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

Fe^III–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 Fe^III–hypohalite intermediates of possible relevance to iron halogenases. We show that Fe^III‐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 Fe^III‐OCl, and ultimately Fe^IV?O, species and provide indirect evidence for a short‐lived Fe^II‐OCl intermediate. The species observed and the pathways involved offer insight into and, importantly, a spectroscopic database for the investigation of iron halogenases.     

Zero-Field Splittings and Redox Potentials in an Isostructural Series of Dinuclear FeIITiIV,FeIIITiIV, and MnIITiIV Complexes with a Face-Sharing Bridging Motive

The ligand H₆ioan has been used to synthesize the three dinuclear complexes [(ioan)Mn^IITi^IV], [(ioan)Fe^IITi^IV], and [(ioan)Fe^IIITi^IV]⁺. The face-sharing bridging mode of the three phenolates provides short M-Ti^IV distances of ≈3.0 Å. Mössbauer spectra of [(ioan)Fe^IIITi^IV]⁺ show a magnetically split six-line spectrum at 3 K in zero magnetic field demonstrating a slow magnetic relaxation. Magnetic measurements provide a zero-field splitting of |D|=5 cm⁻¹ in [(ioan)Fe^IITi^IV]. EPR spectroscopy demonstrates sizable zero-field splittings of the S=5/2 spin systems of [(ioan)Mn^IITi^IV] (D=0.246 cm⁻¹) and [(ioan)Fe^IIITi^IV]⁺ (D<−1 cm⁻¹) that can be related to enforced covalency of the M-O^ph bonds. [(ioan)Fe^IIITi^IV]⁺ exhibits a reversible reduction at −0.26 V vs. Fc⁺/Fc demonstrating the facile accessibility of Fe^III and Fe^II. In contrast to an irreversible oxidation in [(ioan)Ni^IITi^IV] at 0.78 V vs. Fc⁺/Fc, the reversible oxidation at 0.25 V vs. Fc⁺/Fc in [(ioan)Mn^IITi^IV] indicates even the access of Mn^III. These results indicate that pentanuclear complexes [(ioan)FeM¹M²M¹Fe(ioan)]ⁿ⁺ are meaningful targets to access electron delocalization in mixed-valence systems over five ions due to the facile accessibility of both Fe^II and Fe^III in the terminal positions. This study provides important local spin-Hamiltonian and Mössbauer parameters that will be essential for the understanding of the potentially complicated electronic structure in the anticipated pentanuclear complexes.     

Catalytic Nitrene Transfer by an FeIV-Imido Complex Generated by a Comproportionation Process

Nitrene transfer reactions have emerged as one of the most powerful and versatile ways to insert an amine function to various kinds of hydrocarbon substrates. However, the mechanisms of nitrene generation have not been studied in depth albeit their formation is taken for granted in most cases without definitive evidence of their occurrence. In the present work, we compare the generation of tosylimido iron species and NTs transfer from Fe^II and Fe^III precursors where the metal is embedded in a tetracarbene macrocycle. Catalytic nitrene transfer to reference substrates (thioanisole, styrene, ethylbenzene and cyclohexane) revealed that the same active species was at play, irrespective of the ferrous versus ferric nature of the precursor. Through combination of spectroscopic (UV-visible, Mössbauer), ESI-MS and DFT studies, an Fe^IV tosylimido species was identified as the catalytically active species and was characterized spectroscopically and computationally. Whereas its formation from the Fe^II precursor was expected by a two-electron oxidative addition, its formation from an Fe^III precursor was unprecedented. Thanks to a combination of spectroscopic (UV-visible, EPR, Hyscore and Mössbauer), ESI-MS and DFT studies, we found that, when starting from the Fe^III precursor, an Fe^III tosyliodinane adduct was formed and decomposed into an Fe^V tosylimido species which generated the catalytically active Fe^IV tosylimide through a comproportionation process with the Fe^III precursor.     

