Nonheme Mononuclear and Dinuclear Iron(II) and Iron(III) Fluoride Complexes and Their Fluorine Radical Transfer Reactivity.

The nonheme iron(II) complexes containing a fluoride anion, Fe(BNPAO)(F) () and [Fe(BNPAOH)(F)(THF)](BF) (), were synthesized and structurally characterized. Addition of dioxygen to either or led to the formation of a fluoride-bridged, dinuclear iron(III) complex [Fe(BNPAO)(F)(μ-F)] (), which was characterized by single-crystal X-ray diffraction, H NMR, and elemental analysis. An iron(II)(iodide) complex, Fe(BNPAO)(I) (), was prepared and reacted with O to give the mononuclear complex -Fe(BNPAO)(OH)(I) ().

Influence of the second coordination sphere on O activation by a nonheme iron(II) thiolate complex.

The synthesis and characterization of a new ligand, 1-(bis(pyridin-2-ylmethyl) amino)-2-methylpropane-2-thiolate (BPAS) and its nonheme iron complex, Fe(BPAS)Br (1), is reported. Reaction of 1 with O at -20 °C generates a high-spin iron(III)-hydroxide complex, [Fe(OH)(BPAS)(Br)] (2), that was characterized by UV-vis, Fe Mössbauer, and electron paramagnetic resonance (EPR) spectroscopies, and electrospray ionization mass spectrometry (ESI-MS). Density functional theory (DFT) calculations were employed to support the spectroscopic assignments.

Factors controlling the reactivity of synthetic compound-I Analogs.

A high-valent iron(IV)-oxo porphyrin radical cation (Fe(O)(porph) serves as a key, reactive intermediate for a range of heme enzymes, including cytochrome P450 (CYP), horseradish peroxidase (HRP), and catalase (CAT). Synthetic analogs of this intermediate, known as Compound-I (Cpd-I) in the heme enzyme literature, have been generated with different tetrapyrrolic, macrocyclic ligands, including porphyrin derivatives, and the closely related ring-contracted macrocycles, corroles and corrolazines. These synthetic analogs have been useful for assigning and understanding structural and spectroscopic features and examining the reactivity of Cpd-I-like species in controlled and well-defined environments.

Chemoselective Proteomics, Zinc Fingers, and a Zinc(II) Model for HS Mediated Persulfidation.

The gasotransmitter hydrogen sulfide (HS) is thought to be involved in the post-translational modification of cysteine residues to produce reactive persulfides. A persulfide-specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by Zn, O, and HS, with intermediates involving oxygen- and sulfur-based radicals detected by mass spectrometry and optical spectroscopies.

Axial Ligation Impedes Proton-Coupled Electron-Transfer Reactivity of a Synthetic Compound-I Analogue.

The nature of the axial ligand in high-valent iron-oxo heme enzyme intermediates and related synthetic catalysts is a critical structural element for controlling proton-coupled electron-transfer (PCET) reactivity of these species. Herein, we describe the generation and characterization of three new 6-coordinate, iron(IV)-oxo porphyrinoid-π-cation-radical complexes and report their PCET reactivity together with a previously published 5-coordinate analogue, Fe(O)(TBPCz) (TBPCz = octakis(--butylphenyl)corrolazinato) () (Cho, K. A high-valent iron-oxo corrolazine activates C-H bonds via hydrogen-atom transfer.

A Nonheme Iron(III) Superoxide Complex Leads to Sulfur Oxygenation.

A new alkylthiolate-ligated nonheme iron complex, Fe(BNPAS)Br (), is reported. Reaction of with O at -40 °C, or reaction of the ferric form with O at -80 °C, gives a rare iron(III)-superoxide intermediate, [Fe(O)(BNPAS)] (), characterized by UV-vis, Fe Mössbauer, ATR-FTIR, EPR, and CSIMS. Metastable then converts to an S-oxygenated Fe(sulfinate) product via a sequential O atom transfer mechanism involving an iron-sulfenate intermediate.

Selective Radical Transfer in a Series of Nonheme Iron(III) Complexes.

A series of nonheme iron complexes, Fe(BNPAO)(L)(L) (L = N, NCS, NCO, and Cl) have been synthesized using the previously reported BNPAO ligand. The ferrous analogs Fe(BNPAO)(L) (L = N, NCS, and NCO) were also prepared. The complexes were structurally characterized using single crystal X-ray diffraction, which shows that all the Fe complexes are six-coordinate, with one anionic ligand (L) in the H-bonding axial site and the other anionic ligand (L) in the equatorial plane, cis to the L ligand.

Investigating Metal-Metal Bond Polarization in a Heteroleptic Tris-Ylide Diiron System.

