Eckard Münck

An FeIV=O complex of a tetradentate tripodal nonheme ligand.

The reaction of [FeII(tris(2-pyridylmethyl)amine, TPA)(NCCH3)2]2+ with 1 equiv. peracetic acid in CH3CN at −40°C results in the nearly quantitative formation of a pale green intermediate with λmax at 724 nm (ɛ ≈ 300 M−1⋅cm−1) formulated as [FeIV(O)(TPA)]2+ by a combination of spectroscopic techniques. Its electrospray mass spectrum shows a prominent feature at m/z 461, corresponding to the [FeIV(O)(TPA)(ClO4)]+ ion. The Mössbauer spectra recorded in zero field reveal a doublet with ΔEQ = 0.92(2) mm/s and δ = 0.01(2) mm/s; analysis of spectra obtained in strong magnetic fields yields parameters characteristic of S = 1 FeIVO complexes. The presence of an FeIVO unit is also indicated in its Fe K-edge x-ray absorption spectrum by an intense 1-s → 3-d transition and the requirement for an O/N scatterer at 1.67 Å to fit the extended x-ray absorption fine structure region. The [FeIV(O)(TPA)]2+ intermediate is stable at −40°C for several days but decays quantitatively on warming to [Fe2(μ-O)(μ-OAc)(TPA)2]3+. Addition of thioanisole or cyclooctene at −40°C results in the formation of thioanisole oxide (100% yield) or cyclooctene oxide (30% yield), respectively; thus [FeIV(O)(TPA)]2+ is an effective oxygen-atom transfer agent. It is proposed that the FeIVO species derives from O—O bond heterolysis of an unobserved FeII(TPA)-acyl peroxide complex. The characterization of [FeIV(O)(TPA)]2+ as having a reactive terminal FeIVO unit in a nonheme ligand environment lends credence to the proposed participation of analogous species in the oxygen activation mechanisms of many mononuclear nonheme iron enzymes.

A Synthetic High‐Spin Oxoiron(IV) Complex: Generation, Spectroscopic Characterization, and Reactivity

High versus low: The high-yield generation of a synthetic high-spin oxoiron(IV) complex, [Fe(IV)(O)(TMG(3)tren)](2+) (see picture, TMG(3)tren = 1,1,1-tris{2-[N2-(1,1,3,3-tetramethylguanidino)]ethyl}amine), has been achieved by using the very bulky tetradentate TMG(3)tren ligand, in order to both sterically protect the oxoiron(IV) moiety and enforce a trigonal bipyramidal geometry at the iron center, for which an S = 2 ground state is favored.

A thiolate-ligated nonheme oxoiron(IV) complex relevant to cytochrome P450.

Thiolate-ligated oxoiron(IV) centers are postulated to be the key oxidants in the catalytic cycles of oxygen-activating cytochrome P450 and related enzymes. Despite considerable synthetic efforts, chemists have not succeeded in preparing an appropriate model complex. Here we report the synthesis and spectroscopic characterization of [FeIV(O)(TMCS)]+ where TMCS is a pentadentate ligand that provides a square pyramidal N4(SR)apical, where SR is thiolate, ligand environment about the iron center, which is similar to that of cytochrome P450. The rigidity of the ligand framework stabilizes the thiolate in an oxidizing environment. Reactivity studies suggest that thiolate coordination favors hydrogen-atom abstraction chemistry over oxygen-atom transfer pathways in the presence of reducing substrates.

AN FEIVO COMPLEX COMPLEX OF A TETRADENTATE TRIPODAL NONHEME LIGAND

The reaction of [FeII(tris(2-pyridylmethyl)amine, TPA)(NCCH3)2]2+ with 1 equiv. peracetic acid in CH3CN at −40°C results in the nearly quantitative formation of a pale green intermediate with λmax at 724 nm (ɛ ≈ 300 M−1⋅cm−1) formulated as [FeIV(O)(TPA)]2+ by a combination of spectroscopic techniques. Its electrospray mass spectrum shows a prominent feature at m/z 461, corresponding to the [FeIV(O)(TPA)(ClO4)]+ ion. The Mössbauer spectra recorded in zero field reveal a doublet with ΔEQ = 0.92(2) mm/s and δ = 0.01(2) mm/s; analysis of spectra obtained in strong magnetic fields yields parameters characteristic of S = 1 FeIVO complexes. The presence of an FeIVO unit is also indicated in its Fe K-edge x-ray absorption spectrum by an intense 1-s → 3-d transition and the requirement for an O/N scatterer at 1.67 Å to fit the extended x-ray absorption fine structure region. The [FeIV(O)(TPA)]2+ intermediate is stable at −40°C for several days but decays quantitatively on warming to [Fe2(μ-O)(μ-OAc)(TPA)2]3+. Addition of thioanisole or cyclooctene at −40°C results in the formation of thioanisole oxide (100% yield) or cyclooctene oxide (30% yield), respectively; thus [FeIV(O)(TPA)]2+ is an effective oxygen-atom transfer agent. It is proposed that the FeIVO species derives from O—O bond heterolysis of an unobserved FeII(TPA)-acyl peroxide complex. The characterization of [FeIV(O)(TPA)]2+ as having a reactive terminal FeIVO unit in a nonheme ligand environment lends credence to the proposed participation of analogous species in the oxygen activation mechanisms of many mononuclear nonheme iron enzymes.

