Non-heme Iron Complexes Research Articles

Highly efficient asymmetric aerobic oxidative coupling of 2-naphthols in the presence of bioinspired iron aminopyridine complexes

For the first time, it has been shown that chiral bipyrrolidine derived bioinspired non-heme iron complexes of the types [LFeX2], [LFe(μ-O)2FeL][X]4, and [LFe(μ-O)(μ-OAc)FeL][X]2 (where L – aminopyridine ligand, X−=OTf−, SbF6−, ClO4−) are capable of efficiently conducting aerobic oxidative coupling of 2-naphthols in an asymmetric fashion, with formation of the corresponding enantiomerically enriched BINOLs (up to 56% ee) in good yields (up to 94% within 24h), using as little as 1mol% of the catalyst. The effect of ligand substitutents, solvent, counteranion, 2-naphthol structure, and oxygen pressure on the catalytic performance has been systematically examined.

Revised CHARMM force field parameters for iron-containing cofactors of photosystem II.

Photosystem II is a complex protein-cofactor machinery that splits water molecules into molecular oxygen, protons, and electrons. All-atom molecular dynamics simulations have the potential to contribute to our general understanding of how photosystem II works. To perform reliable all-atom simulations, we need accurate force field parameters for the cofactor molecules. We present here CHARMM bonded and non-bonded parameters for the iron-containing cofactors of photosystem II that include a six-coordinated heme moiety coordinated by two histidine groups, and a non-heme iron complex coordinated by bicarbonate and four histidines. The force field parameters presented here give water interaction energies and geometries in good agreement with the quantum mechanical target data. © 2017 Wiley Periodicals, Inc.

Selective C-H Bond Oxidation Catalyzed by the Fe-bTAML Complex: Mechanistic Implications.

Nonheme iron complexes bearing tetradentate N-atom-donor ligands with cis labile sites show great promise for chemoselective aliphatic C-H hydroxylation. However, several challenges still limit their widespread application. We report a mechanism-guided development of a peroxidase mimicking iron complex based on the bTAML macrocyclic ligand framework (Fe-bTAML: biuret-modified tetraamido macrocyclic ligand) as a catalyst to perform selective oxidation of unactivated 3° bonds with unprecedented regioselectivity (3°:2° of 110:1 for adamantane oxidation), high stereoretention (99%), and turnover numbers (TONs) up to 300 using mCPBA as the oxidant. Ligand decomposition pathways involving acid-induced demetalation were identified, and this led to the development of more robust and efficient Fe-bTAML complexes that catalyzed chemoselective C-H oxidation. Mechanistic studies, which include correlation of the product formed with the FeV(O) reactive intermediates generated during the reaction, indicate that the major pathway involves the cleavage of C-H bonds by FeV(O). When these oxidations were performed in the presence of air, the yield of the oxidized product doubled, but the stereoretention remained unchanged. On the basis of 18O labeling and other mechanistic studies, we propose a mechanism that involves the dual activation of mCPBA and O2 by Fe-bTAML, leading to formation of the FeV(O) intermediate. This high-valent iron oxo remains the active intermediate for most of the reaction, resulting in high regio- and stereoselectivity during product formation.

DNA Cleavage through Reductive Dioxygen Activation by Iron-Bleomycin Mimics with Carboxamido Ligation: Correlation between DNA Cleavage Efficacy and Redox Potential

DNA cleavage by a series of nonheme iron complexes supported by pentadentate carboxamido ligands, dpaqR (R = OMe, H, Cl, and NO2), was evaluated in the presence of a reducing agent under air and in the presence of hydrogen peroxide. Cleavage efficiency clearly increased as redox potential became more positive. These results provide an opportunity for the designing of Bleomycin mimics with higher activity.

