Electronic ground states of iron porphyrin and of the first species in the catalytic reaction cycle of cytochrome P450s

Electronic structures of iron(II) and iron(III) porphyrins are studied with density functional theory (DFT) using the GGA exchange functional OPTX in combination with the correlation functional PBE (OPBE) and with the correlation functional Perdew (OPerdew) together with a triple zeta-type basis set. These functionals, known for accurately predicting the spin ground state of iron complexes, are evaluated against other functionals for their performance in calculating relative energies for the various electronic states of both the iron porphyrins. The calculated energy orderings are triplet < quintet < singlet for the iron(II) porphyrin and quartet < sextet < doublet for the iron(III) porphyrin cation. Complexation by a thiolate ion (SH-) changes the preferred ground state for both species to high spin. This thiolate complex is used as a mimic for the cytochrome P450s active site to model the first step of the catalytic cycle of this enzyme. This first step is believed to concern the removal of an axial oxygen donating ligand from the hexacoordinated aqua-thiolate-porphyrin-iron(III) resting state. The DFT results suggest that this is not a free water molecule, because of its repulsive nature, but that it has instead hydroxy anion character. These calculations are in line with the experimentally observed change in the spin state from low to high spin upon this removal of the axial hydroxo ligand by binding of the substrate in the heme pocket of cytochrome P450.     

Fast nitroxyl trapping by ferric porphyrins

Iron(II) porphyrin nitrosyl complexes are obtained in high yields from the reaction of iron(III) porphyrins with the nitroxyl donors sodium trioxodinitrate and toluensulfohydroxamic acid. The reaction was found to proceed both in organic solvents and in aqueous media from iron(III) (meso-tetraphenyl) porphyrinate ([FeIII(TPP)]+) and iron(III) meso-tetrakis (4-sulfonatophenyl) porphyrinate ([FeIII(TPPS)]3-) or iron(III) protoporphyrin IX, respectively. The kinetic rate constant for the reaction of ([FeIII(TPPS)]3-) with sodium trioxodinitrate (kon) was estimated to be 1.00 +/- 0.04 x 107 M-1 s-1. As well as resulting in a versatile method for obtaining ferrous nitrosyl porphyrins, the reaction points at ferric porphyrins as efficient nitroxyl traps and provides a tool to model nitroxyl reactivity toward hemeproteins.     

The reaction of porphyrins with organolithium reagents

Porphyrins react readily with organolithium reagents, preferentially in the meso positions. The overall reaction is a nucleophilic substitution and proceeds via initial reaction of the organic nucleophile with a meso carbon yielding an anionic species which is hydrolyzed to a porphodimethene (5,15-dihydroporphyrin), formally constituting an addition reaction to two Cm positions. Subsequent oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) yields meso-substituted porphyrins. The reaction is highly versatile as it is accomplished in high, often quantitative yields with various alkyl or aryl lithium reagents. In addition, LiR can be used for reaction with a variety of metal complexes (best with NiII, but also with ZnII, CuII, and CoII) and most useful with free base porphyrins. Similarly beneficial this reaction can be used in sequence for the introduction of 1, 2, 3, or 4 (different) meso substituents giving for the first time an entry into any desired meso-substituted porphyrin. If meso-substituted porphyrins are used, reaction with LiR can be used for either the preparation of phlorins (already known reaction), porphodimethenes (5,15-dihydroporphyrins, including those with exocyclic double bonds, for example, 5(1),5(2)-didehydroporphyrins) or chlorins (2,3-dihydroporphyrins) depending on the substituent type in the reactant porphyrins. Thus, this reaction presents a generally applicable method for the facile and versatile functionalization of porphyrins.     

Application of low-temperature rapid-scan techniques in the elucidation of inorganic reaction mechanisms

Reactions that occur too rapidly to be monitored by rapid reaction methods at temperatures at or close to ambient can be investigated kinetically by retarding their reaction rates employing very low temperatures. A selection of reactions studied by this approach (low-temperature stopped-flow spectrophotometry) is reported. Details of the reaction mechanisms have been revealed for peroxide activation involving iron(III) porphyrins and cytochrome P450, superoxide activation involving manganese(II) complexes and iron porphyrin complexes, and dioxygen activation and binding by model mono-, and dinuclear copper(I) complexes and dioxygen activation at mono-, and dinuclear non-heme iron complexes. A final section covers progress in unravelling the mechanism of carbon–hydrogen bond activation by platinum complexes.     