Heat-induced changes in microstructure and magnetic properties of Co0.75Ni0.75[Fe(CN)6] · XH2O

Polycrystalline Co_0.75Ni_0.75[Fe(CN)₆]?·?XH₂O was prepared by coprecipitation. The coprecipitated powder was annealed in vacuum at 80°C, 100°C, and 130°C. Variation of microstructural and magnetic properties with different annealed temperatures was studied by Fourier-transform infrared, X-ray diffraction, and magnetization measurements. The differences in magnetic phase transition temperature, coercivity, remanence, and effective magnetization were studied in detail. The magnetic contribution mainly results from Fe^III–CN–Co^II/Ni^II and Fe^III–NC–Co^II/Ni^II because Fe^II–CN–Co^III/Ni^II carries no net spin. After annealing at 130°C, the microstructures Fe^III–CN–Co^II/Ni^II and Fe^III–NC–Co^II/Ni^II convert to Fe^II–CN–Co^III/Ni^II. Differences in magnetic properties may be attributed to heat-induced microstructural changes.     

Synthesis,Characterization, and Reactivity of a Series of Homo- and Hetero-dinuclear Complexes based on an Asymmetric FloH Ligand System

In a previous communication we reported the site-directed generation of a heterodinuclear Fe^IIICu^II complex ( 1 ) by using an asymmetric dinucleating ligand FloH. The iron(III) ion was introduced first on the preferential metal-binding site of the ligand that led to the formation of the thermodynamically favored five-membered chelate ring upon metal-binding. Copper(II) was introduced in the next step. The stepwise metalation strategy reported previously has now been extended to synthesize a series of heterodinuclear Fe^IIIM^II [M = Mn ( 2 ), Fe ( 3 ), Co ( 4 ), and Ni ( 5 )] and Fe^IICu^I ( 1a ) as well as the homodinuclear Cu^ICu^I ( 6 ) complexes. The complexes were characterized by X-ray crystallography (except for 1a and 6 ), and by a limited number of spectroscopic methods. Complex 1 with a labile solvent binding site at Fe^III reacted with H₂O₂ to form a transient intermediate that showed reactivity typical of metal peroxide complexes. The metal centers in the complexes 2 – 5 are coordinatively saturated, and hence they showed no reactivity with H₂O₂. Complex 1a reacted with O₂ via an intermolecular pathway to form a μ-oxo bridged tetrameric complex 1b , which was structurally characterized. This is in contrast to the homodinuclear Cu^ICu^I and heme Fe^IICu^I cores, which prefer an intramolecular pathway for O₂ activation.     

Bistability of an iron-cobalt binuclear complex

Bistability of the four cis/trans isomers of the proposed iron-cobalt binuclear complex [(CO)₂(benzoate-)Fe^II/III(-terephthalate-)Co^III/II(-benzoate)(CO)₂]¹⁺, arising from the Fe^II/III ↔ Co^III/II intramolecular charge transfer (IMCT) is investigated computationally at (TD)DFT-B3LYP/LanL2DZ level of theory. Energies, geometries, atomic charges, and the UV-Vis spectra are considered in this investigation. Results approve IMCT bistability of all cis/trans isomers by locating two stable states with distinctly different structures and charge distributions (Fe^II-Co^III and Fe^III-Co^II oxidation states). Also, well-defined first-order saddle points between these two IMCT states are found and characterized using QST2/QST3 method. Based on the analysis of the calculated charge distributions and the 0.35-1.66 eV activation (barrier) energies of the Fe^II-Co^III ↔ Fe^III-Co^II IMCT reactions, it can be predicted that electric field or NIR radiation may be used to switch between the two IMCT states of this bistable binuclear complex. It is also found that the cis/trans isomerization has significant effects on the energetics of this IMCT reaction, and that the trans-Fe^II/III-trans-Co^III/II isomer is the best candidate for prospective switching application due to having the least energy dissipation and the largest charge transfer.     