Oxidation chemistry of C–H bond by mononuclear iron complexes derived from tridentate ligands containing phenolato function

A family of phenolato-based nonheme mononuclear iron(III) complexes, [FeIII(Ln)Cl2](1–4) (n=1, 2, 3, and 4) derived from tridentate ligands LnH (where L1H=2-((2-phenyl-2-(pyridine-2-yl)hydrazono)methylphenol, L2H=2-((2-phenyl-2-(pyridine-2-yl)hyrazono)nitrophenol, L3H=4-methoxy-2-((2-phenyl-2-(pyridin-2-yl)hydrazono) methyl) phenol and L4H=2,4-di-tert-butyl-6-((2-phenyl-2-(pyridin-2-yl)hydrazono)methyl)phenol and H was dissociable proton) were synthesized and characterized by different spectroscopic methods. The molecular structure of [Fe(L4)Cl2](4) was determined by X-ray crystallography. The electronic structures of complexes 2 and 4 were investigated by DFT and TD-DFT calculations. All complexes were employed as catalyst for C–H bond oxidation utilizing H2O2 as an oxidant. Effect of the substituents on the phenyl ring containing phenolato function was scrutinized for efficiency and selectivity of the oxidation process. Role of key intermediate FeIII–OOH and FeIVO was also be described.

Non-heme iron(III) complex with tridentate ligand: Synthesis, structures and catalytic oxidations of alkanes

We report synthesis and characterization of a mononuclear iron(III) complex [Fe(LH2)Cl2]+, 1 having tridentate ligand LH2 and their application in oxidation of alkanes. Complex, 1 was characterized by various analytical, spectroscopic, electrochemical, crystallographic and theoretical studies. The molecular structure determination showed the presence of distorted square pyramidal FeN3Cl2 coordination sphere. Selective oxidation of benzyl alcohol, fluorene, adamantane, 1-phenyl ethanol and n-octane in presence of catalytic amount [FeIII(LH2)Cl2]+ with H2O2 under mild conditions give products in good to excellent yields through FeIVO intermediate. Several studies were done to support the reactive intermediate. Generation of FeIVO intermediate was also supported by UV–visible titration of [FeIII(LH2)Cl2]+ and H2O2 at low temperature and their visual colour change from red (500nm, ɛ=1050M−1cm−1) to green (770nm, ɛ=153M−1cm−1).

Oxidation of alkane and alkene moieties with biologically inspired nonheme iron catalysts and hydrogen peroxide: from free radicals to stereoselective transformations.

The selective oxidation of hydrocarbons is a challenging reaction for synthetic chemists, but common in nature. Iron oxygenases activate the O-O bond of dioxygen to perform oxidation of alkane and alkenes moieties with outstanding levels of regio-, chemo- and stereoselectivity. Along a bioinspired approach, iron coordination complexes which mimic structural and reactivity aspects of the active sites of nonheme iron oxygenases have been explored as oxidation catalysts. This review describes the evolution of this research field, from the early attempts to reproduce the basic reactivity of nonheme iron oxygenases to the development of effective iron oxidation catalysts. The work covers exclusively nonheme iron complexes which rely on H2O2 or O2 as terminal oxidants. First, it delineates the key steps and the essential catalyst design principles required to activate the peroxide bond at nonheme iron centers without (or at least minimizing) the release of free-diffusing radicals. It follows with a critical description of the mechanistic pathways which govern the reaction between iron complexes and H2O2 to generate the oxidizing species. Eventually, the work presents a state-of-the-art report on the use of these catalysts in aliphatic C-H oxidation, olefin epoxidation and alkene syn-dihydroxylation, under substrate-limiting conditions. A special focus is given on the main strategies elaborated to tune catalyst activity and selectivity by modification of its structure. The work is concluded by a concise discussion on the essential progresses of these oxidation catalysts together with the challenges that remain still to be tackled.

Computational analysis of site differences in selective aliphatic C-H hydroxylation by nonheme iron-oxo complexes.

