymes, oxoiron(IV) porphyrin π-cation radical species named compound I were characterized in the catalytic cycles of peroxidases, catalases, and cytochrome P450. These heme enzymes have the same heme (iron protoporphyrin IX), but different heme proximal (axial) ligands; histidine in peroxidase, tyrosine in catalase, and cysteine in cytochrome P450, which are highly conserved in these heme enzymes. Therefore, the axial ligand has been believed to tune the reactivity of compound I. To reveal functional role of the axial ligand, the axial ligand effect on the reactivity of high-valent iron oxo species has been studied systematically with synthetic enzyme model complexes. In this presentation, we present how the heme axial ligand modulate the reactivity of compound I. Compound I model complexes, (TMP+ ·)FeIVO(L), changed its reactivity by identity of the axial ligand, but the reactivity did not correlate with any spectroscopic data of (TMP+ ·)FeIVO(L), such as the redox potential and Fe=O bond strength. Surprisingly, a clear correlation was found between the reactivity of (TMP+ ·)FeIVO(L) and FeII/FeIII redox potential of (TMP)FeIIIL, the final reaction product. Axail ligand-exchange experiments and theoretical calculations showed linear free-energy relationship, in which the axial ligand modulates the reaction free energy by changing the stability of (TMP)FeIII(L) more significantly than (TMP+ ·)FeIVO(L). All results indicate that the reactivity of compound I is controlled by thermodynamic stability of the ground state of the final reaction product, not but compound I itself. Therefore, the heme axial ligand activates compound I by stabilizing the resting state, not by activating compound I. The proposed mechanism can be explained by the trans-ligand effect of the oxo-ligand, which migrates from compound I to substrate in the reaction.

Decarboxylation of fatty acids to terminal alkenes by cytochrome P450 compound I.

OleT(JE), a cytochrome P450, catalyzes the conversion of fatty acids to terminal alkenes using hydrogen peroxide as a cosubstrate. Analytical studies with an eicosanoic acid substrate show that the enzyme predominantly generates nonadecene and that carbon dioxide is the one carbon coproduct of the reaction. The addition of hydrogen peroxide to a deuterated substrate-enzyme (E-S) complex results in the transient formation of an iron(IV) oxo π cation radical (Compound I) intermediate which is spectroscopically indistinguishable from those that perform oxygen insertion chemistries. A kinetic isotope effect for Compound I decay suggests that it abstracts a substrate hydrogen atom to initiate fatty acid decarboxylation. Together, these results indicate that the initial mechanism for alkene formation, which does not result from oxygen rebound, is similar to that widely suggested for P450 monooxygenation reactions.

In Silico Screening of Iron-Oxo Catalysts for CH Bond Cleavage

Inspired by oxidation enzymes such as P450 and TauD, several groups have based their research on the iron–oxo moiety in the field of alkanes partial oxidation. Still, the controlled cleavage and oxidation of the aliphatic C–H bond remains a prized goal in chemistry. We present here a computational methodology to predict the comparative reactivity of iron–oxo complexes for this process from linear relations based on the sole electronic structure of the reactant state. The efficient correlation of the C–H activation barrier to a simple but intuitive molecular orbital descriptor enables the design of ligands that permit low barrier C–H abstraction steps and the fast screening of novel potential complexes. The activation of the catalyst by a multidentate effect is also evidenced. We anticipate this study to improve the rational design of hydrocarbon oxidation catalysts.

Synthesis of Ethers from Carbonyl Compounds by Reductive Etherification Catalyzed by Iron(III) and Silyl Chloride

A simple iron- and silyl chloride catalyzed method for the preparation of symmetrical and nonsymmetrical ethers is presented. Various aldehydes and ketones were reductively etherified by using triethylsilane as a reducing agent in the presence of 2 mol% of iron(III) oxo acetate and 8 mol% of chloro(trimethyl)silane. The reactions can be carried out at ambient temperatures and pressures with ethyl acetate as the solvent.

