A tale of two topological isomers: Uptuning [FeIV(O)(Me4cyclam)]2+ for olefin epoxidation.

TMC-anti and TMC-syn, the two topological isomers of [FeIV(O)(TMC)(CH3CN)]2+ (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane, or Me4cyclam), differ in the orientations of their FeIV=O units relative to the four methyl groups of the TMC ligand framework. The FeIV=O unit of TMC-anti points away from the four methyl groups, while that of TMC-syn is surrounded by the methyl groups, resulting in differences in their oxidative reactivities. TMC-syn reacts with HAT (hydrogen atom transfer) substrates at 1.3- to 3-fold faster rates than TMC-anti, but the reactivity difference increases dramatically in oxygen-atom transfer reactions. R2S substrates are oxidized into R2S=O products at rates 2-to-3 orders of magnitude faster by TMC-syn than TMC-anti. Even more remarkably, TMC-syn epoxidizes all the olefin substrates in this study, while TMC-anti reacts only with cis-cyclooctene but at a 100-fold slower rate. Comprehensive quantum chemical calculations have uncovered the key factors governing such reactivity differences found between these two topological isomers.

106-fold faster C-H bond hydroxylation by a CoIII,IV2(µ-O)2 complex [via a CoIII2(µ-O)(µ-OH) intermediate] versus its FeIIIFeIV analog.

The hydroxylation of C-H bonds can be carried out by the high-valent CoIII,IV2(µ-O)2 complex 2a supported by the tetradentate tris(2-pyridylmethyl)amine ligand via a CoIII2(µ-O)(µ-OH) intermediate (3a). Complex 3a can be independently generated either by H-atom transfer (HAT) in the reaction of 2a with phenols as the H-atom donor or protonation of its conjugate base, the CoIII2(µ-O)2 complex 1a. Resonance Raman spectra of these three complexes reveal oxygen-isotope-sensitive vibrations at 560 to 590 cm-1 associated with the symmetric Co-O-Co stretching mode of the Co2O2 diamond core. Together with a Co•••Co distance of 2.78(2) Å previously identified for 1a and 2a by Extended X-ray Absorption Fine Structure (EXAFS) analysis, these results provide solid evidence for their "diamond core" structural assignments. The independent generation of 3a allows us to investigate HAT reactions of 2a with phenols in detail, measure the redox potential and pKa of the system, and calculate the O-H bond strength (DO-H) of 3a to shed light on the C-H bond activation reactivity of 2a. Complex 3a is found to be able to transfer its hydroxyl ligand onto the trityl radical to form the hydroxylated product, representing a direct experimental observation of such a reaction by a dinuclear cobalt complex. Surprisingly, reactivity comparisons reveal 2a to be 106-fold more reactive in oxidizing hydrocarbon C-H bonds than corresponding FeIII,IV2(µ-O)2 and MnIII,IV2(µ-O)2 analogs, an unexpected outcome that raises the prospects for using CoIII,IV2(µ-O)2 species to oxidize alkane C-H bonds.

NMR and Mössbauer Studies Reveal a Temperature-Dependent Switch from S = 1 to 2 in a Nonheme Oxoiron(IV) Complex with Faster C-H Bond Cleavage Rates.

S = 2 FeIV═O centers generated in the active sites of nonheme iron oxygenases cleave substrate C-H bonds at rates significantly faster than most known synthetic FeIV═O complexes. Unlike the majority of the latter, which are S = 1 complexes, [FeIV(O)(tris(2-quinolylmethyl)amine)(MeCN)]2+ (3) is a rare example of a synthetic S = 2 FeIV═O complex that cleaves C-H bonds 1000-fold faster than the related [FeIV(O)(tris(pyridyl-2-methyl)amine)(MeCN)]2+ complex (0). To rationalize this significant difference, a systematic comparison of properties has been carried out on 0 and 3 as well as related complexes 1 and 2 with mixed pyridine (Py)/quinoline (Q) ligation. Interestingly, 2 with a 2-Q-1-Py donor combination cleaves C-H bonds at 233 K with rates approaching those of 3, even though Mössbauer analysis reveals 2 to be S = 1 at 4 K. At 233 K however, 2 becomes S = 2, as shown by its 1H NMR spectrum. These results demonstrate a unique temperature-dependent spin-state transition from triplet to quintet in oxoiron(IV) chemistry that gives rise to the high C-H bond cleaving reactivity observed for 2.