Selective C-H hydroxylation by nonheme iron complexes offers a promising method in the field of organic synthesis. Aliphatic C-H bond oxidation reactions of pivalate (R) catalyzed by [Fe(S,S-PDP)(CH3CN)2]2+ (CAT1) were examined using the density functional theory. Our calculations of the CH3CN solvent agree with the experimental findings. However, it was observed that the gas-phase results did not replicate selective C-H hydroxylation observed experimentally when CAT1 catalyzed hydrocarbon oxidations by H2O2via an HO-FeV[double bond, length as m-dash]O oxidant (CAT1a). We inferred that the difference was mainly from hydrogen bonding formation, (CAT1a) O-HO[double bond, length as m-dash]C (R), in certain gaseous H-abstraction transition states (TSH). Then, the appearance of the stronger (CAT1a) O-HN[triple bond, length as m-dash]CCH3-solvent weakened the aforementioned interaction, leading to C-H activation influenced primarily by their electronic and steric properties. Such a deduction explained the same selective C-H found in both phases of reactions with CAT1b, a cyclic ferric peracetate oxidant, by the reason of TSH without the influence of H-bonding. Another interesting finding was that the commonly recognized radical intermediate was further isomerized by a favorable electron rearrangement. Thus, the subsequent OH-rebound behavior proceeded by an electrostatic interaction. This study provides mechanistic clues for modifying regioselective C-H hydroxylation for molecule synthesis applications.

Role of electron transfer processes in the oxidation of aryl sulfides catalyzed by nonheme iron complexes

ABSTRACTThe oxidation of a series of aryl 1-methyl-1-phenylethyl sulfides with H2O2 catalyzed by the two tetradentate nonheme-iron complexes [(PDP)FeII(SbF6)2] and [(BPMCN)FeII(OTf)2] occurs by an electron transfer-oxygen transfer (ET/OT) mechanism as supported by the observation of products deriving from fragmentation of the corresponding radical cations in association with S-oxidation products (sulfoxides).

A bioinspired iron catalyst for nitrate and perchlorate reduction.

Nitrate and perchlorate have considerable use in technology, synthetic materials, and agriculture; as a result, they have become pervasive water pollutants. Industrial strategies to chemically reduce these oxyanions often require the use of harsh conditions, but microorganisms can efficiently reduce them enzymatically. We developed an iron catalyst inspired by the active sites of nitrate reductase and (per)chlorate reductase enzymes. The catalyst features a secondary coordination sphere that aids in oxyanion deoxygenation. Upon reduction of the oxyanions, an iron(III)-oxo is formed, which in the presence of protons and electrons regenerates the catalyst and releases water.

Biological inspiration for reduction

Catalysis Microorganisms have evolved sophisticated enzymatic machinery to reduce perchlorate and nitrate ions. Although the energetics of the pathways are different, the heme-containing active sites of the corresponding reductase enzymes are remarkably similar. Ford et al. constructed an inorganic catalyst to mediate these reactions based on these active sites, using a nonheme iron complex. A secondary coordination sphere near the iron center aligned the nitrate or perchlorate oxyanions and formed an iron-oxo complex. Regenerating the catalyst in the presence of protons and electrons released water—a potentially much more sustainable process than reduction strategies that require the use of harsh reagents. Science , this issue p. [741][1] [1]: /lookup/doi/10.1126/science.aah6886

Synthesis, X-ray Structures, Electronic Properties, and O2/NO Reactivities of Thiol Dioxygenase Active-Site Models.

