Heterolytic O-O Bond Cleavage Upon Single Electron Transfer to a Nonheme Fe(III)-OOH Complex.

The one-electron reduction of the nonheme iron(III)-hydroperoxo complex, [FeIII (OOH)(L5 2 )]2+ (L5 2 =N-methyl-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine), carried out at -70 °C results in the release of dioxygen and in the formation of [FeII (OH)(L5 2 )]+ following a bimolecular process. This reaction can be performed either with cobaltocene as chemical reductant, or electrochemically. These experimental observations are consistent with the disproportionation of the hydroperoxo group in the putative FeII (OOH) intermediate generated upon reduction of the FeIII (OOH) starting complex. One plausible mechanistic scenario is that this disproportionation reaction follows an O-O heterolytic cleavage pathway via a FeIV -oxo species.

A Tale of Two Complexes: Electro-Assisted Oxidation of Thioanisole by an "O2 Activator/Oxidizing Species" Tandem System of Non-Heme Iron Complexes.

We report two new FeIII complexes [L1 FeIII (H2 O)](OTf)2 and [L2 FeIII (OTf)], obtained by replacing pyridines by phenolates in a known non-heme aminopyridine iron complex. While the original, starting aminopyridine [(L5 2 )FeII (MeCN)](PF6 ) complex is stable in air, the potentials of the new FeIII/II couples decrease to the point that [L2 FeII ] spontaneously reduces O2 to superoxide. We used it as an O2 activator in an electrochemical setup, as its presence allows to generate superoxide at a much more accessible potential (>500 mV gain). Our aim was to achieve substrate oxidation via the reductive activation of O2 . While L2 FeIII (OTf) proved to be a good O2 activator but a poor oxidation system, its association with another complex (TPEN)FeII (PF6 )2 generates a complementary tandem couple for electro-assisted oxidation of substrates, working at a very accessible potential: upon reduction, L2 FeIII (OTf) activates O2 to superoxide and transfers it to (TPEN)FeII (PF6 )2 leading in fine to the oxidation of thioanisole.

Hydroxylation of Aromatics by H2 O2 Catalyzed by Mononuclear Non-heme Iron Complexes: Role of Triazole Hemilability in Substrate-Induced Bifurcation of the H2 O2 Activation Mechanism.

Rieske dioxygenases are metalloenzymes capable of achieving cis-dihydroxylation of aromatics under mild conditions using O2 and a source of electrons. The intermediate responsible for this reactivity is proposed to be a cis-FeV (O)(OH) moiety. Molecular models allow the generation of a FeIII (OOH) species with H2 O2 , to yield a FeV (O)(OH) species with tetradentate ligands, or {FeIV (O); OH. } pairs with pentadentate ones. We have designed a new pentadentate ligand, mtL4 2 , bearing a labile triazole, to generate an "in-between" situation. Two iron complexes, [(mtL4 2 )FeCl](PF6 ) and [(mtL4 2 )Fe(OTf)2 ]), were obtained and their reactivity towards aromatic substrates was studied in the presence of H2 O2 . Spectroscopic and kinetic studies reflect that triazole is bound at the FeII state, but decoordinates in the FeIII (OOH). The resulting [(mtL4 2 )FeIII (OOH)(MeCN)]2+ then lies on a bifurcated decay pathway (end-on homolytic vs. side-on heterolytic) depending on the addition of aromatic substrate: in the absence of substrate, it is proposed to follow a side-on pathway leading to a putative (N4 )FeV (O)(OH), while in the presence of aromatics it switches to an end-on homolytic pathway yielding a {(N5 )FeIV (O); OH. } reactive species, through recoordination of triazole. This switch significantly impacts the reaction regioselectivity.

FeIII and FeII Phosphasalen Complexes: Synthesis, Characterization, and Catalytic Application for 2-Naphthol Oxidative Coupling.