Class Ib Ribonucleotide Reductases: Activation of a Peroxido-MnIIMnIII to Generate a Reactive Oxo-MnIIIMnIV Oxidant.

In the postulated catalytic cycle of class Ib Mn2 ribonucleotide reductases (RNRs), a MnII2 core is suggested to react with superoxide (O2·-) to generate peroxido-MnIIMnIII and oxo-MnIIIMnIV entities prior to proton-coupled electron transfer (PCET) oxidation of tyrosine. There is limited experimental support for this mechanism. We demonstrate that [MnII2(BPMP)(OAc)2](ClO4) (1, HBPMP = 2,6-bis[(bis(2 pyridylmethyl)amino)methyl]-4-methylphenol) was converted to peroxido-MnIIMnIII (2) in the presence of superoxide anion that converted to (µ-O)(µ-OH)MnIIIMnIV (3) via the addition of an H+-donor (p-TsOH) or (µ-O)2MnIIIMnIV (4) upon warming to room temperature. The physical properties of 3 and 4 were probed using UV-vis, EPR, X-ray absorption, and IR spectroscopies and mass spectrometry. Compounds 3 and 4 were capable of phenol oxidation to yield a phenoxyl radical via a concerted PCET oxidation, supporting the proposed mechanism of tyrosyl radical cofactor generation in RNRs. The synthetic models demonstrate that the postulated O2/Mn2/tyrosine activation mechanism in class Ib Mn2 RNRs is plausible and provides spectral insights into intermediates currently elusive in the native enzyme.

Formation of a Reactive [Mn(III)-O-Ce(IV)] Species and its Facile Equilibrium with Related Mn(IV)(OX) (X = Sc or H) Complexes.

Lewis acid-bound high valent Mn-oxo species are of great importance due to their relevance to photosystem II. Here, we report the synthesis of a unique [(BnTPEN)Mn(III)-O-Ce(IV)(NO3 )4 ]+ adduct (2) by the reaction of (BnTPEN)Mn(II) (1) with 4 eq. ceric ammonium nitrate. 2 has been characterized using UV/Vis, NMR, resonance Raman spectroscopy, as well as by mass spectrometry. Treatment of 2 with Sc(III)(OTf)3 results in the formation of (BnTPEN)Mn(IV)-O-Sc(III) (3), while HClO4 addition to 2 forms (BnTPEN)Mn(IV)-OH (4), reverting to 2 upon Ce(III)(NO3 )3 addition. 2 can also be prepared by the oxidation of 1 eq. Ce(III)(NO3 )3 with [(BnTPEN)Mn(IV)=O]2+ (5). In addition, the EPR spectroscopy revealed the elegant temperature-dependent equilibria between 2 and Mn(IV) species. The binding of redox-active Ce(IV) boosts electron transfer efficiency of 2 towards ferrocenes. Remarkably, the newly characterized Mn(III)-O-Ce(IV) species can carry out O-atom and H-atom transfer reactions.

Explorations of the nonheme high-valent iron-oxo landscape: crystal structure of a synthetic complex with an [FeIV2(µ-O)2] diamond core relevant to the chemistry of sMMOH.

Methanotrophic bacteria utilize methane monooxygenase (MMO) to carry out the first step in metabolizing methane. The soluble enzymes employ a hydroxylase component (sMMOH) with a nonheme diiron active site that activates O2 and generates a powerful oxidant capable of converting methane to methanol. It is proposed that the diiron(II) center in the reduced enzyme reacts with O2 to generate a diferric-peroxo intermediate called P that then undergoes O-O cleavage to convert into a diiron(IV) derivative called Q, which carries out methane hydroxylation. Most (but not all) of the spectroscopic data of Q accumulated by various groups to date favor the presence of an FeIV2(µ-O)2 unit with a diamond core. The Que lab has had a long-term interest in making synthetic analogs of iron enzyme intermediates. To this end, the first crystal structure of a complex with a FeIIIFeIV(µ-O)2 diamond core was reported in 1999, which exhibited an Fe⋯Fe distance of 2.683(1) Å. Now more than 20 years later, a complex with an FeIV2(µ-O)2 diamond core has been synthesized in sufficient purity to allow diffraction-quality crystals to be grown. Its crystal structure has been solved, revealing an Fe⋯Fe distance of 2.711(4) Å for comparison with structural data for related complexes with lower iron oxidation states.

