Porphyrin Cation Radical Complex Research Articles

Substitution effects on olefin epoxidation catalyzed by Oxoiron(IV) porphyrin π-cation radical complexes: A dft study.

The effects of peripheral fluorine atoms on epoxidation reactions of ethylene by oxoiron(IV) porphyrin cation radical complex in the quartet and sextet spin multiplicities are systematically investigated using the DFT method. The overall reaction routes are determined using a model system of ethylene and Fe(IV)OCl-porphyrin with substituted fluorine atoms. By obtaining the energy diagrams and electron- and spin-density difference contour maps of the transition states and intermediate compounds, we confirm that the electron-withdrawing by peripheral fluorine atoms enhances the reactivity as the number of fluorine atoms increases, as is observed experimentally. The intersystem crossing between the quartet and sextet spin multiplicities is discussed by means of the intrinsic reaction coordinate method. We conclude that the rate-determining step is located at the first transition state (TS1) for the activation of CC and FeO bonds, and the ground electronic state changes from quartet to sextet around the TS1. © 2019 Wiley Periodicals, Inc.

Hydrogen Atom vs. Hydride Transfer in Cytochrome P450 Oxidations: A Combined Mass Spectrometry and Computational Study

Biomimetic models of short‐lived enzymatic reaction intermediates can give useful insight into the properties and coordination chemistry of transition metal complexes. In this work, we investigate a high‐valent iron(IV)‐oxo porphyrin cation radical complex, namely [FeIV(O)(TPFPP+·)]+, for which TPFPP is the dianion of 5,10,15,20‐tetrakis(pentafluorophenyl) porphyrin. The [FeIV(O)(TPFPP+·)]+ ion was studied by ion‐molecule reactions in a Fourier transform ion cyclotron resonance mass spectrometer through reactivities with 1,3,5‐cycloheptatriene, 1,3‐cyclohexadiene and toluene. The different substrates give dramatic changes in reaction mechanism and efficiencies, whereby cycloheptatriene leads to hydride transfer, whereas cyclohexadiene and toluene react through hydrogen atom abstraction. Detailed computational studies point to major differences in ionization energy, as well as C–H bond energies of the substrates that influence the hydrogen atom abstraction vs. electron transfer pathways. The various variables that determine the pathways for hydride transfer vs. hydrogen atom transfer are elucidated and discussed.

A comprehensive test set of epoxidation rate constants for iron(iv)-oxo porphyrin cation radical complexes.

Cytochrome P450 enzymes are heme based monoxygenases that catalyse a range of oxygen atom transfer reactions with various substrates, including aliphatic and aromatic hydroxylation as well as epoxidation reactions. The active species is short-lived and difficult to trap and characterize experimentally, moreover, it reacts in a regioselective manner with substrates leading to aliphatic hydroxylation and epoxidation products, but the origin of this regioselectivity is poorly understood. We have synthesized a model complex and studied it with low-pressure Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometry (MS). A novel approach was devised using the reaction of [FeIII(TPFPP)]+ (TPFPP = meso-tetrakis(pentafluorophenyl)porphinato dianion) with iodosylbenzene as a terminal oxidant which leads to the production of ions corresponding to [FeIV(O)(TPFPP+˙)]+. This species was isolated in the gas-phase and studied in its reactivity with a variety of olefins. Product patterns and rate constants under Ideal Gas conditions were determined by FT-ICR MS. All substrates react with [FeIV(O)(TPFPP+˙)]+ by a more or less efficient oxygen atom transfer process. In addition, substrates with low ionization energies react by a charge-transfer channel, which enabled us to determine the electron affinity of [FeIV(O)(TPFPP+˙)]+ for the first time. Interestingly, no hydrogen atom abstraction pathways are observed for the reaction of [FeIV(O)(TPFPP+˙)]+ with prototypical olefins such as propene, cyclohexene and cyclohexadiene and also no kinetic isotope effect in the reaction rate is found, which suggests that the competition between epoxidation and hydroxylation - in the gas-phase - is in favour of substrate epoxidation. This notion further implies that P450 enzymes will need to adapt their substrate binding pocket, in order to enable favourable aliphatic hydroxylation over double bond epoxidation pathways. The MS studies yield a large test-set of experimental reaction rates of iron(iv)-oxo porphyrin cation radical complexes, so far unprecedented in the gas-phase, providing a benchmark for calibration studies using computational techniques. Preliminary computational results presented here confirm the observed trends excellently and rationalize the reactivities within the framework of thermochemical considerations and valence bond schemes.

