Oxo Porphyrin Research Articles

"True" iron(V) and iron(VI) porphyrins: a first theoretical exploration.

We present here a first theoretical characterization of iron(V) (S = (3)/(2)) and iron(VI) (S = 0) porphyrin intermediates. The Fe(V) calculations exhibit exceptionally narrow convergence radii and we believe that for this reason they have long eluded researchers working on high-valent iron intermediates. The Fe(V)-N(nitrido) bond distance in the DFT(PW91/TZP) optimized geometry of Fe(V)(P)(N) is 1.722 A, comparable to and slightly longer than the Fe(IV)-O bond distance of 1.684 A in Fe(IV)(P)(O) and the Fe(IV)-N(imido) bond distance of 1.698 A in Fe(IV)(P)(NH). In contrast, the Fe(VI)-N(nitrido) bond distances in [Fe(VI)(P)(N)](+) (S = 0) and Fe(VI)(P)(N)(F) (S = 0) are dramatically shorter, 1.508 and 1.533 A, respectively, consistent with the formal triple bond character of the Fe(VI)-N(nitrido) bond. The nitrido ligand appears to be uniquely capable of stabilizing a "true" Fe(V) center, in the sense defined in the paper. All three unpaired electrons in Fe(V)(P)(N) are completely localized on the Fe(V)-N(nitrido) axis, with the Fe and N gross atomic spin populations being 1.579 and 1.550, respectively. In contrast, an axial ligand set consisting of an oxide and a fluoride do not stabilize an Fe(V) ground state but favor an electronic structure best described as an Fe(IV)-oxo porphyrin pi-cation radical.

The structure and spin coupling of catalase compound I: a study of noncovalent effects.

Catalase compound I contains an iron(lV)-oxo porphyrin- radical; in this species, an S = l iron-oxo unit and an S = 1/2 radical, located on the porphyrin ring, couple to give doublet and quartet states that are mixed by the zero-field splitting of the ferryl moiety. The result is a Kramer's doublet ground state with a distinctive EPR signature.

Molecular structures and electron distributions of higher-valent iron and manganese porphyrins: Density functional theory calculations and some preliminary open-shell coupled-cluster results

Density functional theory (DFT) calculations have been carried out for a variety of iron and manganese porphyrin complexes with metal oxidation states of +3 and above. In general, DFT gives very good descriptions of molecular structure and electron distributions, but appears less reliable in predictions of the relative energetics of different spin states of transition metal compounds. For instance, the fact that our calculations favor a quartet state for the five-coordinate complex, ( P ) FeCl , over a sextet state may be regarded as a shortcoming of currently available exchange-correlation functionals. This problem is corrected at the considerably more demanding spin-restricted open-shell coupled-cluster level of theory. For both +3 and +4 metal oxidation states, the manganese 3d subshells appear to be significantly more spatially contracted than the 3d subshells of analogous iron compounds. This appears to be a key factor underlying the anomalously low MnO stretching frequencies of Mn(IV) -oxo porphyrins, compared to the FeO stretching frequencies of Fe(IV) -oxo porphryins. Similarly, a dramatic ruffling-induced redistribution of unpaired spin density in the case of an A2 u-type iron(IV)-oxo porphyrin cation radical, recently reported by Deeth, has been ascribed to a metal( dxy)–porphyrin( a2 u) orbital interaction that becomes symmetry-allowed on ruffling of the porphyrin ring. If the axial ligand in a compound I species is strongly basic such as imidazolate (e.g. horseradish peroxidase) or mercaptide (chloroperoxidase and cytochrome P450), it too can be strongly noninnocent and carry a significant unpaired electron spin population. Similarly, theoretical modeling of a synthetic 'perferryl' complex, reported by Morishima and co-workers, has revealed a noninnocent axial methoxide ligand.

Biomimetic alkane hydroxylation by cobalt(iii) porphyrin complex and m-chloroperbenzoic acid

The catalytic hydroxylation of alkanes by an electron-deficient cobalt(III) porphyrin complex and m-chloroperbenzoic acid yielded alcohols as major products with a high kH/kD value, >99% retention of stereochemistry, and a high regioselectivity; a high-valent cobalt–oxo porphyrin complex was suggested as a reactive hydroxylating intermediate.