Nonheme Diiron Oxygenase Mimic That Generates a Diferric-Peroxo Intermediate Capable of Catalytic Olefin Epoxidation and Alkane Hydroxylation Including Cyclohexane.

Herein are described substrate oxidations with H2O2 catalyzed by [FeII(IndH)(CH3CN)3](ClO4)2 [IndH = 1,3-bis(2'-pyridylimino)isoindoline], involving a spectroscopically characterized (µ-oxo)(µ-1,2-peroxo)diiron(III) intermediate (2) that is capable of olefin epoxidation and alkane hydroxylation including cyclohexane. Species 2 also converts ketones to lactones with a decay rate dependent on [ketone], suggesting direct nucleophilic attack of the substrate carbonyl group by the peroxo species. In contrast, peroxo decay is unaffected by the addition of olefins or alkanes, but the label from H218O is incorporated into the the epoxide and alcohol products, implicating a high-valent iron-oxo oxidant that derives from O-O bond cleavage of the peroxo intermediate. These results demonstrate an ambiphilic diferric-peroxo intermediate that mimics the range of oxidative reactivities associated with O2-activating nonheme diiron enzymes.

Spontaneous Formation of an Fe/Mn Diamond Core: Models for the Fe/Mn Sites in Class 1c Ribonucleotide Reductases.

A handful of oxygen-activating enzymes has recently been found to contain Fe/Mn active sites, like Class 1c ribonucleotide reductases and R2-like ligand-binding oxidase, which are closely related to their better characterized diiron cousins. These enzymes are proposed to form high-valent intermediates with Fe-O-Mn cores. Herein, we report the first examples of synthetic Fe/Mn complexes that mimic doubly bridged intermediates proposed for enzymatic oxygen activation. Fe K-edge extended X-ray absorption fine structure (EXAFS) analysis has been used to characterize the structures of each of these compounds. Linear compounds accurately model the Fe···Mn distances found in Fe/Mn proteins in their resting states, and doubly bridged diamond core compounds accurately model the distances found in high-valent biological intermediates. Unlike their diiron analogues, the paramagnetic nature of Fe/Mn compounds can be analyzed by EPR, revealing S = 1/2 signals that reflect antiferromagnetic coupling between the high-spin Fe(III) and Mn(III) units of heterobimetallic centers. These compounds undergo electron transfer with various ferrocenes, linear compounds being capable of oxidizing diacetyl ferrocene, a weak reductant, and diamond core compounds being capable of oxidizing acetyl ferrocene. Diamond core compounds can also perform HAT reactions from substrates with X-H bonds with bond dissociation free energies (BDFEs) up to 75 kcal/mol and are capable of oxidizing TEMPO-H at rates of 0.32-0.37 M-1 s-1, which are comparable to those reported for some mononuclear FeIII-OH and MnIII-OH compounds. However, such reactivity is not observed for the corresponding diiron compounds, a difference that Nature may have taken advantage of in evolving enzymes with heterobimetallic active sites.

Tuning the H-Atom Transfer Reactivity of Iron(IV)-Oxo Complexes as Probed by Infrared Photodissociation Spectroscopy.

Reactivities of non-heme iron(IV)-oxo complexes are mostly controlled by the ligands. Complexes with tetradentate ligands such as [(TPA)FeO]2+ (TPA=tris(2-pyridylmethyl)amine) belong to the most reactive ones. Here, we show a fine-tuning of the reactivity of [(TPA)FeO]2+ by an additional ligand X (X=CH3 CN, CF3 SO3- , ArI, and ArIO; ArI=2-(t BuSO2 )C6 H4 I) attached in solution and reveal a thus far unknown role of the ArIO oxidant. The HAT reactivity of [(TPA)FeO(X)]+/2+ decreases in the order of X: ArIO > MeCN > ArI ≈ TfO- . Hence, ArIO is not just a mere oxidant of the iron(II) complex, but it can also increase the reactivity of the iron(IV)-oxo complex as a labile ligand. The detected HAT reactivities of the [(TPA)FeO(X)]+/2+ complexes correlate with the Fe=O and FeO-H stretching vibrations of the reactants and the respective products as determined by infrared photodissociation spectroscopy. Hence, the most reactive [(TPA)FeO(ArIO)]2+ adduct in the series has the weakest Fe=O bond and forms the strongest FeO-H bond in the HAT reaction.