We report on the synthesis and characterization of three iron(III) phosphasalen complexes, [FeIII (Psalen)(X)] differing in the nature of the counter-anion/exogenous ligand (X- =Cl- , NO3 - , OTf- ), as well as the neutral iron(II) analogue, [FeII (Psalen)]. Phosphasalen (Psalen) differs from salen by the presence of iminophosphorane (P=N) functions in place of the imines. All the complexes were characterized by single-crystal X-ray diffraction, UV/Vis, EPR, and cyclic voltammetry. The [FeII (Psalen)] complex was shown to remain tetracoordinated even in coordinating solvent but surprisingly exhibits a magnetic moment in line with a FeII high-spin ground state. For the FeIII complexes, the higher lability of triflate anion compared to nitrate was demonstrated. As they exhibit lower reduction potentials compared to their salen analogues, these complexes were tested for the coupling of 2-naphthol using O2 from air as oxidant. In order to shed light on this reaction, the interaction between 2-naphthol and the FeIII (Psalen) complexes was studied by cyclic voltammetry as well as UV/Vis spectroscopy.

Non-Heme FeII Diastereomeric Complexes Bearing a Hexadentate Ligand: Unexpected Consequences for the Spin State and Catalytic Oxidation Properties.

The reactivity and selectivity of non-heme FeII complexes as oxidation catalysts can be substantially modified by alteration of the ligand backbone or introduction of various substituents. In comparison with the hexadentate ligand N,N,N',N'-tetrakis(pyridin-2-ylmethyl)ethane-1,2-diamine (TPEN), N,N'-bis[1-(pyridin-2-yl)ethyl]-N,N'-bis(pyridin-2-ylmethyl)ethane-1,2-diamine (2Me L6 2 ) has a methyl group on two of the four picolyl positions. FeII complexation by 2Me L6 2 yields two diastereomeric complexes with very similar structures, which only differ in the axial/equatorial positions occupied by the methylated pyridyl groups. In solution, these two isomers exhibit different magnetic behaviors. Whereas one isomer exhibits temperature-dependent spin-state conversion between the S=0 and S=2 states, the other is more reluctant towards this spin-state equilibrium and is essentially diamagnetic at room temperature. Their catalytic properties for the oxidation of anisole by H2 O2 are very different and correlate with their magnetic properties, which reflect their lability/inertness. These different properties most likely depend on the different steric constraints of the methylated pyridyl groups in the two complexes.

A Reversible Electron Relay to Exclude Sacrificial Electron Donors in the Photocatalytic Oxygen Atom Transfer Reaction with O2 in Water.

Using light energy and O2 for the direct chemical oxidation of organic substrates is a major challenge. A limitation is the use of sacrificial electron donors to activate O2 by reductive quenching of the photosensitizer, generating undesirable side products. A reversible electron acceptor, methyl viologen, can act as electron shuttle to oxidatively quench the photosensitizer, [Ru(bpy)3 ]2+ , generating the highly oxidized chromophore and the powerful reductant methyl-viologen radical MV+. . MV+. can then reduce an iron(III) catalyst to the iron(II) form and concomitantly O2 to O2.- in an aqueous medium to generate an active iron(III)-(hydro)peroxo species. The oxidized photosensitizer is reset to its ground state by oxidizing an alkene substrate to an alkenyl radical cation. Closing the loop, the reaction of the iron reactive intermediate with the substrate or its radical cation leads to the formation of two oxygenated compounds, the diol and the aldehyde following two different pathways.

Selective Formation of an FeIV O or an FeIII OOH Intermediate From Iron(II) and H2 O2 : Controlled Heterolytic versus Homolytic Oxygen-Oxygen Bond Cleavage by the Second Coordination Sphere.

We demonstrate that the devised incorporation of an alkylamine group into the second coordination sphere of an FeII complex allows to switch its reactivity with H2 O2 from the usual formation of FeIII species towards the selective generation of an FeIV -oxo intermediate. The FeIV -oxo species was characterized by UV/Vis absorption and Mössbauer spectroscopy. Variable-temperature kinetic analyses point towards a mechanism in which the heterolytic cleavage of the O-O bond is triggered by a proton transfer from the proximal to the distal oxygen atom in the FeII -H2 O2 complex with the assistance of the pendant amine. DFT studies reveal that this heterolytic cleavage is actually initiated by an homolytic O-O cleavage immediately followed by a proton-coupled electron transfer (PCET) that leads to the formation of the FeIV -oxo and release of water through a concerted mechanism.