This article describes the synthesis, characterization, and S-atom transfer reactivity of a series of -symmetric diiron complexes. The iron centers in each complex are coordinated in distinct ligand environments, with one (Fe) bound in a pseudo-trigonal bipyramidal geometry by three phosphinimine nitrogens in the equatorial plane, a tertiary amine, and the second metal center (Fe). Fe is coordinated, in turn, by Fe, three ylidic carbons in a trigonal plane, and, in certain cases, by an axial oxygen donor.

Oxygen versus Sulfur Coordination in Cobalt Superoxo Complexes: Spectroscopic Properties, O Binding, and H-Atom Abstraction Reactivity.

A five-coordinate, disiloxide-ligated cobalt(II) ( = 3/2) complex () was prepared as an oxygen-ligated analogue to the previously reported silanedithiolate-ligated Co(MeTACN)(SSiMe) ( , , 3641-3653). The structural and spectroscopic properties of were analyzed by single-crystal X-ray diffraction, electron paramagnetic resonance (EPR), and NMR spectroscopies. The reactivity of with dioxygen was examined, and it was shown to bind O reversibly in a range of solvents at low temperatures.

Nonheme Iron(III) Azide and Iron(III) Isothiocyanate Complexes: Radical Rebound Reactivity, Selectivity, and Catalysis.

The new nonheme iron complexes Fe(BNPAO)(N) (), Fe(BNPAO)(OH)(N) (), Fe(BNPAO)(OH) (), Fe(BNPAO)(OH)(NCS) (), Fe(BNPAO)(NCS) (), Fe(BNPAO)(NCS) (), and Fe(BNPAO)(N) () (BNPAO = 2-(bis((6-(neopentylamino)pyridin-2-yl) methyl)amino)-1,1-diphenylethanolate) were synthesized and characterized by single crystal X-ray diffraction (XRD), as well as by H NMR, Fe Mössbauer, and ATR-IR spectroscopies. Complex was reacted with a series of carbon radicals, ArC· (Ar = -X-CH), analogous to the proposed radical rebound step for nonheme iron hydroxylases and halogenases. The results show that for ArC· (X = Cl, H, Bu), only OH· transfer occurs to give ArCOH.

Iron Insertion at the Assembly Site of the ISCU Scaffold Protein Is a Conserved Process Initiating Fe-S Cluster Biosynthesis.

Iron-sulfur (Fe-S) clusters are prosthetic groups of proteins biosynthesized on scaffold proteins by highly conserved multi-protein machineries. Biosynthesis of Fe-S clusters into the ISCU scaffold protein is initiated by ferrous iron insertion, followed by sulfur acquisition, via a still elusive mechanism. Notably, whether iron initially binds to the ISCU cysteine-rich assembly site or to a cysteine-less auxiliary site via N/O ligands remains unclear.

Direct Reduction of NO to NO by a Mononuclear Nonheme Thiolate Ligated Iron(II) Complex via Formation of a Metastable {FeNO} Complex.

Addition of NO to a nonheme dithiolate-ligated iron(II) complex, Fe(MeTACN)(SSiMe) (), results in the generation of NO. Low-temperature spectroscopic studies reveal a metastable six-coordinate {FeNO} intermediate ( = 3/2) that was trapped at -135 °C and was characterized by low-temperature UV-vis, resonance Raman, EPR, Mössbauer, XAS, and DFT studies. Thermal decay of the {FeNO} species leads to the evolution of NO, providing a rare example of a mononuclear thiolate-ligated {FeNO} that mediates NO reduction to NO without the requirement of any exogenous electron or proton sources.

What Drives Radical Halogenation versus Hydroxylation in Mononuclear Nonheme Iron Complexes? A Combined Experimental and Computational Study.

Nonheme iron halogenases are unique enzymes in nature that selectively activate an aliphatic C-H bond of a substrate to convert it into C-X (X = Cl/Br, but not F/I). It is proposed that they generate an Fe(OH)(X) intermediate in their catalytic cycle. The analogous Fe(OH) intermediate in nonheme iron hydroxylases transfers OH to give alcohol product, whereas the halogenases transfer X to the carbon radical substrate.

A Reactive, Photogenerated High-Spin ( = 2) Fe(O) Complex via O Activation.

Addition of dioxygen at low temperature to the non-heme ferrous complex Fe(MeTACN)((OSi)O) () in 2-MeTHF produces a peroxo-bridged diferric complex Fe(μ-O)(MeTACN)((OSi)O) (), which was characterized by UV-vis, resonance Raman, and variable field Mössbauer spectroscopies. Illumination of a frozen solution of in THF with white light leads to homolytic O-O bond cleavage and generation of a Fe(O) complex (ν(Fe=O) = 818 cm; δ = 0.22 mm s, Δ = 0.