Unmasking Steps in Intramolecular Aromatic Hydroxylation by a Synthetic Nonheme Oxoiron(IV) Complex.

In this study, a methyl group on the classic tetramethylcyclam (TMC) ligand framework is replaced with a benzylic group to form the metastable [FeIV (Osyn )(Bn3MC)]2+ (2-syn; Bn3MC=1-benzyl-4,8,11-trimethyl-1,4,8,11-tetraazacyclotetradecane) species at -40 °C. The decay of 2-syn with time at 25 °C allows the unprecedented monitoring of the steps involved in the intramolecular hydroxylation of the ligand phenyl ring to form the major FeIII -OAr product 3. At the same time, the FeII (Bn3MC)2+ (1) precursor to 2-syn is re-generated in a 1:2 molar ratio relative to 3, accounting for the first time for all the electrons involved and all the Fe species derived from 2-syn as shown in the following balanced equation: 3 [FeIV (O)(LPh )]2+ (2-syn)→2 [FeIII (LOAr )]2+ (3)+[FeII (LPh )]2+ (1)+H2 O. This system thus serves as a paradigm for aryl hydroxylation by FeIV =O oxidants described thus far. It is also observed that 2-syn can be intercepted by certain hydrocarbon substrates, thereby providing a means to assess the relative energetics of aliphatic and aromatic C-H hydroxylation in this system.

Sc3+-Promoted O-O Bond Cleavage of a (µ-1,2-Peroxo)diiron(III) Species Formed from an Iron(II) Precursor and O2 to Generate a Complex with an FeIV2(µ-O)2 Core.

Soluble methane monooxygenase (sMMO) carries out methane oxidation at 4 °C and under ambient pressure in a catalytic cycle involving the formation of a peroxodiiron(III) intermediate (P) from the oxygenation of the diiron(II) enzyme and its subsequent conversion to Q, the diiron(IV) oxidant that hydroxylates methane. Synthetic diiron(IV) complexes that can serve as models for Q are rare and have not been generated by a reaction sequence analogous to that of sMMO. In this work, we show that [FeII(Me3NTB)(CH3CN)](CF3SO3)2 (Me3NTB = tris((1-methyl-1H-benzo[d]imidazol-2-yl)methyl)amine) (1) reacts with O2 in the presence of base, generating a (µ-1,2-peroxo)diiron(III) adduct with a low O-O stretching frequency of 825 cm-1 and a short Fe···Fe distance of 3.07 Å. Even more interesting is the observation that the peroxodiiron(III) complex undergoes O-O bond cleavage upon treatment with the Lewis acid Sc3+ and transforms into a bis(µ-oxo)diiron(IV) complex, thus providing a synthetic precedent for the analogous conversion of P to Q in the catalytic cycle of sMMO.

Dioxygen Activation by Nonheme Diiron Enzymes: Diverse Dioxygen Adducts, High-Valent Intermediates, and Related Model Complexes.

A growing subset of metalloenzymes activates dioxygen with nonheme diiron active sites to effect substrate oxidations that range from the hydroxylation of methane and the desaturation of fatty acids to the deformylation of fatty aldehydes to produce alkanes and the six-electron oxidation of aminoarenes to nitroarenes in the biosynthesis of antibiotics. A common feature of their reaction mechanisms is the formation of O2 adducts that evolve into more reactive derivatives such as diiron(II,III)-superoxo, diiron(III)-peroxo, diiron(III,IV)-oxo, and diiron(IV)-oxo species, which carry out particular substrate oxidation tasks. In this review, we survey the various enzymes belonging to this unique subset and the mechanisms by which substrate oxidation is carried out. We examine the nature of the reactive intermediates, as revealed by X-ray crystallography and the application of various spectroscopic methods and their associated reactivity. We also discuss the structural and electronic properties of the model complexes that have been found to mimic salient aspects of these enzyme active sites. Much has been learned in the past 25 years, but key questions remain to be answered.

CeIV - and HClO4 -Promoted Assembly of an Fe2IV (µ-O)2 Diamond Core from its Monomeric FeIV =O Precursor at Room Temperature.