Mimicking the Regulation Step of Fe-Monooxygenases: Allosteric Modulation of FeIV -Oxo Formation by Guest Binding in a Dinuclear ZnII -FeII Calix[6]arene-Based Funnel Complex.

A heteroditopic ligand associated with a calix[6]arene scaffold bearing a tris(imidazole) coordinating site at its small rim and an amine/pyridine ligand at its large rim has been prepared, and its regioselective coordination to ZnII at the small rim and FeII in the amine/pyridine ligand has been achieved. The heterodinuclear complex obtained displays an overall cone conformation capped by the tris(imidazole)ZnII moiety and bears a non-heme FeII complex at its base. Each of the metal centers exhibits one labile position, allowing the coordination inside the cavity of a guest alkylamine at ZnII and the generation of reaction intermediates (FeIII (OOH) and FeIV O) at the large rim. A dependence between the chain length of the encapsulated alkylamine and the distribution of FeIII (OOH) intermediates and FeIII (OMe) is observed. In addition, it is shown that the generation of the FeIV O intermediate is enhanced by addition of the alkylamine guest. Hence, this supramolecular system gathers the three levels of reactivity control encountered in oxidoreductases: i) control of the FeII redox properties through its first coordination sphere, allowing us to generate high valent reactive species; ii) control of guest binding through a hydrophobic funnel that drives its alkyl chain next to the reactive iron complex, thus mimicking the binding pocket of natural systems; iii) guest-modulated reactivity of the FeII center towards oxidants.

Arene activation by a nonheme iron(III)-hydroperoxo complex: pathways leading to phenol and ketone products.

Iron(III)-hydroperoxo complexes are found in various nonheme iron enzymes as catalytic cycle intermediates; however, little is known on their catalytic properties. The recent work of Banse and co-workers on a biomimetic nonheme iron(III)-hydroperoxo complex provided evidence of its involvement in reactivity with arenes. This contrasts the behavior of heme iron(III)-hydroperoxo complexes that are known to be sluggish oxidants. To gain insight into the reaction mechanism of the biomimetic iron(III)-hydroperoxo complex with arenes, we performed a computational (density functional theory) study. The calculations show that iron(III)-hydroperoxo reacts with substrates via low free energies of activation that should be accessible at room temperature. Moreover, a dominant ketone reaction product is observed as primary products rather than the thermodynamically more stable phenols. These product distributions are analyzed and the calculations show that charge interaction between the iron(III)-hydroxo group and the substrate in the intermediate state pushes the transferring proton to the meta-carbon atom of the substrate and guides the selectivity of ketone formation. These studies show that the relative ratio of ketone versus phenol as primary products can be affected by external interactions of the oxidant with the substrate. Moreover, iron(III)-hydroperoxo complexes are shown to selectively give ketone products, whereas iron(IV)-oxo complexes will react with arenes to form phenols instead.

Characterization and Subsequent Reactivity of an Fe-Peroxo Porphyrin Generated by Electrochemical Reductive Activation of O2.

Reductive activation of O2 is achieved by using the [FeIII(F20TPP)Cl] (F20TPP = 5,10,15,20-tetrakis(pentafluorophenyl) porphyrinate) porphyrin through electrochemical reduction of the [FeIII(F20TPP)(O2•-)] superoxo complex. Formation of the [FeIII(F20TPP)(OO)]- peroxo species is monitored by using low-temperature electronic absorption spectroscopy, electron paramagnetic resonance, and cyclic voltammetry. Its subsequent protonation to yield the [FeIII(F20TPP)(OOH)] hydroperoxo intermediate is probed using low-temperature electronic absorption spectroscopy and electron paramagnetic resonance.

Differences and comparisons of the properties and reactivities of iron(III)-hydroperoxo complexes with saturated coordination sphere.