Million-fold activation of the [Fe2(μ-O)2] diamond core for C-H bond cleavage

In biological systems, the cleavage of strong C–H bonds is often carried out by iron centers – such as the methane monooxygenase in methane hydroxylation – through dioxygen activation mechanisms. High valent species with [Fe2(μ-O)2] diamond cores are thought to act as the oxidizing moieties, but the synthesis of complexes that cleave strong C–H bonds efficiently has remained a challenge. We report here the conversion of a synthetic complex with a valence-delocalized [Fe3.5(μ-O)2Fe3.5]3+ diamond core (1) into a complex with a valence-localized [HO-FeIII-O-FeIV=O]2+ open core (4), which cleaves C–H bonds over million-fold faster. This activity enhancement results from three factors: the formation of a terminal oxoiron(IV) moiety, the conversion of the low-spin (S = 1) FeIV=O center to a high-spin (S = 2) center, and the concentration of the oxidizing capability to the active terminal oxoiron(IV) moiety. This suggests that similar isomerization strategies might be employed by nonheme diiron enzymes.

The Crystal Structure of a High-Spin OxoIron(IV) Complex and Characterization of Its Self-Decay Pathway

[Fe(IV)(O)(TMG(3)tren)](2+) (1; TMG(3)tren = 1,1,1-tris{2-[N(2)-(1,1,3,3-tetramethylguanidino)]ethyl}amine) is a unique example of an isolable synthetic S = 2 oxoiron(IV) complex, which serves as a model for the high-valent oxoiron(IV) intermediates observed in nonheme iron enzymes. Congruent with DFT calculations predicting a more reactive S = 2 oxoiron(IV) center, 1 has a lifetime significantly shorter than those of related S = 1 oxoiron(IV) complexes. The self-decay of 1 exhibits strictly first-order kinetic behavior and is unaffected by solvent deuteration, suggesting an intramolecular process. This hypothesis was supported by ESI-MS analysis of the iron products and a significant retardation of self-decay upon use of a perdeuteromethyl TMG(3)tren isotopomer, d(36)-1 (KIE = 24 at 25 degrees C). The greatly enhanced thermal stability of d(36)-1 allowed growth of diffraction quality crystals for which a high-resolution crystal structure was obtained. This structure showed an Fe horizontal lineO unit (r = 1.661(2) A) in the intended trigonal bipyramidal geometry enforced by the sterically bulky tetramethylguanidinyl donors of the tetradentate tripodal TMG(3)tren ligand. The close proximity of the methyl substituents to the oxoiron unit yielded three symmetrically oriented short C-D...O nonbonded contacts (2.38-2.49 A), an arrangement that facilitated self-decay by rate-determining intramolecular hydrogen atom abstraction and subsequent formation of a ligand-hydroxylated iron(III) product. EPR and Mossbauer quantification of the various iron products, referenced against those obtained from reaction of 1 with 1,4-cyclohexadiene, allowed formulation of a detailed mechanism for the self-decay process. The solution of this first crystal structure of a high-spin (S = 2) oxoiron(IV) center represents a fundamental step on the path toward a full understanding of these pivotal biological intermediates.

Proton- and Reductant-Assisted Dioxygen Activation by a Nonheme Iron(II) Complex to Form an Oxoiron(IV) Intermediate

Dioxygen activation by mononuclear iron oxygenases in general requires two electrons and protons to facilitate the reductive cleavage of the O-O bond and formation of a high-valent iron oxidant.[1,2] For enzymes with an iron(III) resting state, the oxidant is postulated to have a formally FeV oxidation state, e.g. FeIV(O)(porphyrin radical) for cytochrome P450[i] and FeV(O)(OH) for the Rieske dioxygenases.[ii] On the other hand, enzymes with an iron(II) resting state often require a tetrahydropterin or an α-keto acid cofactor to form an FeIV(O) intermediate.[2] Such intermediates have recently been trapped and characterized for several enzymes.[iii]

Axial Ligand Effects on the Geometric and Electronic Structures of Nonheme Oxoiron(IV) Complexes