Mononuclear non-heme iron complexes that serve as structural and functional mimics of the thiol dioxygenases (TDOs), cysteine dioxygenase (CDO) and cysteamine dioxygenase (ADO), have been prepared and characterized with crystallographic, spectroscopic, kinetic, and computational methods. The high-spin Fe(II) complexes feature the facially coordinating tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (Ph2TIP) ligand that replicates the three histidine (3His) triad of the TDO active sites. Further coordination with bidentate l-cysteine ethyl ester (CysOEt) or cysteamine (CysAm) anions yielded five-coordinate (5C) complexes that resemble the substrate-bound forms of CDO and ADO, respectively. Detailed electronic-structure descriptions of the [Fe(Ph2TIP)(LS,N)]BPh4 complexes, where LS,N = CysOEt (1) or CysAm (2), were generated through a combination of spectroscopic techniques [electronic absorption, magnetic circular dichroism (MCD)] and density functional theory (DFT). Complexes 1 and 2 decompose in the presence of O2 to yield the corresponding sulfinic acid (RSO2H) products, thereby emulating the reactivity of the TDO enzymes and related complexes. Rate constants and activation parameters for the dioxygenation reactions were measured and interpreted with the aid of DFT calculations for O2-bound intermediates. Treatment of the TDO models with nitric oxide (NO)-a well-established surrogate of O2-led to a mixture of high-spin and low-spin {FeNO}7 species at low temperature (-70 °C), as indicated by electron paramagnetic resonance (EPR) spectroscopy. At room temperature, these Fe/NO adducts convert to a common species with EPR and infrared (IR) features typical of cationic dinitrosyl iron complexes (DNICs). To complement these results, parallel spectroscopic, computational, and O2/NO reactivity studies were carried out using previously reported TDO models that feature an anionic hydrotris(3-phenyl-5-methyl-pyrazolyl)borate (Ph,MeTp-) ligand. Though the O2 reactivities of the Ph2TIP- and Ph,MeTp-based complexes are quite similar, the supporting ligand perturbs the energies of Fe 3d-based molecular orbitals and modulates Fe-S bond covalency, suggesting possible rationales for the presence of neutral 3His coordination in CDO and ADO.

Direct Selective Oxidative Functionalization of C-H Bonds with H₂O₂: Mn-Aminopyridine Complexes Challenge the Dominance of Non-Heme Fe Catalysts.

Non-heme iron(II) complexes are widespread synthetic enzyme models, capable of conducting selective C–H oxidation with H2O2 in the presence of carboxylic acid additives. In the last years, structurally similar manganese(II) complexes have been shown to catalyze C–H oxidation with similarly high selectivity, and with much higher efficiency. In this mini-review, recent catalytic and mechanistic data on the selective C–H oxygenations with H2O2 in the presence of manganese complexes are overviewed. A distinctive feature of catalyst systems of the type Mn complex/H2O2/carboxylic is the existence of two alternative reaction pathways (as found for the oxidation of cumenes), one leading to the formation of alcohol, and the other to ester. The mechanisms of formation of the alcohol and the ester are briefly discussed.

Determining the Fate of a Non-Heme Iron Oxidation Catalyst Under Illumination, Oxygen, and Acid.

We analyze the stability of the non-heme water oxidation catalyst (WOC), Fe(bpmcn)Cl2 toward oxygen and illumination under nonaqueous and acidic conditions. Fe(bpmcn)Cl2 has been previously used as a C-H activation catalyst, a homogeneous WOC, and as a cocatalyst anchored to WO3 for photoelectrochemical water oxidation. This paper reports that the ligand dissociates at pH 1 with a rate constant k = 19.8(2) × 10-3 min-1, resulting in loss of catalytic activity. The combination of UV-vis experiments, 1H NMR spectroscopy, and cyclic voltammetry confirm free bpmcn and Fe2+ present in solution under acidic conditions. Even under nonaqueous conditions, both oxygen and illumination together show slow oxidation of iron over the course of a few hours, consistent with forming an Fe3+-O2- intermediate as corroborated by resonance-enhanced Raman spectroscopy, with a rate constant of k = 3.03(8) × 10-3 min-1. This finding has implications in both the merits of non-heme iron complexes as WOCs as well as cocatalysts in photoelectrochemical schemes: the decomposition mechanisms may include both anchoring group hydrolysis and instability under illumination.

Influence of Ligand Architecture in Tuning Reaction Bifurcation Pathways for Chlorite Oxidation by Non-Heme Iron Complexes.