Spectroscopic and Mechanistic Studies on Oxidation Reactions Catalyzed by the Functional Model SR Complex for Cytochrome P450: Influence of Oxidant, Substrate, and Solvent

Kinetic and mechanistic studies on the formation of an oxoiron(IV) porphyrin cation radical bearing a thiolate group as proximal ligand are reported. The SR complex, a functional enzyme mimic of P450, was oxidized in peroxo-shunt reactions under different experimental conditions with variation of solvent, temperature, and identity and excess of oxidant in the presence of different organic substrates. Through the application of a low-temperature rapid-scan stopped-flow technique, the reactive intermediates in the SR catalytic cycle, such as the initially formed SR acylperoxoiron(III) complex and the SR high-valent iron(IV) porphyrin cation radical complex [(SR(*+))Fe(IV)=O], were successfully identified and kinetically characterized. The oxidation of the SR complex under catalytic conditions provided direct spectroscopic information on the reactivity of [(SR(.+))Fe(IV)=O] towards the oxidation of selected organic substrates. Because the catalytically active species is a synthetic oxoiron(IV) porphyrin cation radical bearing a thiolate proximal group, the effect of the strong electron donor ligand on the formation and reactivity/stability of the SR high-valent iron species is addressed and discussed in the light of the reactivity pattern observed in substrate oxygenation reactions catalyzed by native P450 enzyme systems.

Probing the Cytochrome P450-like Reactivity of High-Valent Oxo Iron Intermediates in the Gas Phase

Electrospray ionization in combination with Fourier transform ion cyclotron resonance spectrometry is used to prepare and characterize at a molecular level high-valent oxoiron intermediates formed in the reaction of [(TPFPP)Fe(III)]Cl (TPFPP= meso-tetrakis(pentafluorophenyl)porphinato dianion) (1-Cl) with H(2)O(2) in methanol. The intrinsic reactivity in the gas phase of the iron(IV) oxo porphyrin cation radical complex, [(TPFPP)(.+)Fe(IV)=O](+), has been probed toward selected substrates (S), chosen among naturally occurring and model compounds. Whereas CO and cyclohexane proved to be unreactive, olefins, sulfides, amines, and phosphites all undergo oxygen atom transfer in the gas phase yielding the reduction product 1 and/or an adduct ion ([1-S](+)). The reaction efficiencies show a qualitative correlation with the oxophilic character of the active site of S. A notable exception is nitric oxide, which displays a remarkably high reactivity, in line with the important role of NO reactions with iron porphyrin complexes. Furthermore, subsidiary information on the neat association reaction of 1 with selected ligands (L) has been obtained by a kinetic study showing that both the efficiency and the extent of ligation toward the naked ion 1 depend on the electron-donating ability of L.

Multi-state epoxidation of ethene by cytochrome P450: a quantum chemical study.

The epoxidation of ethene by a model for Compound I of cytochrome P450, studied by the use of density functional B3LYP calculations, involves two-state reactivity (TSR) with multiple electromer species, hence "multi-state epoxidation". The reaction is found to proceed in stepwise and effectively concerted manners. Several reactive states are involved; the reactant is an (oxo)iron(IV) porphyrin cation radical complex with two closely lying spin states (quartet and doublet), both of which react with ethene to form intermediate complexes with a covalent C-O bond and a carbon-centered radical (radical intermediates). The radical intermediates exist in two electromers that differ in the oxidation state of iron; Por(+)(*)Fe(III)OCH(2)CH(2)(*) and PorFe(IV)OCH(2)CH(2)(*) (Por = porphyrin). These radical intermediates exist in both the doublet- and quartet spin states. The quartet spin intermediates have substantial barriers for transformation to the quartet spin PorFe(III)-epoxide complex (2.3 kcal mol(-)(1) for PorFe(IV)OCH(2)CH(2)(*) and 7.2 kcal mol(-)(1) for Por(+)(*)Fe(III)OCH(2)CH(2)(*)). In contrast, the doublet spin radicals collapse to the corresponding PorFe(III)-epoxide complex with virtually no barriers. Consequently, the lifetimes of the radical intermediates are much longer on the quartet- than on the doublet spin surface. The loss of isomeric identity in the epoxide and rearrangements to other products arise therefore mostly, if not only, from the quartet process, while the doublet state epoxidation is effectively concerted (Scheme 7). Experimental trends are discussed in the light of the computed mechanistic scheme, and a comparison is made with closely related mechanistic schemes deduced from experiment.