The electronic and vibrational structures of iron–oxo porphyrin with a methoxide or cysteinate axial ligand

Hybrid density functional theory (DFT) calculations for the electronic and vibrational structures of compound I species with a methoxide (MeO −) ( 1) or cysteinate (CysS −) ( 2) axial ligand are carried out in order to elucidate the natures of a methoxide-coordinating new type of compound I species (Bull. Chem. Soc. Jpn. 71 (1998) 1343) and cysteinate-coordinating compound I species of chloroperoxidase (CPO-I) and cytochrome P450s (P450-I). DFT computations of 1 and 2 demonstrate that these “anionic” ligands are a spin carrier; 70% (80%) of a spin density resides on the O (S) atom of the axial ligand and 30% (20%) is distributed on the porphyrin ring. These results suggest that for the generation of the compound I species, one electron is removed from the iron centers and the rest of the one electron is supplied from the oxidizable axial ligands instead of the iron centers or the porphyrin ring. Vibrational analyses demonstrate that the FeO bond is more strongly activated in 1 compared with 2 with the stretching mode at 849 cm −1 (878 cm −1) for the doublet state 1a ( 2a) and at 814 cm −1 (875 cm −1) in the quartet state 1b ( 2b). This reverse order of the FeO bond strength with respect to the axial donor strength should have relevance to the significantly oxidized character of the CysS − axial ligand. In conjunction with the recent results of the extensive resonance Raman (RR) studies, some interpretations of unsettled RR results for compound I of chloroperoxidase (CPO-I) and a synthetic compound I species [OFe IV(TMP ⋅+)(alcohol)] (J. Am. Chem. Soc. 113 (1991) 6542) concerning the OFe stretching frequencies are discussed.

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...

Theoretical studies on high‐valent manganese porphyrins: Toward a deeper understanding of the energetics, electron distributions, and structural features of the reactive intermediates of enzymatic and synthetic manganese‐catalyzed oxidative processes

AbstractWe present here a relatively comprehensive theoretical study, based on nonlocal density functional theory calculations, of the energetics, electron distributions, and structural features of the low‐lying electronic states of various high‐valent intermediates of manganese porphyrins. Two classes of molecules have been examined: (a) compounds with the general formula [(P)MnX2]0 (P = porphyrin; X = F, Cl, PF6) and (b) high‐valent manganese‐oxo species. For [(P)Mn(PF6)2]0, the calculations reveal a number of nearly equienergetic quartet and sextet states as the lowest states, consistent with experimental results on a comparable species, [(TMP)Mn(ClO4)2]0 (TMP = tetramesitylporphyrin). In contrast, [(P)MnCl2]0 and [(P)MnF2]0 have a single well‐defined S = 3/2 Mn(IV) ground state, again in agreement with experiment, with the three unpaired spins largely concentrated (>90%) on the manganese atom. Manganese(IV)‐oxo porphyrins have an S = 3/2 ground state, with the three unpaired spins distributed approximately 2.3:0.7 between the manganese and oxygen atoms. The metal‐to‐oxygen spin delocalization, as measured by the oxygen spin population, for MnIV = O porphyrins is less than, but still qualitatively similar to, that in analogous iron(IV)‐oxo intermediates, indicating that the MnIV = O bond is significantly weaker than the FeIV = O bond in an analogous molecule. Thus, the optimized metal—oxygen bond distances are 1.654 and 1.674 Å for (P)FeIV(O)(Py) and (P)MnIV(O)(Py), respectively (Py = pyridine). This is consistent with the experimental observation that MnIV = O stretching frequencies are over 10% lower than FeIV = O stretching frequencies for analogous compounds. For [(P)Mn(O)(PF6)]0, [(P)Mn(O)(Py)]+, and [(P)Mn(O)(F)]0, the ground states clearly correspond to a (dxy)2 Mn(V) configuration and the short Mn–O distances of 1.541, 1.546, and 1.561 Å for the three compounds, respectively, reflect the formal triple bond character of the Mn–O interaction. Interestingly, the corresponding Mn(IV)‐oxo porphyrin cation radical states are calculated to be a few tenths of an electrovolt higher than the Mn(V) ground states, suggesting that the Mn(IV)‐oxo porphyrin cation radicals are not likely to exist as ground‐state species.