Reaction bifurcation processes are often encountered in the oxidation of substrates by enzymes and generally lead to a mixture of products. One particular bifurcation process that is common in biology relates to electron transfer versus oxygen atom transfer by high-valent iron(IV)-oxo complexes, which nature uses for the oxidation of metabolites and drugs. In biomimicry and bioremediation, an important reaction relates to the detoxification of ClOx- in water, which can lead to a mixture of products through bifurcated reactions. Herein we report the first three water-soluble non-heme iron(II) complexes that can generate chlorine dioxide from chlorite at ambient temperature and physiological pH. These complexes are highly active oxygenation oxidants and convert ClO2- into either ClO2 or ClO3¯ via high-valent iron(IV)-oxo intermediates. We characterize the short-lived iron(IV)-oxo species and establish rate constants for the bifurcation mechanism leading to ClO2 and ClO3- products. We show that the ligand architecture of the metal center plays a dominant role by lowering the reduction potential of the metal center. Our experiments are supported by computational modeling, and a predictive valence bond model highlights the various factors relating to the substrate and oxidant that determine the bifurcation pathway and explains the origins of the product distributions. Our combined kinetic, spectroscopic, and computational studies reveal the key components necessary for the future development of efficient chlorite oxidation catalysts.

Mimicking the Aromatic-Ring-Cleavage Activity of Gentisate-1,2-Dioxygenase by a Nonheme Iron Complex.

Gentisate-1,2-dioxygenase (GDO), a nonheme iron enzyme in the cupin superfamily, catalyzes the cleavage of the aromatic-ring of 2,5-dihydroxybenzoic acid (gentisic acid) to form maleylpyruvic acid in the microbial aerobic degradation of aromatic compounds. To develop a functional model of GDO, we have isolated a nonheme iron(II) complex, [(TpPh2 )FeII (DHN-H)] (TpPh2 =hydrotris(3,5-diphenylpyrazole-1-yl)borate, DHN-H=1,4-dihydroxy-2-naphthoate). In the reaction with O2 , the biomimetic complex oxidatively cleaves the aromatic ring of the coordinated substrate with the incorporation of both the oxygen atoms from molecular oxygen into the cleavage product. The presence of para-hydroxy group on the substrate plays a crucial role in directing the aromatic-ring cleaving reaction.

Mimicking the Aromatic‐Ring‐Cleavage Activity of Gentisate‐1,2‐Dioxygenase by a Nonheme Iron Complex

AbstractGentisate‐1,2‐dioxygenase (GDO), a nonheme iron enzyme in the cupin superfamily, catalyzes the cleavage of the aromatic‐ring of 2,5‐dihydroxybenzoic acid (gentisic acid) to form maleylpyruvic acid in the microbial aerobic degradation of aromatic compounds. To develop a functional model of GDO, we have isolated a nonheme iron(II) complex, [(TpPh2)FeII(DHN‐H)] (TpPh2=hydrotris(3,5‐diphenylpyrazole‐1‐yl)borate, DHN‐H=1,4‐dihydroxy‐2‐naphthoate). In the reaction with O2, the biomimetic complex oxidatively cleaves the aromatic ring of the coordinated substrate with the incorporation of both the oxygen atoms from molecular oxygen into the cleavage product. The presence of para‐hydroxy group on the substrate plays a crucial role in directing the aromatic‐ring cleaving reaction.

Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes: Structural, Spectroscopic, and Mechanistic Investigations.