Participation of Two Distinct Hydroxylating Intermediates in Iron(III) Porphyrin Complex-Catalyzed Hydroxylation of Alkanes

We have obtained evidence that acylperoxo-iron(III) porphyrin complexes 1a are involved as reactive hydroxylating intermediates in the hydroxylation of alkanes by m-chloroperoxybenzoic acid (m-CPBA) catalyzed by electron-deficient iron(III) porphyrin complexes containing chloride as an anionic axial ligand in a solvent mixture of CH2Cl2 and CH3CN at −40 °C. In addition to the intermediacy of 1a, oxoiron(IV) porphyrin cation radical complexes 2 are formed as the reactive hydroxylating intermediates in the alkane hydroxylations by m-CPBA catalyzed by the iron(III) porphyrin complexes containing triflate (CF3SO3-) as an anionic axial ligand under the same reaction conditions. In line with the recent proposal by Newcomb, Coon, Vaz, and co-workers for cytochrome P-450 reactions, these results suggest that two distinct electrophilic oxidants such as 1a and 2 effect the alkane hydroxylations in iron porphyrin models, depending on the reaction conditions such as the nature of the anionic axial ligands of iron(III...

Evidence for the Participation of Two Distinct Reactive Intermediates in Iron(III) Porphyrin Complex-Catalyzed Epoxidation Reactions

We have studied the competitive epoxidations of olefins with cis- and trans-stilbenes and with cyclooctene and trans-stilbene in iron porphyrin complex-catalyzed epoxidation reactions by H2O2, tert-butyl hydroperoxide (t-BuOOH), and m-chloroperoxybenzoic acid (m-CPBA) in protic solvent (i.e., a solvent mixture of CH3OH and CH2Cl2) and aprotic solvent (i.e., a solvent mixture of CH3CN and CH2Cl2) at room temperature under catalytic reaction conditions. The competitive epoxidations were also carried out with in situ generated high-valent iron(IV) oxo porphyrin cation radical complexes in aprotic solvent under stoichiometric reaction conditions. By determining the ratios of epoxide products formed in the competitive epoxidations, we were able to conclude unambiguously that the reactive species generated in protic solvent are high-valent iron(IV) oxo porphyrin cation radical complexes 3 and the intermediates formed in aprotic solvent are oxidant−iron porphyrin intermediates 2. A protic solvent such as methano...

Biomimetic Alkane Hydroxylations by an Iron(III) Porphyrin Complex with H2O2 and by a High-Valent Iron(IV) Oxo Porphyrin Cation Radical Complex

An iron(III) porphyrin complex with highly electron-withdrawing substituents on the porphyrin ligand efficiently catalyzes the hydroxylation of alkanes by H2O2 via enzyme mimetic oxidation reactions in aprotic solvent. An “isolated” high-valent iron(IV) oxo porphyrin cation radical intermediate, prepared in situ by reaction of the iron porphyrin complex with m-CPBA at −40 °C, is capable of activating C−H bonds of alkanes to give oxygenated products efficiently. The hydroxylating intermediate generated in the catalytic H2O2 reaction is evidenced to be the high-valent iron(IV) oxo porphyrin cation radical species.

Significant Electronic Effect of Porphyrin Ligand on the Reactivities of High-Valent Iron(IV) Oxo Porphyrin Cation Radical Complexes.