Diiron(IV)-oxo species are proposed to effect the cleavage of strong C-H bonds by nonheme diiron enzymes such as soluble methane monooxygenase (sMMO) and fatty acid desaturases. However, synthetic mimics of such diiron(IV) oxidants are rare. Herein we report the reaction of (TPA*)FeII (1) (TPA*=tris(3,5-dimethyl-4-methoxypyridyl-2-methyl)amine) in CH3 CN with 4 equiv CAN and 200 equiv HClO4 at 20 °C to form a complex with an [FeIV2 (µ-O)2 ]4+ core. CAN and HClO4 play essential roles in this unprecedented transformation, in which the comproportionation of FeIII -O-CeIV and FeIV =O/Ce4+ species is proposed to be involved in the assembly of the [FeIV2 (µ-O)2 ]4+ core.

Bio-inspired Nonheme Iron Oxidation Catalysis: Involvement of Oxoiron(V) Oxidants in Cleaving Strong C-H Bonds.

Nonheme iron enzymes generate powerful and versatile oxidants that perform a wide range of oxidation reactions, including the functionalization of inert C-H bonds, which is a major challenge for chemists. The oxidative abilities of these enzymes have inspired bioinorganic chemists to design synthetic models to mimic their ability to perform some of the most difficult oxidation reactions and study the mechanisms of such transformations. Iron-oxygen intermediates like iron(III)-hydroperoxo and high-valent iron-oxo species have been trapped and identified in investigations of these bio-inspired catalytic systems, with the latter proposed to be the active oxidant for most of these systems. In this Review, we highlight the recent spectroscopic and mechanistic advances that have shed light on the various pathways that can be accessed by bio-inspired nonheme iron systems to form the high-valent iron-oxo intermediates.

Acid pKa Dependence in O-O Bond Heterolysis of a Nonheme FeIII-OOH Intermediate To Form a Potent FeV═O Oxidant with Heme Compound I-Like Reactivity.

Protons play essential roles in natural systems in controlling O-O bond cleavage of peroxoiron(III) species to give rise to the high-valent iron oxidants that carry out the desired transformations. Herein, we report kinetic and mechanistic evidence that acids can control the mode of O-O bond cleavage for a nonheme S = 1/2 FeIII-OOH species [(BnTPEN)FeIII(OOH)]2+ (2, BnTPEN = N-benzyl-N,N',N'-tris(2-pyridylmethyl)-1,2-diaminoethane). Addition of acids having pKa values of >8.5 in CH3CN results in O-O bond homolysis, leading to the formation of hydroxyl radicals that give rise to alcohol/ketone (A/K) ratios of around 1 in the oxidation of cyclohexane. However, the introduction of acids with pKa values of <8.5 elicits a different outcome, namely the achievement of A/K ratios of as high as 9, the observation of rapid and catalytic hydroxylation of cyclohexane, and a million-fold acceleration in the decay rate of the FeIII-OOH intermediate at -40 °C. These results implicate the generation of a highly reactive FeV═O species via proton-assisted O-O bond heterolysis of the FeIII-OOH intermediate, which is unprecedented for nonheme iron complexes supported by neutral pentadentate ligands and serves as a nonheme analogue for heme enzyme compounds I.

Spectroscopic and Reactivity Comparisons between Nonheme Oxoiron(IV) and Oxoiron(V) Species Bearing the Same Ancillary Ligand.

This work directly compares the spectroscopic and reactivity properties of an oxoiron(IV) and an oxoiron(V) complex that are supported by the same neutral tetradentate N-based PyNMe3 ligand. A complete spectroscopic characterization of the oxoiron(IV) species (2) reveals that this compound exists as a mixture of two isomers. The reactivity of the thermodynamically more stable oxoiron(IV) isomer (2b) is directly compared to that exhibited by the previously reported 1e--oxidized analogue [FeV(O)(OAc)(PyNMe3)]2+ (3). Our data indicates that 2b is 4 to 5 orders of magnitude slower than 3 in hydrogen atom transfer (HAT) from C-H bonds. The origin of this huge difference lies in the strength of the O-H bond formed after HAT by the oxoiron unit, the O-H bond derived from 3 being about 20 kcal·mol-1 stronger than that from 2b. The estimated bond strength of the FeIVO-H bond of 100 kcal·mol-1 is very close to the reported values for highly active synthetic models of compound I of cytochrome P450. In addition, this comparative study provides direct experimental evidence that the lifetime of the carbon-centered radical that forms after the initial HAT by the high valent oxoiron complex depends on the oxidation state of the nascent Fe-OH complex. Complex 2b generates long-lived carbon-centered radicals that freely diffuse in solution, while 3 generates short-lived caged radicals that rapidly form product C-OH bonds, so only 3 engages in stereoretentive hydroxylation reactions. Thus, the oxidation state of the iron center modulates not only the rate of HAT but also the rate of ligand rebound.