Comparative Study of Ruthenium(II) and Ruthenium(III) Complexes with the Ligand dmbpy (dmbpy = 4, 4′‐Dimethyl‐2, 2′‐bipyridine)

The complex cis‐[Ru^III(dmbpy)₂Cl₂](PF₆) ( 2 ) (dmbpy = 4, 4′‐dimethyl‐2, 2′‐bipyridine) was obtained from the reaction of cis‐[Ru^II(dmbpy)₂Cl₂] ( 1 ) with ammonium cerium(IV) nitrate followed by precipitation with saturated ammonium hexafluoridophosphate. The ¹H NMR spectrum of the Ru^III complex confirms the presence of paramagnetic metal atoms, whereas that of the Ru^II complex displays diamagnetism. The ³¹P NMR spectrum of the Ru^III complex shows one signal for the phosphorus atom of the PF₆^– ion. The perspective view of each [Ru^II/III(dmbpy)₂Cl₂]^0/+ unit manifests that the ruthenium atom is in hexacoordinate arrangement with two dmbpy ligands and two chlorido ligands in cis position. As the oxidation state of the central ruthenium metal atom becomes higher, the average Ru–Cl bond length decreases whereas the Ru–N (dmbpy) bond length increases. The cis‐positioned dichloro angle in Ru^III is 1.3° wider than that in the Ru^II. The dihedral angles between pair of planar six‐membered pyridyl ring in the dmbpy ligand for the Ru^II are 4.7(5)° and 5.7(4)°. The observed inter‐planar angle between two dmbpy ligands in the Ru^II is 89.08(15)°, whereas the value for the Ru^III is 85.46(20)°.     

A Heterometallic FeII–DyIII Single‐Molecule Magnet with a Record Anisotropy Barrier

A record anisotropy barrier (319 cm^?1) for all d‐f complexes was observed for a unique Fe^II‐Dy^III‐Fe^II single‐molecule magnet (SMM), which possesses two asymmetric and distorted Fe^II ions and one quasi‐D_5h Dy^III ion. The frozen magnetization of the Dy^III ion leads to the decreased Fe^II relaxation rates evident in the Mössbauer spectrum. Ab initio calculations suggest that tunneling is interrupted effectively thanks to the exchange doublets.     

Activation of Aryl and Heteroaryl Halides by an Iron(I) Complex Generated in the Reduction of [Fe(acac)3] by PhMgBr: Electron Transfer versus Oxidative Addition

The mechanism of the reactions of aryl/heteroaryl halides with aryl Grignard reagents catalyzed by [Fe^III(acac)₃] (acac=acetylacetonate) has been investigated. It is shown that in the presence of excess PhMgBr, [Fe^III(acac)₃] affords two reduced complexes: [PhFe^II(acac)(thf)_n] (n=1 or 2) (characterized by ¹H NMR and cyclic voltammetry) and [PhFe^I(acac)(thf)]^? (characterized by cyclic voltammetry, ¹H NMR, EPR and DFT). Whereas [PhFe^II(acac)(thf)_n] does not react with any of the investigated aryl or heteroaryl halides, the Fe^I complex [PhFe^I(acac)(thf)]^? reacts with ArX (Ar=Ph, 4‐tolyl; X=I, Br) through an inner‐sphere monoelectronic reduction (promoted by halogen bonding) to afford the corresponding arene ArH together with the Grignard homocoupling product PhPh. In contrast, [PhFe^I(acac)(thf)]^? reacts with a heteroaryl chloride (2‐chloropyridine) to afford the cross‐coupling product (2‐phenylpyridine) through an oxidative addition/reductive elimination sequence. The mechanism of the reaction of [PhFe^I(acac)(thf)]^? with the aryl and heteroaryl halides has been explored on the basis of DFT calculations.     