Structures, bonding and reactivity of iron and manganese high-valent metal-oxo complexes: A computational investigation

Iron and manganese ions with terminal oxo and hydroxo ligands are discovered as key intermediates in several synthetic and biochemical catalytic cycles. Since many of these species possess vigorous catalytic abilities, they are extremely transient in nature and experiments which probe the structure and bonding on such elusive species are still rare. We present here comprehensive computational studies on eight iron and manganese oxo and hydroxo (FeIII/IV/V-O, FeIII-OH and MnIII/IV/V-O, MnIII-OH) species using dispersion corrected (B3LYP-D2) density functional method. By computing all the possible spin states for these eight species, we set out to determine the ground state S value of these species; and later on employing MO analysis, we have analysed the bonding aspects which contribute to the high reactivity of these species. Direct structural comparison to iron and manganese-oxo species are made and the observed similarity and differences among them are attributed to the intricate metal–oxygen bonding. By thoroughly probing the bonding in all these species, their reactivity towards common chemical reactions such as C–H activation and oxygen atom transfer are discussed. In this work, we present comprehensive computational studies on iron and manganese high-valent oxo and hydroxo species using dispersion corrected (B3LYP-D2) density functional method. By thoroughly probing the bonding in all these species, their reactivity towards common chemical reactions such as C-H activation and oxygen atom transfer are commented.

Evidence for an oxygen evolving iron-oxo-cerium intermediate in iron-catalysed water oxidation.

The non-haem iron complex α-[Fe(II)(CF3SO3)2(mcp)] (mcp=(N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)-1,2-cis-diaminocyclohexane) reacts with Ce(IV) to oxidize water to O2, representing an iron-based functional model for the oxygen evolving complex of photosystem II. Here we trap an intermediate, characterized by cryospray ionization high resolution mass spectrometry and resonance Raman spectroscopy, and formulated as [(mcp)Fe(IV)(O)(μ-O)Ce(IV)(NO3)3](+), the first example of a well-characterized inner-sphere complex to be formed in cerium(IV)-mediated water oxidation. The identification of this reactive Fe(IV)-O-Ce(IV) adduct may open new pathways to validate mechanistic notions of an analogous Mn(V)-O-Ca(II) unit in the oxygen evolving complex that is responsible for carrying out the key O-O bond forming step.

Studying the Structural and Electronic Configurations during Photocatalytic Activation of O2 at a Diiron(II) Complex

Several mono and carboxylate-bridged diiron nuclear enzymes are critical in activating dioxygen in biological processes such as DNA synthesis, hydrocarbon metabolism and cell proliferation1. Iron-containing enzymes such as cytochrome P450, peroxidases, catalases and methane monooxygenase (MMO) have been shown to activate dioxygen by using two electrons and protons to produce iron (IV) oxo intermediates2. The remarkable efficiency of these enzymes is attributed to formation of iron(IV) cations which serve as active oxidants in enzymatic reactions and can attack C-H bonds of a wide range of hydrocarbon substrates. It is widely postulated that ferryl-oxo species are key intermediates in the mechanism of cytochrome P450 and MMO. However due to the complexity of protein environments in biological iron enzymatic systems, monitoring the structural changes occurring during dioxygen activation is a complex undertaking.This project serves to study the light driven activation of a well characterized artificial analogue of an diiron MMO enzyme, (µ-peroxo) (µ-carboxylato) diiron(III) complex, [Fe2(µ-O2)(N-EtHPTB)(µ-PhCO2)]2+ in a chromophore/diiron complex assembled unit. Such types of assemblies provide new avenues for study of catalytic reaction mechanisms. They are promising examples of artificial molecular systems leading to dioxygen activation as visible light is efficiently absorbed at the chromophore, and light energy is in turn converted into a chemical potential via an electron relay through charge accumulation processes at the iron metal center. Formation of high valent iron peroxo species have been shown by UV-Vis, EPR and Resonance Raman spectroscopy as well as X-ray spectroscopic analysis. XANES and EXAFS revealed formation of an iron peroxo and oxo species with shorter bond distances and different coordination numbers.(1) Do, L. H.; Hayashi, T.; Moenne-Loccoz, P.; Lippard, S. J. J.Am.Chem.Soc. 2010, 132, 1273.(2) Lawrence Que, J.; Y.N.Ho, R. Chem.Rev 1996, 96, 2607.

Oxidation of methane by an N-bridged high-valent diiron-oxo species: electronic structure implications on the reactivity.

