10-Fold Increase in Hydrogen Atom Transfer Reactivity for a Series of = 1 Fe═O Complexes Over the = 2 [(TQA)Fe═O] Complex via Entropic Lowering of Reaction Barriers by Secondary Sphere Cycloalkyl Substitution.

Nonheme iron enzymes utilize = 2 iron(IV)-oxo intermediates as oxidants in biological oxygenations. In contrast, corresponding synthetic nonheme Fe═O complexes characterized to date favor the = 1 ground state that generally shows much poorer oxidative reactivity than their = 2 counterparts. However, one intriguing exception found by Nam a decade ago is the = 1 [Fe(O)(MeNTB)] complex (MeNTB = [tris((-methyl-benzimidazol-2-yl)methyl)amine], ) with a hydrogen atom transfer (HAT) reactivity that is 70% that of the = 2 [Fe(O)(TQA)] complex (TQA = tris(2-quinolylmethyl)amine, ).

Experimental Definition of the = 1 π vs = 2 σ Reactivity and = 2 Character in the Ground State of an = 1 FeO Complex.

Iron(IV)-oxo intermediates found in iron enzymes and artificial catalysts are competent for H atom abstraction in catalytic cycles. For = 2 intermediates, both axial and equatorial approaches are well-established. The mechanism for = 1 sites is not as well understood: an equatorial approach is more energetically favorable, and an axial approach requires crossing from the = 1 to the = 2 surface.

Preparation and characterization of MnMn complexes with relevance to class Ib ribonucleotide reductases.

The Mn complex [Mn(TPDP)(OCPh)](BPh) (1, TPDP = 1,3-bis(bis(pyridin-2-ylmethyl)amino)propan-2-ol, Ph =phenyl) was prepared and subsequently characterized via single-crystal X-ray diffraction, X-ray absorption, electronic absorption, and infrared spectroscopies, and mass spectrometry. 1 was prepared in order to explore its properties as a structural and functional mimic of class Ib ribonucleotide reductases (RNRs). 1 reacted with superoxide anion (O) to generate a peroxido-MnMn complex, 2.

A tale of two topological isomers: Uptuning [Fe(O)(Mecyclam)] for olefin epoxidation.

TMC- and TMC- the two topological isomers of [Fe(O)(TMC)(CHCN)] (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane, or Mecyclam), differ in the orientations of their Fe=O units relative to the four methyl groups of the TMC ligand framework. The Fe=O unit of TMC- points away from the four methyl groups, while that of TMC- is surrounded by the methyl groups, resulting in differences in their oxidative reactivities. TMC- reacts with HAT (hydrogen atom transfer) substrates at 1.

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

= 2 Fe═O centers generated in the active sites of nonheme iron oxygenases cleave substrate C-H bonds at rates significantly faster than most known synthetic Fe═O complexes. Unlike the majority of the latter, which are = 1 complexes, [Fe(O)(tris(2-quinolylmethyl)amine)(MeCN)] () is a rare example of a synthetic = 2 Fe═O complex that cleaves C-H bonds 1000-fold faster than the related [Fe(O)(tris(pyridyl-2-methyl)amine)(MeCN)] complex (). To rationalize this significant difference, a systematic comparison of properties has been carried out on and as well as related complexes and with mixed pyridine (Py)/quinoline (Q) ligation.

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

In the postulated catalytic cycle of class Ib Mn ribonucleotide reductases (RNRs), a Mn core is suggested to react with superoxide (O) to generate peroxido-MnMn and oxo-MnMn entities prior to proton-coupled electron transfer (PCET) oxidation of tyrosine. There is limited experimental support for this mechanism. We demonstrate that [Mn(BPMP)(OAc)](ClO) (, HBPMP = 2,6-bis[(bis(2 pyridylmethyl)amino)methyl]-4-methylphenol) was converted to peroxido-MnMn () in the presence of superoxide anion that converted to (μ-O)(μ-OH)MnMn () via the addition of an H-donor (TsOH) or (μ-O)MnMn () upon warming to room temperature.

10-fold faster C-H bond hydroxylation by a Co(µ-O) complex [via a Co(µ-O)(µ-OH) intermediate] versus its FeFe analog.

The hydroxylation of C-H bonds can be carried out by the high-valent Co(µ-O) complex supported by the tetradentate tris(2-pyridylmethyl)amine ligand via a Co(µ-O)(µ-OH) intermediate (). Complex can be independently generated either by H-atom transfer (HAT) in the reaction of with phenols as the H-atom donor or protonation of its conjugate base, the Co(µ-O) complex . Resonance Raman spectra of these three complexes reveal oxygen-isotope-sensitive vibrations at 560 to 590 cm associated with the symmetric Co-O-Co stretching mode of the CoO diamond core.

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)(NO ) ] adduct (2) by the reaction of (BnTPEN)Mn(II) (1) with 4 eq. ceric ammonium nitrate.