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.

High-valent iron oxo porphyrin complex in the epoxidation of olefins by an iron(III) porphyrin and hydrogen peroxide in aprotic solvent

High-valent iron oxo porphyrin complex in the epoxidation of olefins by an iron(III) porphyrin and hydrogen peroxide in aprotic solvent

Influence of Substituents in Fluorobenzene Derivatives on the Cytochrome P450-Catalyzed Hydroxylation at the Adjacent Ortho Aromatic Carbon Center

In a previous study, the in vivo cytochrome P450-catalyzed regioselectivity of aromatic ring hydroxylation for a series of (poly)fluorobenzenes could be quantitatively predicted by the calculated frontier orbital density distribution in the aromatic ring [Rietjens et al. (1993) Biochemistry 32, 4801-4812]. However, the relative small fluorine, its size almost comparable to a hydrogen, is not expected to influence the regioselectivity of aromatic hydroxylation due to steric hindrance. The aim of the present study was to investigate the influence of substituents larger than a hydrogen or fluorine on the possibilities for hydroxylation at the adjacent carbon center. First, the in vivo regioselectivity of aromatic ring hydroxylation of a series of C4-substituted fluorobenzenes was investigated. The results obtained demonstrate that a chlorine and cyano C4 substituent do not hamper hydroxylation at the positions ortho to the C4 carbon atom. For 4-chloro- and 4-cyanofluorobenzene, the observed regioselectivity of aromatic hydroxylation correlated with the regioselectivity predicted on the basis of the frontier orbital density distribution. In contrast, a bromine and iodine substituent affected the hydroxylation at the adjacent ortho carbon centers, reducing it to respectively 40 and 6% of the calculated intrinsic reactivity of the carbon centers. Additional experiments were performed to investigate whether the regioselectivity of the aromatic hydroxylation of the C4-substituted fluorobenzene model compounds was influenced by changes in the cytochrome P450 enzyme pattern. Results obtained demonstrate that for these relatively small substrates the regioselectivity of their hydroxylation was not significantly influenced by several cytochrome P450 inducers. This suggests that the active sites of the cytochromes P450 catalyzing the aromatic hydroxylation do not impose a stereoselective orientation of the aromatic rings with respect to the iron-oxo porphyrin reaction center. Thus, the working hypothesis for additional experiments was that the deviations for the regioselectivity of aromatic hydroxylation observed for 4-bromo- and 4-iodofluorobenzene may be ascribed to steric hindrance by the bromine and iodine substituents hampering the attack of the cytochrome P450 iron-oxo species on the adjacent carbon centers in the benzene derivative. This working hypothesis was further tested by investigating whether useful steric correction factors could be derived from the results obtained with the series C4-substituted fluorobenzenes. These correction factors should make it possible to correct calculated relative reactivities of carbon sites for steric hindrance by substituents positioned ortho with respect to the carbon to be hydroxylated. This will make it possible to better explain and predict the regioselectivities for other chlorine-, bromine-, iodine-, and cyano-containing fluorobenzenes. The in vivo regioselectivity of aromatic ring hydroxylation of a series of five chlorine-, bromine-, iodine-, or cyano-containing fluorobenzenes did not correlate with the noncorrected calculated reactivities (r = 0.49). However, upon correction of the calculated reactivity values by using the steric correction factors, a correlation between the observed and calculated regioselectivity for the substrates of the present study was obtained (r = 0.91). Together these results strongly indicate that for the fluorobenzenes studied the main factors directing the regioselectivity of their aromatic hydroxylation are (i) the nucleophilic chemical reactivity of the site to be hydroxylated and (ii) the steric influence of the substituent ortho with respect to the site of hydroxylation. This latter effect appears to be negligible for a fluorine, chlorine, and cyano substituent but significant for a bromine and iodine substituent.