Heme and nonheme monoxygenases and dioxygenases catalyze important oxygen atom transfer reactions to substrates in the body. It is now well established that the cytochrome P450 enzymes react through the formation of a high-valent iron(IV)-oxo heme cation radical. Its precursor in the catalytic cycle, the iron(III)-hydroperoxo complex, was tested for catalytic activity and found to be a sluggish oxidant of hydroxylation, epoxidation and sulfoxidation reactions. In a recent twist of events, evidence has emerged of several nonheme iron(III)-hydroperoxo complexes that appear to react with substrates via oxygen atom transfer processes. Although it was not clear from these studies whether the iron(III)-hydroperoxo reacted directly with substrates or that an initial O-O bond cleavage preceded the reaction. Clearly, the catalytic activity of heme and nonheme iron(III)-hydroperoxo complexes is substantially different, but the origins of this are still poorly understood and warrant a detailed analysis. In this work, an extensive computational analysis of aromatic hydroxylation by biomimetic nonheme and heme iron systems is presented, starting from an iron(III)-hydroperoxo complex with pentadentate ligand system (L5(2)). Direct C-O bond formation by an iron(III)-hydroperoxo complex is investigated, as well as the initial heterolytic and homolytic bond cleavage of the hydroperoxo group. The calculations show that [(L5(2))Fe(III)(OOH)](2+) should be able to initiate an aromatic hydroxylation process, although a low-energy homolytic cleavage pathway is only slightly higher in energy. A detailed valence bond and thermochemical analysis rationalizes the differences in chemical reactivity of heme and nonheme iron(III)-hydroperoxo and show that the main reason for this particular nonheme complex to be reactive comes from the fact that they homolytically split the O-O bond, whereas a heterolytic O-O bond breaking in heme iron(III)-hydroperoxo is found.

An Artificial Enzyme Made by Covalent Grafting of an Fe(II) Complex into ß-Lactoglobulin: Molecular Chemistry, Oxidation Catalysis, and Reaction-Intermediate Monitoring in a Protein.

An artificial metalloenzyme based on the covalent grafting of a nonheme Fe(II) polyazadentate complex into bovine ß-lactoglobulin has been prepared and characterized by using various spectroscopic techniques. Attachment of the Fe(II) catalyst to the protein scaffold is shown to occur specifically at Cys121. In addition, spectrophotometric titration with cyanide ions based on the spin-state conversion of the initial high spin (S=2) Fe(II) complex into a low spin (S=0) one allows qualitative and quantitative characterization of the metal center's first coordination sphere. This biohybrid catalyst activates hydrogen peroxide to oxidize thioanisole into phenylmethylsulfoxide as the sole product with an enantiomeric excess of up to 20 %. Investigation of the reaction between the biohybrid system and H2 O2 reveals the generation of a high spin (S=5/2) Fe(III) (η(2) -O2 ) intermediate, which is proposed to be responsible for the catalytic sulfoxidation of the substrate.

Assessment of new hydrogen peroxide activators in water and comparison of their active species toward contaminants of emerging concern.

Advanced oxidation processes are the most efficient tool to thwart the overaccumulation of harmful organic compounds in the environment. In this direction bioinspired metal complexes may be a viable solution for oxidative degradations in water. However, their synthesis is often elaborated and their scalability consequently low. This study presents alternative easy-to-synthesize bioinspired metal complexes to promote degradations in water. The metals employed were iron and manganese ions, hence cheap and highly accessible ions. The complexes were tested toward Phenol, Estrone, Triclosan, Oxybenzone, Diclofenac, Carbamazepine, Erythromycin, Aspartame, Acesulfame K, Anisole and 2,4-Dinitrotoluene. The reaction favoured electron-rich compounds reaching a removal efficiency of over 90%. The central ion plays a crucial role. Specifically, Mn(II) induces a non-radical pathway while iron ions a predominant radical one (⋅OH is predominant). The iron systems resulted more versatile toward contaminants, while the manganese ones showed a higher turn-over number, hence higher catalytic behaviour.

Iron coordination chemistry with new ligands containing triazole and pyridine moieties. Comparison of the coordination ability of the N-donors.