The synthesis and reactivity of a series of mononuclear nonheme iron complexes that carry out intramolecular aromatic C-F hydroxylation reactions is reported. The key intermediate prior to C-F hydroxylation, [FeIV(O)(N4Py2Ar1)](BF4)2 (1-O, Ar1 = -2,6-difluorophenyl), was characterized by single-crystal X-ray diffraction. The crystal structure revealed a nonbonding C-H···O═Fe interaction with a CH3CN molecule. Variable-field Mössbauer spectroscopy of 1-O indicates an intermediate-spin (S = 1) ground state. The Mössbauer parameters for 1-O include an unusually small quadrupole splitting for a triplet FeIV(O) and are reproduced well by density functional theory calculations. With the aim of investigating the initial step for C-F hydroxylation, two new ligands were synthesized, N4Py2Ar2 (L2, Ar2 = -2,6-difluoro-4-methoxyphenyl) and N4Py2Ar3 (L3, Ar3 = -2,6-difluoro-3-methoxyphenyl), with -OMe substituents in the meta or ortho/para positions with respect to the C-F bonds. FeII complexes [Fe(N4Py2Ar2)(CH3CN)](ClO4)2 (2) and [Fe(N4Py2Ar3)(CH3CN)](ClO4)2 (3) reacted with isopropyl 2-iodoxybenzoate to give the C-F hydroxylated FeIII-OAr products. The FeIV(O) intermediates 2-O and 3-O were trapped at low temperature and characterized. Complex 2-O displayed a C-F hydroxylation rate similar to that of 1-O. In contrast, the kinetics (via stopped-flow UV-vis) for complex 3-O displayed a significant rate enhancement for C-F hydroxylation. Eyring analysis revealed the activation barriers for the C-F hydroxylation reaction for the three complexes, consistent with the observed difference in reactivity. A terminal FeII(OH) complex (4) was prepared independently to investigate the possibility of a nucleophilic aromatic substitution pathway, but the stability of 4 rules out this mechanism. Taken together the data fully support an electrophilic C-F hydroxylation mechanism.

A mononuclear non-heme-iron dioxygen-carrying protein?

The ability of mononuclear non-heme iron complexes to function as molecular oxygen transporters is investigated by density functional theory. The factors governing the efficiency of the reversible binding of dioxygen at the active site of the dinuclear non-heme iron enzyme hemerythrin, including antiferromagnetic coupling and the conversion of dioxygen to hydroperoxo by a proton coupled 2-electron transfer mechanism, are revisited and considered as possible tools in mononuclear non-heme complexes. Several mononuclear non-heme model complexes, including active sites of enzymes already known to interact with dioxgenic ligands, are constructed and the molecular oxygen transportation capabilities of these complexes are examined computationally. The high-spin nature of the ground state of these complexes implies an intrinsic kinetic lability of the oxy structures, as also evident from potential energy surface calculations towards iron-dioxygen cleavage. Proton affinities as calibrated with reference compounds showed that these complexes are highly unlikely to undergo protonation to form hydroperoxo-like adducts. Mixed superoxo descriptions of the dissociated dioxygenic ligands in all complexes add to the overall conclusion that these model structures are significantly disadvantaged in any attempt to be employed for molecular oxygen transportation.

Nonheme iron complex-catalyzed efficient alcohol oxidation by t-BuOOH with N-hydroxyphthalimide (NHPI) as co-catalyst: Implication of high valent iron-oxo species

Two iron catalysts ([Fe(bpc)Cl2][Et4N] (1a) and [Fe(Me2bpb)Cl2][Et3NH] (1b)) displayed efficient catalysis in oxidation of various alcohols to the corresponding carbonyl products using t-BuOOH as an oxidant in the presence of N-hydroxyphthalimide (NHPI) under mild conditions. 1a having an electron-withdrawing group showed a little better catalytic activity than that of 1b with an electron-donating group. The mechanistic studies through Hammett plot, deuterium isotope effect, and the use of 2-methyl-1-phenylprop-2-yl hydroperoxide (MPPH) as a mechanistic probe suggested that the reactive oxidants responsible for the alcohol oxidation possibly involved FeIVO species, alkoxy radical (RO), and phthalimide N-oxyl radical (PINO). On the other hand, the presence of imidazole increased the heterolytic cleavage of Fe-OOR intermediate to form FeVO species and accelerated its OO bond cleavage rate. In particular, the formation of FeVO intermediate via the heterolytic cleavage of Fe-OOR species in the presence of imidazole in the catalytic oxidation systems of nonheme iron complexes with t-BuOOH was substantialized, for the first time, to the best of our knowledge.