High-valent iron-oxo species are key intermediates in C-H bond activation of several substrates including alkanes. The biomimic heme and non-heme mononuclear Fe(IV)=O complexes are very popular in this area and have been thoroughly studied over the years. These species despite possessing aggressive catalytic ability, cannot easily activate inert C-H bonds such as those of methane. In this context dinuclear complexes have gained attention, particularly μ-nitrido dinuclear iron species [(TPP)(m-CBA)Fe(IV)(μ-N)Fe(IV)(O)(TPP(˙+))](-) reported lately exhibits remarkable catalytic abilities towards substrates such as methane. Here using DFT methods, we have explored the electronic structure and complex spin-state energetics present in this species. To gain insights into the nature of bonding, we have computed the absorption, the EPR and the Mössbauer parameters and have probed the mechanism of methane oxidation by the dinuclear Fe(IV)=O species. Calculated results are in agreement with the experimental data and our calculations predict that in [(TPP)(m-CBA)Fe(IV)(μ-N)Fe(IV)(O)(TPP(˙+))](-)species, the two high-spin iron centres are antiferromagnetically coupled leading to a doublet ground state. Our calculations estimate an extremely low kinetic barrier of 26.6 kJ mol(-1) (at doublet surface) for the C-H bond activation of methane by the dinuclear Fe(IV)=O species. Besides these mechanistic studies on the methane activation reveal the unique electronic cooperativity present in this type of dinuclear complex and unravel the key question of why mononuclear analogues are unable to perform such reactions.

Heme enzymes. Neutron cryo-crystallography captures the protonation state of ferryl heme in a peroxidase.

Heme enzymes activate oxygen through formation of transient iron-oxo (ferryl) intermediates of the heme iron. A long-standing question has been the nature of the iron-oxygen bond and, in particular, the protonation state. We present neutron structures of the ferric derivative of cytochrome c peroxidase and its ferryl intermediate; these allow direct visualization of protonation states. We demonstrate that the ferryl heme is an Fe(IV)=O species and is not protonated. Comparison of the structures shows that the distal histidine becomes protonated on formation of the ferryl intermediate, which has implications for the understanding of O-O bond cleavage in heme enzymes. The structures highlight the advantages of neutron cryo-crystallography in probing reaction mechanisms and visualizing protonation states in enzyme intermediates.

Demonstration of the Heterolytic OO Bond Cleavage of Putative Nonheme Iron(II)OOH(R) Complexes for Fenton and Enzymatic Reactions

AbstractOne‐electron reduction of mononuclear nonheme iron(III) hydroperoxo (FeIIIOOH) and iron(III) alkylperoxo (FeIIIOOR) complexes by ferrocene (Fc) derivatives resulted in the formation of the corresponding iron(IV) oxo complexes. The conversion rates were dependent on the concentration and oxidation potentials of the electron donors, thus indicating that the reduction of the iron(III) (hydro/alkyl)peroxo complexes to their one‐electron reduced iron(II) (hydro/alkyl)peroxo species is the rate‐determining step, followed by the heterolytic OO bond cleavage of the putative iron(II) (hydro/alkyl)peroxo species to give the iron(IV) oxo complexes. Product analysis supported the heterolytic OO bond‐cleavage mechanism. The present results provide the first example showing the one‐electron reduction of iron(III) (hydro/alkyl)peroxo complexes and the heterolytic OO bond cleavage of iron(II) (hydro/alkyl)peroxo species to form iron(IV) oxo intermediates which occur in nonheme iron enzymatic and Fenton reactions.

Highly reactive nonheme iron(III) iodosylarene complexes in alkane hydroxylation and sulfoxidation reactions.

High-spin iron(III) iodosylarene complexes bearing an N-methylated cyclam ligand are synthesized and characterized using various spectroscopic methods. The nonheme high-spin iron(III) iodosylarene intermediates are highly reactive oxidants capable of activating strong C-H bonds of alkanes; the reactivity of the iron(III) iodosylarene intermediates is much greater than that of the corresponding iron(IV) oxo complex. The electrophilic character of the iron(III) iodosylarene complexes is demonstrated in sulfoxidation reactions.

Highly Reactive Nonheme Iron(III) Iodosylarene Complexes in Alkane Hydroxylation and Sulfoxidation Reactions

AbstractHigh‐spin iron(III) iodosylarene complexes bearing an N‐methylated cyclam ligand are synthesized and characterized using various spectroscopic methods. The nonheme high‐spin iron(III) iodosylarene intermediates are highly reactive oxidants capable of activating strong CH bonds of alkanes; the reactivity of the iron(III) iodosylarene intermediates is much greater than that of the corresponding iron(IV) oxo complex. The electrophilic character of the iron(III) iodosylarene complexes is demonstrated in sulfoxidation reactions.

The Influence of Structural Parameters on the Reactivity of Model Complexes for Compound II: A Mini Review

The present brief review aims at elucidation of the parameters affecting the properties and reactivity of high valent iron(IV) oxo porphyrin complexes, being models of compound II reactive intermediate known from biochemistry of cytochromes and peroxidases. The stress is put on the influence of the axial ligand and porphyrin ring substituents, with special attention on implications for their catalytic activity.