A Class of FeIII Macrocyclic Complexes with Alcohol Donor Groups as Effective T1 MRI Contrast Agents

Early studies suggested that Fe^III complexes cannot compete with Gd^III complexes as T₁ MRI contrast agents. Now it is shown that one member of a class of high‐spin macrocyclic Fe^III complexes produces more intense contrast in mice kidneys and liver at 30 minutes post‐injection than does a commercially used Gd^III agent and also produces similar T₁ relaxivity in serum phantoms at 4.7 T and 37 °C. Comparison of four different Fe^III macrocyclic complexes elucidates the factors that contribute to relaxivity in vivo including solution speciation. Variable‐temperature ¹⁷O NMR studies suggest that none of the complexes has a single, integral inner‐sphere water that exchanges rapidly on the NMR timescale. MRI studies in mice show large in vivo differences of three of the Fe^III complexes that correspond, in part, to their r₁ relaxivity in phantoms. Changes in overall charge of the complex modulate contrast enhancement, especially of the kidneys.     

Lability‐Controlled Syntheses of Heterometallic Clusters

A bulky bidentate ligand was used to stabilize a macrocyclic [Fe^III₈Co^II₆] cluster. Tuning the basicity of the ligand by derivatization with one or two methoxy groups led to the isolation of a homologous [Fe^III₈Co^II₆] species and a [Fe^III₆Fe^II₂Co^III₂Co^II₂] complex, respectively. Lowering the reaction temperatures allowed isolation of [Fe^III₆Fe^II₂Co^III₂Co^II₂] clusters with all three ligands. Temperature‐dependent absorption data and corresponding experiments with iron/nickel systems indicated that the iron/cobalt self‐assembly process was directed by the occurrence of solution‐state electron‐transfer‐coupled spin transition (ETCST) and its influence on reaction intermediate lability.     

C?H Bond Activation by Metal–Superoxo Species: What Drives High Reactivity?

Metal–superoxo species are ubiquitous in metalloenzymes and bioinorganic chemistry and are known for their high reactivity and their ability to activate inert C? H bonds. The comparative oxidative abilities of M–O₂^.? species (M=Cr^III, Mn^III, Fe^III, and Cu^II) towards C? H bond activation reaction are presented. These superoxo species generated by oxygen activation are found to be aggressive oxidants compared to their high‐valent metal–oxo counterparts generated by O???O bond cleavage. Our calculations illustrate the superior oxidative abilities of Fe^III– and Mn^III–superoxo species compared to the others and suggest that the reactivity may be correlated to the magnetic exchange parameter.     

C?H Bond Activation by Metal–Superoxo Species: What Drives High Reactivity?

Metal–superoxo species are ubiquitous in metalloenzymes and bioinorganic chemistry and are known for their high reactivity and their ability to activate inert C H bonds. The comparative oxidative abilities of M–O₂^.− species (M=Cr^III, Mn^III, Fe^III, and Cu^II) towards C H bond activation reaction are presented. These superoxo species generated by oxygen activation are found to be aggressive oxidants compared to their high‐valent metal–oxo counterparts generated by O⋅⋅⋅O bond cleavage. Our calculations illustrate the superior oxidative abilities of Fe^III– and Mn^III–superoxo species compared to the others and suggest that the reactivity may be correlated to the magnetic exchange parameter.     

Decay of Iron(V) Nitride Complexes By a NN Bond‐Coupling Reaction in Solution: A Combined Spectroscopic and Theoretical Analysis

Cryogenically trapped Fe^V nitride complexes with cyclam‐based ligands were found to decay by bimolecular reactions, forming exclusively Fe^II compounds. Characterization of educts and products by Mössbauer spectroscopy, mass spectrometry, and spectroscopy‐oriented DFT calculations showed that the reaction mechanism is reductive nitride coupling and release of dinitrogen (2 Fe^V?N→Fe^II‐N?N‐Fe^II→2 Fe^II+N₂). The reaction pathways, representing an “inverse” of the Haber–Bosch reaction, were computationally explored in detail, also to judge the feasibility of yielding catalytically competent Fe^V(N). Implications for the photolytic cleavage of Fe^III azides used to generate high‐valent Fe nitrides are discussed.     