位阻型金属卟啉的合成及其催化烷烃基化的反应

本文用平衡法制备了中位-四(3,5-二叔丁基-4-甲氧基等基)卟啉(T~D~T~B~M~OPP), 并制备了该卟啉的铁、锰、钴、锌、铜、镍的金属配合物。经红外光谱、电子光谱、核磁共振谱, 元素分析等确认了这些均未见报道的金属卟啉。考察了在温和条件下, 以T~D~T~B~M~O PP Fe^III C和T~D~T~B~M~O PP Mn^III Cl为了催化剂, PhIo为氧化剂, 在CH~2Cl~2中氧化n-C~6H~1~4的反应, 并将结果与别的催化剂进行了比较。     

First observation in the gas phase of the ultrafast electronic relaxation pathways of the S(2) states of heme and hemin

The time evolution of electronically excited heme (iron II protoporphyrin IX, [Fe(II) PP]) and its associated salt hemin (iron III protoporphyrin IX chloride, [Fe(III) PP-Cl]), has been investigated for the first time in the gas phase by femtosecond pump-probe spectroscopy. The porphyrins were excited at 400 nm in the S(2) state (Soret band) and their relaxation dynamics was probed by multiphoton ionization at 800 nm. This time evolution was compared with that of the excited state of zinc protoporphyrin IX [Zn PP] whose S(2) excited state likely decays to the long lived S(1) state through a conical intersection, in less than 100 fs. Instead, for [Fe(II) PP] and [Fe(III) PP-Cl], the key relaxation step from S(2) is interpreted as an ultrafast charge transfer from the porphyrin excited orbital π* to a vacant d orbital on the iron atom (ligand to metal charge transfer, LMCT). This intermediate LMCT state then relaxes to the ground state within 250 fs. Through this work a new, serendipitous, preparation step was found for Fe(II) porphyrins, in the gas phase.     

Mechanistic studies on the nucleophilic reaction of porphyrins with organolithium reagents.

Porphyrins react readily with organolithium reagents under substitution of free meso positions. As this method has proven to be very versatile for the preparation of a wide range of meso substituted porphyrins, a mechanistic study of the reaction was undertaken using 5,15-diaryl- and dialkyl substituted porphyrins, 2,3,7,8,12,13,17,18-octaethylporphyrin, and the respective nickel(II) complexes. A combination of deuteration experiments, electronic absorption spectroscopy of the reactive intermediates, trapping of intermediates with organic electrophiles, and reaction at different pH values showed significant differences in the reaction pathways of free base porphyrins and metalloporphyrins. In both cases the reaction proceeds initially under formation of phlorin like intermediates which are stable in water. For the Ni(II)phlorins a mesomeric carbanionic form with a highly distorted structure exists that can react as a nucleophile with electrophiles such as RI, H+, or D+. In the latter case a protonation-deprotonation equilibrium involving porphodimethen intermediates has to be assumed. Free base phlorins do not react as nucleophiles but can undergo H/D exchange reactions in strongly acidic media.     

Electronic structure of some substituted iron(II) porphyrins. Are they intermediate or high spin?

The electronic structure of some substituted, four-coordinate iron(II) porphyrins has been investigated with DFT methods. These systems include iron tetraphenylporphine (FeTPP), iron octamethyltetrabenzporphine (FeOTBP), iron tetra(alpha,alpha,alpha,alpha-orthopivalamide)phenylporphine (FeTpivPP, also called "picket fence" porphyrin), halogenated iron porphyrins (FeTPPXn, X=F, Cl; n=20, 28), and iron octaethylporphine (FeOEP). A number of density functionals were used in the calculations. Different from the popular, intermediate-spin FeTPP, the ground states of FeOTBP, FeTPPCl28, and FeTPPF20betaCl8 are predicted to be high spin. The calculated result for FeOTBP is in agreement with the early experimental measurement, thereby changing the previous conclusion drawn from the calculations with only the BP functional (J. Chem. Phys. 2002, 116, 3635). But FeTpivPP might have an intermediate-spin ground state, a conclusion that is different from the "experimental" one. With a notably expanded Fe-N bond length, FeOEP might exist as an admixed-spin (S=1, 2) state. We also calculated the electron affinities (EAs) for the various iron porphyrins and compared them to experiment. On the basis of the calculated trends in the EAs and in the orbital energies, the experimental EAs for FeTpivPP, FeTPPF20, and FeTPPCl28 may be too small by 0.4-0.5 eV.     