High-valent iron(IV) oxo porphyrin cation radical complexes containing a series of substituents at the meso position of the porphyrin ring (i.e., electron-donating and -withdrawing substituents on phenyl groups) were prepared and used in oxygen atom transfer reactions to elucidate the electronic effect of porphyrin ligands on the reactivities of iron porphyrin complexes. The reactions that we studied with the in situ generated high-valent iron oxo porphyrins were (1) the relative reactivities of the intermediates toward oxygen atom transfer and ROOH disproportionation (ROOH = hydrogen peroxide and tert-butyl hydroperoxide), (2) the mechanism of heterolytic versus homolytic O-O bond cleavage of hydroperoxides, (3) the dependence of oxidizing power of the intermediates on the electronic nature of porphyrin ligands, and (4) the relative rates between oxygen atom transfer and oxygen exchange with labeled H(2)(18)O. We found from these reactivity studies that (1) a high-valent iron oxo porphyrin complex containing electron-donating substituents reacts fast with ROOH in a competitive reaction performed with a mixture of olefin and ROOH, whereas a high-valent iron oxo porphyrin containing electron-withdrawing substituents transfers its oxygen atom to olefin to give an epoxide product at a fast rate, (2) the O-O bond of hydroperoxides is homolytically cleaved by iron porphyrin complexes in aprotic solvent, (3) a high-valent iron oxo complex of electron-deficient porphyrin ligand is a more powerful oxidizing species than that of electron-rich porphyrin ligand in alkane hydroxylation reactions, and (4) the presence of electron-donating substituents on a porphyrin ligand gives a relatively high (18)O incorporation from labeled H(2)(18)O into an oxygenated product when a mixture of olefin and H(2)(18)O is added to a reaction solution containing a high-valent iron oxo intermediate, whereas only a small amount of (18)O incorporation is observed with iron porphyrin complexes containing electron-withdrawing substituents. These results clearly demonstrate that the electronic nature of iron porphyrin complexes is an important factor in determining the reactivities of iron porphyrin complexes in oxygen atom transfer reactions.

Water-Soluble Iron Porphyrin Complex-Catalyzed Epoxidation of Olefins with Hydrogen Peroxide and tert-Butyl Hydroperoxide in Aqueous Solution

Catalytic epoxidation of olefins with H2O2 and t-BuOOH has been studied in the presence of a water-soluble iron(III) porphyrin complex, (5,10,15,20-tetrakis(2,6-dichloro-3-sulfonatophenyl)porphinato)iron(III) [Fe(TDCPPS)], in buffered aqueous solutions. Epoxides are the predominant products at low pH values, and the formation of the oxide products is found to depend on the pH of the reaction solutions. A high-valent iron(IV) oxo porphyrin cation radical complex is proposed as a reactive intermediate responsible for the olefin epoxidation.

Reaction profile of the last step in cytochrome P-450 catalysis revealed by studies of model complexes

A series of oxoiron(IV) porphyrin cation radical complexes was investigated as compound I analogs of cytochrome P-450. Both the spectroscopic features and the reactivities of the complexes in oxygen atom transfer to olefins were examined as a function of only one variable, the axial ligand trans to the oxoiron(IV) bond. The results disclosed two important kinetic steps – electron transfer from olefin to oxoiron(IV) and intramolecular electron transfer from metal to porphyrin radical – which are affected differently by the axial ligands. The large kinetic barrier of the latter step in the reaction of olefins with the perchlorato-bound oxoiron(IV) porphyrin cation radical complex enabled the trapping of a reaction intermediate in which the metal, but not the porphyrin radical, is reduced. The first electron transfer step is probably followed by σ-bond formation, which readily accounts for formation of isomerized organic products at low temperatures. It is finally postulated that part of the enhanced oxygenation activities of cytochrome P-450 monooxygenases and chloroperoxidases is due to a lowering of the energy barrier for the second electron transfer step via participation of their redox-active cysteinate ligand.

Molecular orbital study of the hydroxylation of benzene and monofluorobenzene catalysed by iron-oxo porphyrin π cation radical complexes

The reaction mechanism for the hydroxylation of benzene and monofluorobenzene, catalysed by a ferryl-oxo porphyrin cation radical complex (compound) is described by electronic structure calculations in local spin density approximation. The active site of the enzyme is modelled as a six-coordinated (Por+)Fe(IV)O a2u complex with imidazole or H3CS– as the axial ligand. The substrates under study are benzene and fluorobenzene, with the site of attack in para, meta and ortho position with respect to F. Two reaction pathways are investigated, with direct oxygen attack leading to a tetrahedral intermediate and arene oxide formation as a primary reaction step. The calculations show that the arene oxide pathway is distinctly less probable, that hydroxylation by an H3CS––coordinated complex is energetically favoured compared with imidazole, and that the para position with respect to F is the preferred site for hydroxylation. A partial electron transfer from the substrate to the porphyrin during the reaction is obtained in all cases. The resulting charge distribution and spin density of the substrates reveal the transition state as a combination of a cation and a radical σ-adduct intermediate with slightly more radical character in the case of H3CS– as axial ligand. A detailed analysis of the orbital interactions along the reaction pathway yields basically different mechanisms for the modes of substrate–porphyrin electron transfer and rupture of the Fe–O bond. In the imidazole-coordinated complex an antibonding π*(Fe–O) orbital is populated, whereas in the H3CS––coordinated system a shift of electron density occurs from the Fe–O bond region into the Fe–S bond.