Delocalization over the heme and the axial ligands of one of the two oxidizing equivalents stored above the ferric state in the peroxidase and catalase Compound-I intermediates: indirect participation of the proximal axial ligand of iron in the oxidation reactions catalyzed by heme-based peroxidases and catalases?

A comparison of the exchange interactions arising in the peroxidase and catalase Compound I intermediates and their iron(IV)-oxo porphyrin π-cation radical models, both of which are two oxidizing equivalents above the ferric state, suggests that in the models the oxidizing equivalent is localized on the porphyrin ring, while in the proteins it is partly delocalized onto the proximal ligand. Thus, the proximal axial ligand of iron participates indirectly in the oxidation reactions catalyzed by the enzymes. Possible roles of the axial ligand in the catalytic mechanism of these heme-based enzymes are discussed.

Hydroxylation of benzene and fluorobenzene catalyzed by an Fe(IV)-oxo porphyrin cation

Hydroxylation of benzene and fluorobenzene catalyzed by an Fe(IV)-oxo porphyrin cation

Resonance Raman spectra of highly oxidized metalloporphyrins and heme proteins

Studies of resonance Raman (RR) spectra of highly oxidized metalloporphyrins and heme proteins in the past decade are surveyed comprehensively. Following the introduction this article consists of two main sections. In Section 2 the Fe IV=O stretching ( v(Fe IV=O)) vibrations of ferryloxo neutral and /Gv cation radical porphyrins and their porphyrin in-plane modes are discussed and the characters of the Fe IV=O bond and environmental effects on it are elucidated. For porphyrin π cation radicals, the RR spectral differences between the a 1u and a 2u radicals are interpreted in relation to the electronic properties of those orbitals for divalent metalloporphyrins as well as iron porphyrins. Some changes in vibrational characters on oxidation of the porphyrin ring are noted on the basis of isotopic substitution data. Studies of environmental effects on porphyrin π cation radicals permit one to deduce factors for determination of radical types. Current RR studies of nitrido iron and N-oxide iron porphyrins and other metal oxo porphyrins with M IV, M V and M VI ions are also covered. In Section 3 the present state of RR studies of reaction intermediates of heme enzymes containing ferryloxo neutral and π cation radical porphyrins is summarized, and discussion is focused on the v(Fe IV=O) RR bands. Attention is paid to compound I of horseradish peroxidase for which complete historical vicissitudes of observed RR spectra are pursued. The most recent results from RR studies of reaction intermediates of cytochrome c oxidase with the Fe III-O-O-H and Fe IV=O hemes are explained in detail. Finally RR spectra of reaction intermediates of iron-chlorin containing enzymes as well as those of catalase and thiolate-ligated heme enzymes are reviewed.

Electroanalytical study of the activation of dioxygen in acetonitrile solution by manganese porphyrin films deposited onto carbon electrodes

Electrochemical analysis of the activation of dioxygen in aprotic solutions (acetonitrile) by manganese porphyrin polymer films was investigated by rotating disk electrode voltammetry. In the presence of a benzoic anhydride electrophile, the electrocatalytic reduction of O 2 occurs by a process postulated to involve a high-valent manganese—oxo porphyrin according to a same scheme already described for the metalloporphyrin dissolved in solution. In addition, this analysis shows that thin polypyrrole—manganese porphyrin films do not induce a limitation due to the diffusion of O 2 and other reagents through the polymer during the electrocatalytical activation of dioxygen.