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 Fe^III complexes [L¹Fe^III(H₂O)](OTf)₂ and [L²Fe^III(OTf)] , obtained by replacing pyridines by phenolates in a known non-heme aminopyridine iron complex. While the original, starting aminopyridine [(L₅ ² )Fe^II(MeCN)](PF₆) complex is stable in air, the potentials of the new Fe^III/II couples decrease to the point that [L²Fe^II] 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 L²Fe^III(OTf) proved to be a good O₂ activator but a poor oxidation system, its association with another complex (TPEN)Fe^II(PF₆)₂ generates a complementary tandem couple for electro-assisted oxidation of substrates, working at a very accessible potential: upon reduction, L²Fe^III(OTf) activates O₂ to superoxide and transfers it to (TPEN)Fe^II(PF₆)₂ leading in fine to the oxidation of thioanisole.     

Evolution of Ate-Organoiron(II) Species towards Lower Oxidation States: Role of the Steric and Electronic Factors

Ate-iron(II) species such as [Ar₃Fe^II]⁻ (Ar=aryl) are key intermediates in Fe-catalyzed couplings between aryl nucleophiles and organic electrophiles. They can be active species in the catalytic cycle, or lead to Fe⁰ and Fe^I oxidation states, which can themselves be catalytically active or lead to unwished organic byproducts. Analysis of the reactivity of the intermediates obtained by step-by-step displacement of the mesityl groups in high-spin [Mes₃Fe^II]⁻ by less hindered phenyl ligands was performed, and uncovered the crucial role of both steric and electronic parameters in the formation of the Fe⁰ and Fe^I oxidation states. The formation of quaternized [Ar₄Fe^IIMgBr(THF)]⁻ intermediates allows the bielectronic reductive elimination energy required for the formation of Fe⁰ to be reduced. Similarly, the small steric pressure of the aryl groups in [Ar₃Fe^II]⁻ enables the formation of aryl-bridged [{Fe^II(Ar)₂}₂(μ-Ar)₂]²⁻ species, which afford the Fe^I oxidation state by bimetallic reductive elimination. These results are supported by ¹H NMR, EPR, and ⁵⁷Fe Mössbauer spectroscopies, as well as by DFT calculations.     

A Non‐Heme Iron Photocatalyst for Light‐Driven Aerobic Oxidation of Methanol

Non‐heme (L)Fe^III and (L)Fe^III‐O‐Fe^III(L) complexes (L=1,1‐di(pyridin‐2‐yl)‐N,N‐bis(pyridin‐2‐ylmethyl)ethan‐1‐amine) underwent reduction under irradiation to the Fe^II state with concomitant oxidation of methanol to methanal, without the need for a secondary photosensitizer. Spectroscopic and DFT studies support a mechanism in which irradiation results in charge‐transfer excitation of a Fe^III?μ‐O?Fe^III complex to generate [(L)Fe^IV=O]²⁺ (observed transiently during irradiation in acetonitrile), and an equivalent of (L)Fe^II. Under aerobic conditions, irradiation accelerates reoxidation from the Fe^II to the Fe^III state with O₂, thus closing the cycle of methanol oxidation to methanal.     