Halogen Transfer to Carbon Radicals by High-Valent Iron Chloride and Iron Fluoride Corroles.

High-valent iron halide corroles were examined to determine their reactivity with carbon radicals and their ability to undergo radical rebound-like processes. Beginning with Fe(Cl)(ttppc) () (ttppc = 5,10,15-tris(2,4,6-triphenylphenyl)corrolato), the new iron corroles Fe(OTf)(ttppc) (), Fe(OTf)(ttppc)(AgOTf) (), and Fe(F)(ttppc) () were synthesized. Complexes and are the first iron triflate and iron fluoride corroles to be structurally characterized by single crystal X-ray diffraction.

A Nonheme Mononuclear {FeNO} Complex that Produces N O in the Absence of an Exogenous Reductant.

A new nonheme iron(II) complex, Fe (Me TACN)((OSi ) O) (1), is reported. Reaction of 1 with NO gives a stable mononitrosyl complex Fe(NO)(Me TACN)((OSi ) O) (2), which was characterized by Mössbauer (δ=0.52 mm s , |ΔE |=0.

Evaluation of the Physicochemical Properties of the Iron Nanoparticle Drug Products: Brand and Generic Sodium Ferric Gluconate.

Complex iron nanoparticle-based drugs are one of the oldest and most frequently administered classes of nanomedicines. In the US, there are seven FDA-approved iron nanoparticle reference drug products, of which one also has an approved generic drug product (i.e.

The Selective Monobromination of a Highly Sterically Encumbered Corrole: Structural and Spectroscopic Properties of Fe(Cl)(2-Bromo-5,10,15-tris(triphenyl)phenyl corrole).

The corrole ligand serves as a versatile tri-anionic, macrocyclic platform on which to model biological catalytic systems, as well as to effect mechanistically challenging chemical transformations. Here in we describe the synthesis, structure, and characterization of an isomerically pure corrole ligand, selectively mono-brominated at the β-carbon position adjacent to the corrole C-C bond (2-C) and produced in relatively high yields, as well as its iron chloride complex. Analysis of the iron metalated complex by cyclic voltammetry shows that the bromine being present on the ligand resulted in anodic shifts of +93 and +63 mV for first oxidation and first reduction of the complex respectively.

Temperature-Dependent Reactivity of a Non-heme Fe(OH)(SR) Complex: Relevance to Isopenicillin N Synthase.

Non-heme iron complexes with -Fe(OH)(SAr/OAr) coordination were isolated and examined for their reactivity with a tertiary carbon radical. The sulfur-ligated complex shows a temperature dependence on OH versus ArS transfer, whereas the oxygen-ligated complex does not. These results provide the first working model for C-S bond formation in isopenicillin N synthase and indicate that kinetic control may be a key factor in the selectivity of non-heme iron "rebound" processes.

Hydroxyl Transfer to Carbon Radicals by Mn(OH) vs Fe(OH) Corrole Complexes.

The transfer of •OH from metal-hydroxo species to carbon radicals (R•) to give hydroxylated products (ROH) is a fundamental process in metal-mediated heme and nonheme C-H bond oxidations. This step, often referred to as the hydroxyl "rebound" step, is typically very fast, making direct study of this process challenging if not impossible. In this report, we describe the reactions of the synthetic models M(OH)(ttppc) (M = Fe (), Mn (); ttppc = 5,10,15-tris(2,4,6-triphenyl)phenyl corrolato) with a series of triphenylmethyl carbon radical (R•) derivatives ((4-X-CH)C•; X = OMe, tBu, Ph, Cl, CN) to give the one-electron reduced M(ttppc) complexes and ROH products.

Determining the Inherent Selectivity for Carbon Radical Hydroxylation versus Halogenation with Fe(OH)(X) Complexes: Relevance to the Rebound Step in Non-heme Iron Halogenases.

The first structural models of the proposed -Fe(OH)(halide) intermediate in the non-heme iron halogenases were synthesized and examined for their inherent reactivity with tertiary carbon radicals. Selective hydroxylation occurs for these -Fe(OH)(X) (X = Cl, Br) complexes in a radical rebound-like process. In contrast, a -Fe(Cl) complex reacts with carbon radicals to give halogenation.

Oxidation of an indole substrate by porphyrin iron(iii) superoxide: relevance to indoleamine and tryptophan 2,3-dioxygenases.

Reaction of FeIII(O2˙-)(TPP) with 2,3-dimethylindole at -40 °C gives the ring-opened, dioxygenated N-(2-acetyl-phenyl)-acetamide product. The reaction was monitored in situ by low-temperature UV-vis and 1H NMR spectroscopies. This work demonstrates that a discrete iron(iii)(superoxo) porphyrin is competent to carry out indole oxidation, as proposed for the tryptophan and indoleamine 2,3-dioxygenases.