We report the synthesis, characterization, and solution chemistry of a series of new Fe(II) complexes based on the tetradentate ligand N-methyl-N,N'-bis(2-pyridyl-methyl)-1,2-diaminoethane or the pentadentate ones N,N',N'-tris(2-pyridyl-methyl)-1,2-diaminoethane and N,N',N'-tris(2-pyridyl-methyl)-1,3-diaminopropane, modified by propynyl or methoxyphenyltriazolyl groups on the amino functions. Six of these complexes are characterized by X-ray crystallography. In particular, two of them exhibit an hexadentate coordination environment around Fe(II) with two amino, three pyridyl, and one triazolyl groups. UV-visible and cyclic voltammetry experiments of acetonitrile solutions of the complexes allow to deduce accurately the structure of all Fe(II) species in equilibrium. The stability of the complexes could be ranked as follows: [L(5)Fe(II)-py](2+) > [L(5)Fe(II)-Cl](+) > [L(5)Fe(II)-triazolyl](2+) > [L(5)Fe(II)-(NCMe)](2+), where L(5) designates a pentadentate coordination sphere composed of the two amines of ethanediamine and three pyridines. For complexes based on propanediamine, the hierarchy determined is [L(5)Fe(II)-Cl](+) > [L(5)Fe(II)(OTf)](+) > [L(5)Fe(II)-(NCMe)](2+), and no ligand exchange could be evidenced for [L(5)Fe(II)-triazolyl](2+). Reactivity of the [L(5)Fe(II)-triazolyl](2+) complexes with hydrogen peroxide and PhIO is similar to the one of the parent complexes that lack this peculiar group, that is, generation of Fe(III)(OOH) and Fe(IV)(O), respectively. Accordingly, the ability of these complexes at catalyzing the oxidation of small organic molecules by these oxidants follows the tendencies of their previously reported counterparts. Noteworthy is the remarkable cyclooctene epoxidation activity by these complexes in the presence of PhIO.

Catalytic oxidation properties of an acid-resistant cross-bridged cyclen Fe(II) complex. Influence of the rigid donor backbone and protonation on the reactivity.

The catalytic properties of an iron complex bearing a pentadentate cross-bridged ligand backbone are reported. With H2O2 as an oxidant, it displays moderate conversions in epoxidation and alkane hydroxylation and satisfactory ones in aromatic hydroxylation. Upon addition of an acid to the reaction medium, a significant enhancement in aromatic and alkene oxidation is observed. Spectroscopic analyses showed that accumulation of the expected FeIII(OOH) intermediate is limited under these conditions, unless an acid is added to the mixture. This is ascribed to the inertness induced by the cross-bridged ligand backbone, which is partly reduced under acidic conditions.

Hydroxylation of aromatics with the help of a non-haem FeOOH: a mechanistic study under single-turnover and catalytic conditions.

Ferric-hydroperoxo complexes have been identified as intermediates in the catalytic cycle of biological oxidants, but their role as key oxidants is still a matter of debate. Among the numerous synthetic low-spin Fe(III)(OOH) complexes characterized to date, [(L(5)(2))Fe(OOH)](2+) is the only one that has been isolated in the solid state at low temperature, which has provided a unique opportunity for inspecting its oxidizing properties under single-turnover conditions. In this report we show that [(L(5)(2))Fe(OOH)](2+) decays in the presence of aromatic substrates, such as anisole and benzene in acetonitrile, with first-order kinetics. In addition, the phenol products are formed from the aromatic substrates with similar first-order rate constants. Combining the kinetic data obtained at different temperatures and under different single-turnover experimental conditions with experiments performed under catalytic conditions by using the substrate [1,3,5-D(3)]benzene, which showed normal kinetic isotope effects (KIE>1) and a notable hydride shift (NIH shift), has allowed us to clarify the role played by Fe(III)(OOH) in aromatic oxidation. Several lines of experimental evidence in support of the previously postulated mechanism for the formation of two caged Fe(IV)(O) and OH(·) species from the Fe(III)(OOH) complex have been obtained for the first time. After homolytic O-O cleavage, a caged pair of oxidants [Fe(IV)O+HO(·)] is generated that act in unison to hydroxylate the aromatic ring: HO(·) attacks the ring to give a hydroxycyclohexadienyl radical, which is further oxidized by Fe(IV)O to give a cationic intermediate that gives rise to a NIH shift upon ketonization before the final re-aromatization step. Spin-trapping experiments in the presence of 5,5-dimethyl-1-pyrroline N-oxide and GC-MS analyses of the intermediate products further support the proposed mechanism.

Photocatalytic generation of a non-heme Fe(iii)-hydroperoxo species with O2 in water for the oxygen atom transfer reaction.