Mechanistic study of decomposition of cyclohexyl hydroperoxide catalysed by manganese(III) tetraarylporphyrins

AbstractThe reaction between manganese(III) tetraarylporphyrins and cyclohexyl hydroperoxide has been investigated. Since pyridine increases the decomposition rate of cyclohexyl hydroperoxide, all experiments were performed in the presence of pyridine. Experiments with 2,6‐di‐tert‐butylpyridine showed that pyridine increases the reaction rate by ligation to the manganese porphyrin as well as by acting as a base. Cyclohexyl hydroperoxide is decomposed into cyclohexanol and cyclohexanone. Since neither 3,3,5,5‐tetramethylcyclohexanol nor cyclohexanol‐d12 are oxidized under these reaction conditions, cyclohexanone is formed directly from the peroxide and not by oxidation of the alcohol. During the reaction, a manganese(V)oxo porphyrin complex is formed. This complex may react with (i) the peroxide under formation of cyclohexanol and molecular oxygen, (ii) the solvent cyclohexane, or (iii) manganese(III) porphyrin. The latter reaction leads to destruction of the catalyst. This destruction is prevented by introduction of bulky groups on the ortho positions of the phenyl. The scission of the hydroperoxide is suggested to be heterolytic. It is also base‐catalysed. The rate‐determining step in the decomposition of cyclohexyl hydroperoxide is scission of the oxygenoxygen bond of the manganese peroxyl porphyrin complex. A mechanism in line with the kinetic data is proposed.

Mechanistic aspects of the oxidation of phenothiazine derivatives by methemoglobin in the presence of hydrogen peroxide

Mechanistic aspects of the reaction of hydrogen peroxide with methemoglobin with respect to phenothiazine oxidation have been studied. Three phenothiazines, methoxy- (MoPZ), chlor- (CPZ) and methoxycarbonylpromazine (MaPZ), have been used. These phenothiazines differ only in substitution at the 2-position, which contributes substantially to the electron-donating properties of these compounds. Reaction with hydrogen peroxide oxidizes methemoglobin to ferrylhemoglobin, which contains iron(IV)-oxo porphyrin moiety and a protein radical. The phenothiazines are oxidized by ferrylhemoglobin in the presence of H 2O 2 mainly to their sulfoxides, with a radical cation as intermediate. The conversion rates (MoPZ > CPZ > MaPZ) decrease with the electron-withdrawing ability of the 2-substituent, as indicated by Hammett σ para values. Hydrogen peroxide consumption during the reaction is similar for the three phenothiazines. Denaturation reactions that occur upon exposure of methemoglobin to hydrogen peroxide have been investigated. For this heme-protein cross-linking was studied by means of heme retention by the protein after methyl ethyl ketone extraction. Furthermore, oxygen consumption during the reaction was assayed, which indicates formation of protein-peroxy radicals. The extent of both heme-protein cross-linking and oxygen consumption is decreased by phenothiazines in the same order as the phenothiazine conversion rate. CPZ sulfoxide is not converted by methemoglobin in the presence of hydrogen peroxide, and CPZ sulfoxide shows no effect on heme-protein cross-linking and oxygen consumption. The results are explained by electron transfer from phenothiazine to the protein radical. Stronger electron donors (MoPZ > CPZ > MaPZ) are converted faster and by reducing the protein radical they better protect hemoglobin against denaturation. A catalytic cycle, that takes into account our observation and the existing knowledge of hemoglobin oxidation states, is presented.

Factors affecting the iron-oxygen vibrations of ferrous oxy and ferryl oxo heme proteins and model compounds

Resonance Raman (RR) and UV-visible absorption spectra of various imidazole-ligated ferrous oxy (Fe II― O 2 ) and ferryl oxo (Fe IV =O) porphyrins are presented. Because physiologically relevant porphyrins have been used in this study, these measurements provide a basis to identify protein-induced changes in the iron-oxygen vibrations, as well as in the structure-sensitive macrocycle vibrations and in the optical absorption spectra, of heme enzyme intermediates

ChemInform Abstract: Electrochemical Generation of Iron(IV)‐Oxo Porphyrins and Iron(IV)‐Oxo Porphyrin π Cation Radicals.

AbstractFe(III) porphyrin complexes with weakly basic ligands (Cl‐ or ClO4‐) in the first electrochemical one‐electron oxidation yield Fe(III) porphyrin π‐cation radicals.