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.

Prognostic significance of perihematomal edema in basal ganglia hemorrhage after minimally invasive endoscopic evacuation.

Objective: Spontaneous basal ganglia hemorrhage is a common type of intracerebral hemorrhage (ICH) with no definitive treatment. Minimally invasive endoscopic evacuation is a promising therapeutic approach for ICH. In this study the authors examined prognostic factors associated with long-term functional dependence (modified Rankin Scale [mRS] score ≥ 4) in patients who had undergone endoscopic evacuation of basal ganglia hemorrhage.

Long-term outcome of stereotactic aspiration, endoscopic evacuation, and open craniotomy for the treatment of spontaneous basal ganglia hemorrhage: a propensity score study of 703 cases.

Background: To compare the long-term therapeutic effects of stereotactic aspiration (SA), endoscopic evacuation (EE), and open craniotomy (OC) in the surgical treatment of spontaneous basal ganglia hemorrhage and explore the appropriate clinical indications for each technique.

Methods: Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to evaluate the therapeutic effects of these techniques. The primary and secondary outcomes were 6-month modified Rankin Scale (mRS) and mortality rates, respectively.

Stepwise nitrosylation of the nonheme iron site in an engineered azurin and a molecular basis for nitric oxide signaling mediated by nonheme iron proteins.

Mononitrosyl and dinitrosyl iron species, such as {FeNO}, {FeNO} and {Fe(NO)}, have been proposed to play pivotal roles in the nitrosylation processes of nonheme iron centers in biological systems. Despite their importance, it has been difficult to capture and characterize them in the same scaffold of either native enzymes or their synthetic analogs due to the distinct structural requirements of the three species, using redox reagents compatible with biomolecules under physiological conditions. Here, we report the realization of stepwise nitrosylation of a mononuclear nonheme iron site in an engineered azurin under such conditions.

Long-Term Effect of Endoscopic Evacuation for Large Basal Ganglia Hemorrhage With GCS Scores ≦ 8.

The surgical evacuation, including stereotactic aspiration, endoscopic evacuation, and craniotomy, is the most effective way to reduce the volume of intracerebral hemorrhage. However, credible evidence for the effects of these techniques is still insufficient. The present study explored the long-term outcomes of these techniques in the treatment of basal ganglia hematoma with low Glasgow Coma Scale (GCS) scores (≤8) and large-volume (≥40 ml), which were predictors of high mortality.

Comparison of Long-Term Outcomes of Endoscopic and Minimally Invasive Catheter Evacuation for the Treatment of Spontaneous Cerebellar Hemorrhage.

Recently, minimally invasive techniques, including endoscopic evacuation and minimally invasive catheter (MIC) evacuation, have been used for the treatment of patients with spontaneous cerebellar hemorrhage (SCH). However, credible evidence is still needed to validate the effects of these techniques. To explore the long-term outcomes of both surgical techniques in the treatment of SCH.

Effects of Noncovalent Interactions on High-Spin Fe(IV)-Oxido Complexes.

High-valent nonheme Fe-oxido species are key intermediates in biological oxidation, and their properties are proposed to be influenced by the unique microenvironments present in protein active sites. Microenvironments are regulated by noncovalent interactions, such as hydrogen bonds (H-bonds) and electrostatic interactions; however, there is little quantitative information about how these interactions affect crucial properties of high valent metal-oxido complexes. To address this knowledge gap, we introduced a series of Fe-oxido complexes that have the same S = 2 spin ground state as those found in nature and then systematically probed the effects of noncovalent interactions on their electronic, structural, and vibrational properties.

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.

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)] ().

Spectroscopic Description of the E State of Mo Nitrogenase Based on Mo and Fe X-ray Absorption and Mössbauer Studies.

Mo nitrogenase (N2ase) utilizes a two-component protein system, the catalytic MoFe and its electron-transfer partner FeP, to reduce atmospheric dinitrogen (N) to ammonia (NH). The FeMo cofactor contained in the MoFe protein serves as the catalytic center for this reaction and has long inspired model chemistry oriented toward activating N. This field of chemistry has relied heavily on the detailed characterization of how Mo N2ase accomplishes this feat.

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.

Oxidative Decarboxylase UndA Utilizes a Dinuclear Iron Cofactor.

UndA is a nonheme iron enzyme that activates oxygen to catalyze the decarboxylation of dodecanoic acid to undecene and carbon dioxide. We report the first optical and Mössbauer spectroscopic characterization of UndA, revealing that the enzyme harbors a coupled dinuclear iron cluster. Single turnover studies confirm that the reaction of the diferrous enzyme with dioxygen produces stoichiometric product per cluster.

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.

Repurposing Nonheme Iron Hydroxylases To Enable Catalytic Nitrile Installation through an Azido Group Assistance.