Coupling a photoredox module and a bio-inspired non-heme model to activate O2 for the oxygen atom transfer (OAT) reaction requires a vigorous investigation to shed light on the multiple competing electron transfer steps, charge accumulation and annihilation processes, and the activation of O2 at the catalytic unit. We found that the efficient oxidative quenching mechanism between a [Ru(bpy)3]2+ chromophore and a reversible electron mediator, methyl viologen (MV2+), to form the reducing species methyl viologen radical (MV˙+) can convey an electron to O2 to form the superoxide radical and reset an Fe(iii) species in a catalytic cycle to the Fe(ii) state in an aqueous solution. The formation of the Fe(iii)-hydroperoxo (FeIII-OOH) intermediate can evolve to a highly oxidized iron-oxo species to perform the OAT reaction to an alkene substrate. Such a strategy allows us to bypass the challenging task of charge accumulation at the molecular catalytic unit for the two-electron activation of O2. The FeIII-OOH catalytic precursor was trapped and characterized by EPR spectroscopy pertaining to a metal assisted catalysis. Importantly, we found that the substrate itself can act as an electron donor to reset the photooxidized chromophore in the initial state closing the photocatalytic loop and hence excluding the use of a sacrificial electron donor. Laser Flash Photolysis (LFP) studies and spectroscopic monitoring during photocatalysis lend credence to the proposed catalytic cycle.

Modulating alkene reactivity from oxygenation to halogenation via electrochemical O2 activation by Mn porphyrin.

Oxidation of organic substrates is achieved in nature under mild conditions thanks to metalloenzymes but remains a challenge for chemists. Herein we show by UV-Vis spectroelectrochemistry that when MnIIITPPCl is electrochemically reduced to MnII in CH2Cl2 under O2, a MnIIO2˙ species is generated. Benzoic anhydride reacts with the latter triggering a catalytic current in cyclic voltammetry. Electrolysis on the catalytic wave in the presence of cyclooctene leads to its oxygenation or halogenation depending on the axial ligand present as reported here for the first time.

Second-sphere effects on H2O2 activation by non-heme FeII complexes: role of a phenol group in the [H2O2]-dependent accumulation of FeIVO vs. FeIIIOOH.

Redox metalloenzymes achieve very selective oxidation reactions under mild conditions using O2 or H2O2 as oxidants and release harmless side-products like water. Their oxidation selectivity is intrinsically linked to the control of the oxidizing species generated during the catalytic cycle. To do so, a second coordination sphere is used in order to create a pull effect during the activation of O2 or H2O2, thus ensuring a heterolytic O-O bond cleavage. Herein, we report the synthesis and study of a new non-heme FeII complex bearing a pentaazadentate first coordination sphere and a pendant phenol group. Its reaction with H2O2 generates the classical FeIIIOOH species at high H2O2 loading. But at low H2O2 concentrations, an FeIVO species is generated instead. The formation of the latter is directly related to the presence of the 2nd sphere phenol group. Kinetic, variable temperature and labelling studies support the involvement of the attached phenol as a second coordination sphere moiety (weak acid) during H2O2 activation. Our results suggest a direct FeII → FeIVO conversion directed by the 2nd sphere phenol via the protonation of the distal O atom of the FeII/H2O2 adduct leading to a heterolytic O-O bond cleavage.

Tracking light-induced electron transfer toward O2 in a hybrid photoredox-laccase system.

Photobiocatalysis uses light to perform specific chemical transformations in a selective and efficient way. The intention is to couple a photoredox cycle with an enzyme performing multielectronic catalytic activities. Laccase, a robust multicopper oxidase, can be envisioned to use dioxygen as a clean electron sink when coupled to an oxidation photocatalyst. Here, we provide a detailed study of the coupling of a [Ru(bpy)3]2+ photosensitizer to laccase. We demonstrate that efficient laccase reduction requires an electron relay like methyl viologen. In the presence of dioxygen, electrons transiently stored in superoxide ions are scavenged by laccase to form water instead of H2O2. The net result is the photo accumulation of highly oxidizing [Ru(bpy)3]3+. This study provides ground for the use of laccase in tandem with a light-driven oxidative process and O2 as one-electron transfer relay and as four-electron substrate to be a sustainable final electron acceptor in a photocatalytic process.