The FeII-FeIV and FeIII-FeV manifolds in an expanded world of Gif chemistry

The Gif systems for the selective functionalization of saturated hydrocarbons based on the reactions of Superoxide with Fe^II and of hydrogen peroxide with Fe^III are described. Both systems are relatively efficient, but not nearly so efficient as the electrochemical system developed in collaboration with Prof. G. Balavoine and Dr. Aurore Gref (Université de Paris-Sud-Orsay, France). All of the systems afford mainly ketones. This is an unusual selectivity, which implies a non-radical mechanism. It has been proven for the Fe^III-H₂O₂ system that the activation of the Fe^III is independent of the formation of ketone, which involves a hydroperoxide (derived from oxygen) as an intermediate. This intermediate controls the formation of ketone and of secondary alcohol. The addition of a number of trapping reagents such as BrCCl₃ diverts the reaction from oxygenation to bromide formation. Although BrCCl₃ is indeed a good trap for carbon radicals, the pattern of selectivity across a range of saturated hydrocarbons is completely different for Gif chemistry when compared with normal radical bromination. The chemistry is explained in terms of an Fe^V oxenoid species that inserts itself into secondary C-H bonds (a compromise between bond strength and steric hindrance). This gives an Fe^V intermediateA with an iron-carbon bond, which is probably rapidly reduced to the Fe^III state by hydrogen peroxide. Then oxygen is inserted into the Fe^III-C bond. Hydrolysis affords the isolateable intermediate hydroperoxide (intermediateB). A system based ontert-butyl hydroperoxide (TBHP) is described. This is similar to the above Gif systems, but the kinetic isotope effect is very different and the selectivity for adamantane substitution is different. However, Fe^III is activated by TBHP to an Fe^V oxenoid which, after reaction with a hydrocarbon, reacts with oxygen to give a hydroperoxide. So the pattern of intermediatesA andB is maintained with TBHP. Radical chemistry is involved in some of the reactions that involve ionic coupling to saturated hydrocarbons. The importance of the Fe^II-Fe^IV manifold in providing a mechanism that permits the selective functionalization of saturated hydrocarbons by ionic trapping with chloride, azide, and other anions is made manifest. Comparison is made with the Fe^III-Fe^V manifold where ionic trapping is never seen. Traditional Fenton chemistry (hydroxyl radical formation) is not operative here, but the trapping does involve the formation of carbon radicals. These react very efficiently with anions bonded to Fe^III.D. R. H. Barton is a Nobel Prize winner in chemistry in 1969. Since 1994, he is a foreign member of the Russian Academy of Sciences.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 595–604, April, 1995.We thank all our colleagues cited in the various References for their contributions to this fascinating subject. We also thank Prof. Minisci for his helpful comments. This work was supported by Quest Intl. and by the Welch Foundation.     

Comprehensive Evaluation of the Physicochemical Properties of LnIII Complexes of Aminoethyl‐DO3A as pH‐Responsive T1‐MRI Contrast Agents

N‐Substituted aminoethyl groups were attached to 1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid (DO3A) with the aim to design pH‐responsive Ln^III complexes based on the pH‐dependent on/off ligation of the amine nitrogen to the metal ion. The following ligands were synthesized: AE ‐ DO3A (aminoethyl‐DO3A), MAE ‐ DO3A (N‐methylaminoethyl‐DO3A), DMAE ‐ DO3A (N,N‐dimethylaminoethyl‐DO3A) and MEM ‐ AE ‐ DO3A (N‐methoxyethyl‐N‐methylaminoethyl‐DO3A). The physicochemical properties of the Ln^III complexes were investigated for the evaluation of their potential applicability as magnetic resonance imaging (MRI) contrast agents. In particular, a ¹H and ¹⁷O NMR relaxometric study was carried out for these Gd^III complexes at two different pH values: at basic pH (pendant amino group coordinated to the metal centre) and at acidic pH (protonated amine, not interacting with the metal ion). Eu^III complexes allow one to estimate the number of inner‐sphere water molecules through luminescence lifetime measurements and obtain some structural information through variable‐temperature (VT) high‐resolution ¹H NMR studies. Equilibria between differently hydrated species were found for most of the complexes at both acidic and basic pH. The thermodynamic stability of Ca^II, Zn^II, Cu^II and Ln^III complexes and kinetics of formation and dissociation reactions of Ln^III complexes of AE ‐ DO3A and DMAE ‐ DO3A were investigated showing stabilities comparable to currently approved Gd^III‐based CAs. In detail, higher total basicity (Σlog K_i^H) and higher stability constants of Ln^III complexes were found for AE ‐ DO3A with respect to DMAE ‐ DO3A (i.e., log K_{Gd‐ AE‐DO3A} =22.40 and log K_{Gd‐ DMAE‐DO3A} =20.56). The transmetallation reactions of Gd^III complexes are very slow (Gd‐ AE ‐ DO3A : t_1/2=2.7×10⁴ h; Gd‐ DMAE ‐ DO3A : 1.1×10⁵ h at pH 7.4 and 298 K) and occur through proton‐assisted dissociation.