Preparation, characterization, and reaction of novel dioxoruthenium(VI) porphyrin cation radical complexes

Novel dioxoruthenium(VI) porphyrin cation radicals were prepared in the stoichiometric oxidation of Ru[sup VI]TMP(O)[sub 2] (1) and Ru[sup VI]OEP(O)[sub 2] (2) with phenoxathiin hexachloroantimonate. [sup 2]H-NMR, UV-vis, and ESR were measured to determine the electronic structure of the oxidation products. The oxidation product (3) of 1 shows a broad Q band and a less intense and blue-shifted Soret band, suggestive of the porphyrin cation radical formation. Further, the single ESR signal for 3 at g = 2.002 at 77 K is a clear demonstration of one-electron oxidation of the porphyrin ring to form a free radical complex. The presence of two oxo ligands in 3 was confirmed in the reaction of 3 with Ph[sub 3]P under argon to give 2 mol equiv of Ph[sub 3]P[double bond]O. Very similar results were also obtained when 2 was oxidized under the same condition, and the oxidation product (4) was also assigned to be a dioxoruthenium(VI) prophyrin cation radical. The chemical shifts of 3 and 4 were determined by deuterium NMR using partially deuterated 3 and 4. On the basis of paramagnetic shifts, the radical orbitals of 3 and 4 were determined to be A[sub 1u]. Further, oxidation reactions of diphenyl sulfide and somemore » olefins were carried out with high valent ruthenium complexes (1-4), and the results show that 3 and 4 exhibit greater reactivity than 1 and 2; however, the enhancement of the reactivities are less than those expected for the complexes bearing A[sub 2u] radical orbitals. 27 refs., 5 figs., 2 tabs.« less

Dual electron-transfer reactivity of a high-spin iron(III) porphyrin cation radical complex

Easily oxidised nucleophiles, such as iodide, bromide, and 1,8-bis(dimethylamino)naphthalene, react with the diaquotetraphenylporphyrinatoiron(III) cation radical complex, [Fe(H2O)2(tpp˙)]2+, to give the corresponding tetraphenylporphyrin complex, [Fe(H2O)2(tpp)]+, while pyridine gives an entirely different product, [(tpp)FeOFe(tpp˙)]+; e.s.r. spectra and potentiometric evidence suggest that a base-dependent internal electronic isomerisation, leading to tetraphenylporphyrinato-oxoiron(IV), takes place in the latter reaction.

Synthetic models of metalloenzymes

Metal ions play an important role in the enzymic catalysis of many metalloproteins. The molecular details of the catalytic cycle are often obscured by the complexity of the biological system. It has been the goal of our research for the past few years to elucidate the mechanisms of metalloenzymes through the synthesis of simple metal complexes that mimic the structure of the active sites. The reactivity of such metal complexes have provided insights into the enzyme mechanism. Further, successful enzyme models have provided a rational basis for the construction of synthetic, biomimetic catalysts. In this lecture, recent advances in the study of active site models of carboxypeptidase A, CPA, a zinc-containing protease, and cytochrome P-450, a heme-containing monooxygenase will be described. The role of zinc in the peptidase activity of CPA has been ascribed to coordination of the substrate amide carbonyl, coordination of a nucleophilic hydroxide or even to a less specific structural role. To choose among these possibilities we have synthesized a family of metal-complexing amides which does not allow a metal-carbonyl interaction. Large zinc- and copper-mediated rate enhancements (10 410 7) for amide hydrolysis are observed with these compounds. Kinetic and titrimetric measurements indicate that the deprotonation of a metal-bound water is a component of this catalysis. A mechanism for amide hydrolysis involving nucleophilic attack of a metal hydroxide is consistent with the observed results. The catalytic cycle of cytochrome P-450 has been suggested to involve a reactive oxo-iron intermediate which is responsible for oxygen transfer to the substrate. We have prepared the first synthetic example of an iron(IV)-porphyrin cation radical complex ( 1). This species has been shown to be extraordinarily reactive toward hydrocarbons. The physico-chemical characterization of 1 and the elucidation of the mechanism of olefin epoxidation and alkane hydroxylation will be described.