A series of complexes [Fe(IV)(O)(TMC)(X)](+) (where X = OH(-), CF3CO2(-), N3(-), NCS(-), NCO(-), and CN(-)) were obtained by treatment of the well-characterized nonheme oxoiron(IV) complex [Fe(IV)(O)(TMC)(NCMe)](2+) (TMC = tetramethylcyclam) with the appropriate NR4X salts. Because of the topology of the TMC macrocycle, the [Fe(IV)(O)(TMC)(X)](+) series represents an extensive collection of S = 1 oxoiron(IV) complexes that only differ with respect to the ligand trans to the oxo unit. Electronic absorption, Fe K-edge X-ray absorption, resonance Raman, and Mossbauer data collected for these complexes conclusively demonstrate that the characteristic spectroscopic features of the S = 1 Fe(IV)=O unit, namely, (i) the near-IR absorption properties, (ii) X-ray absorption pre-edge intensities, and (iii) quadrupole splitting parameters, are strongly dependent on the identity of the trans ligand. However, on the basis of extended X-ray absorption fine structure data, most [Fe(IV)(O)(TMC)(X)](+) species have Fe=O bond lengths similar to that of [Fe(IV)(O)(TMC)(NCMe)](2+) (1.66 +/- 0.02 A). The mechanisms by which the trans ligands perturb the Fe(IV)=O unit were probed using density functional theory (DFT) computations, yielding geometric and electronic structures in good agreement with our experimental data. These calculations revealed that the trans ligands modulate the energies of the Fe=O sigma- and pi-antibonding molecular orbitals, causing the observed spectroscopic changes. Time-dependent DFT methods were used to aid in the assignment of the intense near-UV absorption bands found for the oxoiron(IV) complexes with trans N3(-), NCS(-), and NCO(-) ligands as X(-)-to-Fe(IV)=O charge-transfer transitions, thereby rationalizing the resonance enhancement of the nu(Fe=O) mode upon excitation of these chromophores.

Trapping and spectroscopic characterization of an FeIII-superoxo intermediate from a nonheme mononuclear iron-containing enzyme

intermediates are well known in heme enzymes, but none have been characterized in the nonheme mononuclear FeII enzyme family. Many steps in the O2 activation and reaction cycle of FeII-containing homoprotocatechuate 2,3-dioxygenase are made detectable by using the alternative substrate 4-nitrocatechol (4NC) and mutation of the active site His200 to Asn (H200N). Here, the first intermediate (Int-1) observed after adding O2 to the H200N-4NC complex is trapped and characterized using EPR and Mössbauer (MB) spectroscopies. Int-1 is a high-spin (S1 = 5/2) FeIII antiferromagnetically (AF) coupled to an S2 = 1/2 radical (J ≈ 6 cm-1 in ). It exhibits parallel-mode EPR signals at g = 8.17 from the S = 2 multiplet, and g = 8.8 and 11.6 from the S = 3 multiplet. These signals are broadened significantly by hyperfine interactions (A17O ≈ 180 MHz). Thus, Int-1 is an AF-coupled species. The experimental observations are supported by density functional theory calculations that show nearly complete transfer of spin density to the bound O2. Int-1 decays to form a second intermediate (Int-2). MB spectra show that it is also an AF-coupled FeIII-radical complex. Int-2 exhibits an EPR signal at g = 8.05 arising from an S = 2 state. The signal is only slightly broadened by (< 3% spin delocalization), suggesting that Int-2 is a peroxo-FeIII-4NC semiquinone radical species. Our results demonstrate facile electron transfer between FeII, O2, and the organic ligand, thereby supporting the proposed wild-type enzyme mechanism.

A synthetic precedent for the [FeIV2(μ-O)2] diamond core proposed for methane monooxygenase intermediate Q

Intermediate Q, the methane-oxidizing species of soluble methane monooxygenase, is proposed to have an [FeIV2(μ-O)2] diamond core. In an effort to obtain a synthetic precedent for such a core, bulk electrolysis at 900 mV (versus Fc+/0) has been performed in MeCN at −40°C on a valence-delocalized [FeIIIFeIV(μ-O)2(Lb)2]3+ complex (1b) (E1/2 = 760 mV versus Fc+/0). Oxidation of 1b results in the near-quantitative formation of a deep red complex, designated 2b, that exhibits a visible spectrum with λmax at 485 nm (9,800 M−1·cm−1) and 875 nm (2,200 M−1·cm−1). The 4.2 K Mössbauer spectrum of 2b exhibits a quadrupole doublet with δ = −0.04(1) mm·s−1 and ΔEQ = 2.09(2) mm·s−1, parameters typical of an iron(IV) center. The Mössbauer patterns observed in strong applied fields show that 2b is an antiferromagnetically coupled diiron(IV) center. Resonance Raman studies reveal the diagnostic vibration mode of the [Fe2(μ-O)2] core at 674 cm−1, downshifting 30 cm−1 upon 18O labeling. Extended x-ray absorption fine structure (EXAFS) analysis shows two O/N scatterers at 1.78 Å and an Fe scatterer at 2.73 Å. Based on the accumulated spectroscopic evidence, 2b thus can be formulated as [FeIV2(μ-O)2(Lb)2]4+, the first synthetic complex with an [FeIV2(μ-O)2] core. A comparison of 2b and its mononuclear analog [FeIV(O)(Lb)(NCMe)]2+ (4b) reveals that 4b is 100-fold more reactive than 2b in oxidizing weak CH bonds. This surprising observation may shed further light on how intermediate Q carries out the hydroxylation of methane.