Three mononuclear nonheme iron and 2-oxoglutarate dependent enzymes, l-Ile 4-hydroxylase, l-Leu 5-hydroxylase and polyoxin dihydroxylase, are previously reported to catalyze the hydroxylation of l-isoleucine, l-leucine, and l-α-amino-δ-carbamoylhydroxyvaleric acid (ACV). In this study, we showed that these enzymes can accommodate leucine isomers and catalyze regiospecific hydroxylation. On the basis of these results, as a proof-of-concept, we demonstrated that the outcome of the reaction can be redirected by installation of an assisting group within the substrate.

Crystallographic Evidence for a Sterically Induced Ferryl Tilt in a Non-Heme Oxoiron(IV) Complex that Makes it a Better Oxidant.

Oxoiron(IV) units are often implicated as intermediates in the catalytic cycles of non-heme iron oxygenases and oxidases. The most reactive synthetic analogues of these intermediates are supported by tetradentate tripodal ligands with N-methylbenzimidazole or quinoline donors, but their instability precludes structural characterization. Herein we report crystal structures of two [Fe (O)(L)] complexes supported by pentadentate ligands incorporating these heterocycles, which show longer average Fe-N distances than the complex with only pyridine donors.

Spectroscopic and DFT Characterization of a Highly Reactive Nonheme Fe-Oxo Intermediate.

The reaction of [(PyNMe)Fe(CFSO)], 1, with excess peracetic acid at -40 °C generates a highly reactive intermediate, 2b(PAA), that has the fastest rate to date for oxidizing cyclohexane by a nonheme iron species. It exhibits an intense 490 nm chromophore associated with an S = 1/2 EPR signal having g-values at 2.07, 2.

Characterization of the Fleeting Hydroxoiron(III) Complex of the Pentadentate TMC-py Ligand.

Nonheme mononuclear hydroxoiron(III) species are important intermediates in biological oxidations, but well-characterized examples of synthetic complexes are scarce due to their instability or tendency to form μ-oxodiiron(III) complexes, which are the thermodynamic sink for such chemistry. Herein, we report the successful stabilization and characterization of a mononuclear hydroxoiron(III) complex, [Fe(OH)(TMC-py)] (3; TMC-py = 1-(pyridyl-2'-methyl)-4,8,11-trimethyl-1,4,8,11-tetrazacyclotetradecane), which is directly generated from the reaction of [Fe(O)(TMC-py)] (2) with 1,4-cyclohexadiene at -40 °C by H-atom abstraction. Complex 3 exhibits a UV spectrum with a λ at 335 nm (ε ≈ 3500 M cm) and a molecular ion in its electrospray ionization mass spectrum at m/z 555 with an isotope distribution pattern consistent with its formulation.

CmlI N-Oxygenase Catalyzes the Final Three Steps in Chloramphenicol Biosynthesis without Dissociation of Intermediates.

CmlI catalyzes the six-electron oxidation of an aryl-amine precursor (NH-CAM) to the aryl-nitro group of chloramphenicol (CAM). The active site of CmlI contains a (hydr)oxo- and carboxylate-bridged dinuclear iron cluster. During catalysis, a novel diferric-peroxo intermediate P is formed and is thought to directly effect oxygenase chemistry.

The Two Faces of Tetramethylcyclam in Iron Chemistry: Distinct Fe-O-M Complexes Derived from [Fe(O)(TMC)] Isomers.

Tetramethylcyclam (TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) exhibits two faces in supporting an oxoiron(IV) moiety, as exemplified by the prototypical [(TMC)Fe(O)(NCCH)](OTf), where anti indicates that the O atom is located on the face opposite all four methyl groups, and the recently reported syn isomer [(TMC)Fe(O)(OTf)](OTf). The ability to access two isomers of [(TMC)Fe(O)] raises the fundamental question of how ligand topology can affect the properties of the metal center. Previously, we have reported the formation of [(CHCN)(TMC)Fe-O-Cr(OTf)(NCCH)] (1) by inner-sphere electron transfer between Cr(OTf) and [(TMC)Fe(O)(NCCH)](OTf).

Mechanism for Six-Electron Aryl-N-Oxygenation by the Non-Heme Diiron Enzyme CmlI.

The ultimate step in chloramphenicol (CAM) biosynthesis is a six-electron oxidation of an aryl-amine precursor (NH2-CAM) to the aryl-nitro group of CAM catalyzed by the non-heme diiron cluster-containing oxygenase CmlI. Upon exposure of the diferrous cluster to O2, CmlI forms a long-lived peroxo intermediate, P, which reacts with NH2-CAM to form CAM. Since P is capable of at most a two-electron oxidation, the overall reaction must occur in several steps.

Modeling Non-Heme Iron Halogenases: High-Spin Oxoiron(IV)-Halide Complexes That Halogenate C-H Bonds.

The non-heme iron halogenases CytC3 and SyrB2 catalyze C-H bond halogenation in the biosynthesis of some natural products via S = 2 oxoiron(IV)-halide intermediates. These oxidants abstract a hydrogen atom from a substrate C-H bond to generate an alkyl radical that reacts with the bound halide to form a C-X bond chemoselectively. The origin of this selectivity has been explored in biological systems but has not yet been investigated with synthetic models.