Structural implications of the paramagnetically shifted NMR signals from pyridine H atoms on synthetic nonheme FeIV=O complexes.

Oxoiron(IV) motifs are found in important intermediates in many enzymatic cycles that involve oxidations. Over half of the reported synthetic nonheme oxoiron(IV) analogs incorporate heterocyclic donors, with a majority of them comprising pyridines. Herein, we report 1H-NMR studies of oxoiron(IV) complexes containing pyridines that are arranged in different configurations relative to the Fe = O unit and give rise to paramagnetically shifted resonances that differ by as much as 50 ppm. The strong dependence of 1H-NMR shifts on the different configurations and orientation of pyridines relative to the oxoiron(IV) unit demonstrates how unpaired electronic spin density of the iron center affects the chemical shifts of these protons.

NMR Reveals That a Highly Reactive Nonheme FeIV =O Complex Retains Its Six-Coordinate Geometry and S=1 State in Solution.

The [FeIV (O)(Me3 NTB)]2+ (Me3 NTB=tris[(1-methyl-benzimidazol-2-yl)methyl]amine) complex 1 has been shown by Mössbauer spectroscopy to have an S=1 ground state at 4 K, but is proposed to become an S=2 trigonal-bipyramidal species at higher temperatures based on a DFT model to rationalize its very high C-H bond-cleavage reactivity. In this work, 1 H NMR spectroscopy was used to determine that 1 does not have C3 -symmetry in solution and is not an S=2 species. Our results show that 1 is unique among nonheme FeIV =O complexes in retaining its S=1 spin state and high reactivity at 193 K, providing evidence that S=1 FeIV =O complexes can be as reactive as their S=2 counterparts. This result emphasizes the need to identify factors besides the ground spin state of the FeIV =O center to rationalize nonheme oxoiron(IV) reactivity.

Carboxylate Structural Effects on the Properties and Proton-Coupled Electron Transfer Reactivity of [CuO2CR]2+ Cores.

A series of complexes {[NBu4][LCuII(O2CR)] (R = -C6F5, -C6H4(NO2), -C6H5, -C6H4(OMe), -CH3, and -C6H2(iPr)3)} were characterized (with the complex R = -C6H4(m-Cl) having been published elsewhere ( Mandal et al. J. Am. Chem. Soc. 2019 , 141 , 17236 )). All feature N,N',N″-coordination of the supporting L2- ligand, except for the complex with R = -C6H2(iPr)3, which exhibits N,N',O-coordination. For the N,N',N″-bound complexes, redox properties, UV-vis ligand-to-metal charge transfer (LMCT) features, and rates of hydrogen atom abstraction from 2,4,6,-tri-t-butylphenol using the oxidized, formally Cu(III) compounds LCuIII(O2CR) correlated well with the electron donating nature of R as measured both experimentally and computationally. Specifically, the greater the electron donation, the lower is the energy for LMCT and the slower is the reaction rate. The results are interpreted to support an oxidatively asynchronous proton-coupled electron transfer mechanism that is sensitive to the oxidative power of the [CuIII(O2CR)]2+ core.

Activation of a Non-Heme FeIII -OOH by a Second FeIII to Hydroxylate Strong C-H Bonds: Possible Implications for Soluble Methane Monooxygenase.

Non-heme iron oxygenases contain either monoiron or diiron active sites, and the role of the second iron in the latter enzymes is a topic of particular interest, especially for soluble methane monooxygenase (sMMO). Herein we report the activation of a non-heme FeIII -OOH intermediate in a synthetic monoiron system using FeIII (OTf)3 to form a high-valent oxidant capable of effecting cyclohexane and benzene hydroxylation within seconds at -40 °C. Our results show that the second iron acts as a Lewis acid to activate the iron-hydroperoxo intermediate, leading to the formation of a powerful FeV =O oxidant-a possible role for the second iron in sMMO.