Exploration of the reaction of potassium organotrifluoroborates with porphyrins

A general method that uses potassium organotrifluoroborates in the Suzuki-Miyaura cross-coupling reaction with ring-brominated porphyrins has been investigated. The reaction conditions tolerate various functional groups and are applicable to the meso- and β-position as well as to aryl- and alkyl-substituted porphyrins. Depending on the nature of the potassium organotrifluoroborate, the coupling products can be obtained in yields of up to 75%.     

Synthesis, characterization and spectral properties of substituted tetraphenylporphyrin iron chloride complexes

A series of substituted tetraphenylporphyrin iron chloride complexes [RTPPFe(III)Cl, R=o/p-NO?, o/p-Cl, H, o/p-CH?, o/p-OCH?] were synthesized by a novel universal mixed-solvent method and the spectral properties of free base porphyrins and iron porphyrin compounds were compared with each other. The experimental results showed that the one-pot mixed solvent method was superior to the two-step method in the yields, reaction time and workup of reaction mixtures for the synthesis of iron porphyrin compounds. The highest yields (28.7%-40.4%) of RTPPFe(III)Cl were obtained in the mixed solvents propionic acid, glacial acetic acid and m-nitrotoluene under reflux for 2 h. A detailed analysis of ultraviolet-visible (UV-vis), infrared (IR) and far-infrared (FIR) spectra suggested the transformation from free base porphyrins to iron porphyrins. The red shift of the Soret band in ultraviolet-visible spectra due to the presence of p-nitrophenyl substituents and the blue shift of Fe-Cl bond of TPPFeCl in far-infrared spectra were further explained by the electron transfer and molecular planarity in the porphyrin ring.     

A Non-Heme Iron(III) Complex with Porphyrin-like Properties That Catalyzes Asymmetric Epoxidation

In this report, we describe an iron(III) complex containing a carbazole-based tridentate ligand that catalyzes highly enantioselective asymmetric epoxidation of (E)-alkenes at room temperature. The non-heme iron(III) complex has a five-coordinated trigonal-bipyramidal structure, and its two-electron oxidized state has the similar electronic structure as that of iron porphyrins.     

Efficient excited energy transfer reaction in clay/porphyrin complex toward an artificial light-harvesting system

The quantitative excited energy transfer reaction between cationic porphyrins on an anionic clay surface was successfully achieved. The efficiency reached up to ca. 100% owing to the "Size-Matching Rule" as described in the text. It was revealed that the important factors for the efficient energy transfer reaction are (i) suppression of the self-quenching between adjacent dyes, and (ii) suppression of the segregated adsorption structure of two kinds of dyes on the clay surface. By examining many different kinds of porphyrins, we found that tetrakis(1-methylpyridinium-3-yl) porphyrin (m-TMPyP) and tetrakis(1-methylpyridinium-4-yl) porphyrin (p-TMPyP) are the suitable porphyrins to accomplish a quantitative energy transfer reaction. These findings indicate that the clay/porphyrin complexes are promising and prospective candidates to be used for construction of an efficient artificial light-harvesting system.     