Explorations of the nonheme high-valent iron-oxo landscape: crystal structure of a synthetic complex with an [FeIV2(μ-O)] 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 O 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 O 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.

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 HO catalyzed by [Fe(IndH)(CHCN)](ClO) [IndH = 1,3-bis(2'-pyridylimino)isoindoline], involving a spectroscopically characterized (μ-oxo)(μ-1,2-peroxo)diiron(III) intermediate () that is capable of olefin epoxidation and alkane hydroxylation including cyclohexane. Species 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 HO 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.

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 [Fe (O )(Bn3MC)] (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 Fe -OAr product 3. At the same time, the Fe (Bn3MC) (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 [Fe (O)(L )] (2-syn)→2 [Fe (L )] (3)+[Fe (L )] (1)+H O.

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.

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] (TPA=tris(2-pyridylmethyl)amine) belong to the most reactive ones. Here, we show a fine-tuning of the reactivity of [(TPA)FeO] by an additional ligand X (X=CH CN, CF SO , ArI, and ArIO; ArI=2-( BuSO )C H I) attached in solution and reveal a thus far unknown role of the ArIO oxidant.

Ce - and HClO -Promoted Assembly of an Fe (μ-O) Diamond Core from its Monomeric Fe =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*)Fe (1) (TPA*=tris(3,5-dimethyl-4-methoxypyridyl-2-methyl)amine) in CH CN with 4 equiv CAN and 200 equiv HClO at 20 °C to form a complex with an [Fe (μ-O) ] core.

Octahedral iron(iv)-tosylimido complexes exhibiting single electron-oxidation reactivity.

High valent iron species are very reactive molecules involved in oxidation reactions of relevance to biology and chemical synthesis. Herein we describe iron(iv)-tosylimido complexes [Fe(NTs)(MePytacn)](OTf) () and [Fe(NTs)(Me(CHPy)tacn)](OTf) (), (MePytacn = -methyl-,-bis(2-picolyl)-1,4,7-triazacyclononane, and Me(CHPy)tacn = 1-(di(2-pyridyl)methyl)-4,7-dimethyl-1,4,7-triazacyclononane, Ts = Tosyl). and are rare examples of octahedral iron(iv)-imido complexes and are isoelectronic analogues of the recently described iron(iv)-oxo complexes [Fe(O)(L)] (L = MePytacn and Me(CHPy)tacn, respectively).

Sc-Promoted O-O Bond Cleavage of a (μ-1,2-Peroxo)diiron(III) Species Formed from an Iron(II) Precursor and O to Generate a Complex with an Fe(μ-O) 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 () from the oxygenation of the diiron(II) enzyme and its subsequent conversion to , the diiron(IV) oxidant that hydroxylates methane. Synthetic diiron(IV) complexes that can serve as models for are rare and have not been generated by a reaction sequence analogous to that of sMMO. In this work, we show that [Fe(MeNTB)(CHCN)](CFSO) (MeNTB = tris((1-methyl-1-benzo[d]imidazol-2-yl)methyl)amine) () reacts with O in the presence of base, generating a (μ-1,2-peroxo)diiron(III) adduct with a low O-O stretching frequency of 825 cm and a short Fe···Fe distance of 3.

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

A series of complexes {[NBu][LCu(OCR)] (R = -CF, -CH(NO), -CH, -CH(OMe), -CH, and -CH(Pr))} were characterized (with the complex R = -CH(m-Cl) having been published elsewhere ( Mandal et al. 2019 , 141 , 17236 )). All feature -coordination of the supporting L ligand, except for the complex with R = -CH(Pr), which exhibits -coordination.

Acid p Dependence in O-O Bond Heterolysis of a Nonheme Fe-OOH Intermediate To Form a Potent Fe═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 = 1/2 Fe-OOH species [(BnTPEN)Fe(OOH)] (, BnTPEN = -benzyl--tris(2-pyridylmethyl)-1,2-diaminoethane). Addition of acids having p values of >8.

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 PyNMe ligand. A complete spectroscopic characterization of the oxoiron(IV) species () reveals that this compound exists as a mixture of two isomers. The reactivity of the thermodynamically more stable oxoiron(IV) isomer () is directly compared to that exhibited by the previously reported 1e-oxidized analogue [Fe(O)(OAc)(PyNMe)] ().

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.

Structural implications of the paramagnetically shifted NMR signals from pyridine H atoms on synthetic nonheme Fe=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 H-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.

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

The [Fe (O)(Me NTB)] (Me 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, H NMR spectroscopy was used to determine that 1 does not have C -symmetry in solution and is not an S=2 species. Our results show that 1 is unique among nonheme Fe =O complexes in retaining its S=1 spin state and high reactivity at 193 K, providing evidence that S=1 Fe =O complexes can be as reactive as their S=2 counterparts.

Activation of a Non-Heme Fe -OOH by a Second Fe 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 Fe -OOH intermediate in a synthetic monoiron system using Fe (OTf) 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 Fe =O oxidant-a possible role for the second iron in sMMO.