First insight into catalytic activity of anionic iron porphyrins immobilized on exfoliated layered double hydroxides

Mg-Al layered double hydroxide (LDH) intercalated with glycinate anions was synthesized through co-precipitation and exfoliated in formamide and the single-layer suspension was reacted with aqueous iron porphyrin solutions (Fe(TDFSPP) and Fe(TCFSPP)). The obtained materials were characterized by X-ray powder diffraction, UV-vis, and electron paramagnetic resonance and investigated in the oxidation reaction of cyclooctene and cyclohexane using iodosylbenzene as oxidant. The iron porphyrin seems to be immobilized at the surface of the glycinate intercalated LDH. The catalytic activities obtained in heterogeneous media for iron porphyrin, Fe(TDFSPP), was superior to the results obtained under homogeneous conditions, but the opposite effect was observed on the Fe(TCFSPP), indicating that, instead of the structural similarity of both iron porphyrins (second-generation porphyrins), the immobilization of each one produced different catalysts. The best catalytic activity of the Fe(TDFSPP)/Gly-LDH, compared to Fe(TCFSPP)/Gly-LDH, can be explained by the easy access of the oxidant and the substrate to the catalytic sites in the former, probably located at the surface of the layered double hydroxide pillared with glycinate anions. A model for the immobilization and a mechanism for the oxidation reaction will be discussed.     

Multiple active intermediates in oxidation reaction catalyzed by synthetic heme-thiolate complex relevant to cytochrome p450

We have studied oxidation reactions using a synthetic heme-thiolate (SR complex) in order to ascertain the contributions of multiple intermediates derived from heme-thiolate to the oxygen atom transfer reaction to substrate. First, degradation of peroxyphenylacetic acid (PPAA) was examined in the presence of various substrates. The O-O bond cleavage mode of PPAA was clearly dependent on the reactivity of the substrate, and an easily oxidizable substrate enhanced heterolytic O-O bond cleavage. Second, competitive oxidations of cyclooctane and cyclooctene were carried out with various peroxybenzoic acids containing a series of substituents at the para-position as an oxygen source. The ratios of alkane hydroxylation rate/alkene epoxidation rate were dependent on the nature of the para-substituent of the oxidant. We conclude that substrate and oxidant interact with each other during the oxygen atom transfer reaction, that is, oxidation reaction occurs before O-O bond cleavage, even in the reaction catalyzed by heme-thiolate, which is considered to promote O-O bond cleavage. The results of an (18)O-incorporation study that is frequently performed to determine the active intermediates derived from iron porphyrins were consistent with this conclusion.     

金属卟啉催化烯烃环氧化及反应机理研究*

本文就铁卟啉及锰卟啉模拟酶体系近年来在催化烯烃环氧化反应机理方面的最新研究成果进行了详细阐述。均相催化剂固载化技术的应用,使金属卟啉配合物担载于无机载体上克服了卟啉的二聚、催化剂再生等难题,有力地推动了金属卟啉配合物应用研究的发展。     

Iron porphyrins anchored to a thermosensitive polymeric core-shell nanosphere as a thermotropic catalyst

A thermosensitive nanocatalyst was prepared in the reaction of water-soluble iron(III) porphyrins and thermosensitive polymeric nanospheres with a core-shell structure; its catalytic activity in cyclohexene oxidation by iodosylbenzene was dependent markedly on reaction temperatures in aqueous solution.     

5,15-二(对-取代苯基)八烷基卟啉及其金属配合物的合成

本文报道了五种5,15-二(对-取代苯基)-2,8,12,18-四乙基-3,7,13,17-四甲基卟啉(Ⅱa—Ⅱe)和五种5,15-二(对-取代苯基)-2,3,7,8,12,13,17,18-八甲基卟啉(Ⅰa—Ⅰe)以及它们的铜、铁、镍金属配合物的合成。这些化合物的结构均经元素分析、UV、~1HNMR和MS鉴定。芳环上不同取代基对卟啉成环反应有一定影响,拉电子基团有利于反应。其顺序如下:NO_2>H>CH_3>OCH_3>N(CH_3)_2。     

Iron(II) complexes with amide-containing macrocycles as non-heme porphyrin analogues

Iron(II) complexes of macrocyclic pentadendate ligands 3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene-2,13-dione (H2pydioneN5) and 16-chloro-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene-2,13-dione (H2pyCldioneN5) were synthesized and fully characterized. Complexes with one or two deprotonated amide groups of H2pydione were both isolated. In the former case the metal ion has a distorted octahedral coordination sphere; in the latter case the complex adopts a pentagonal-bipyramidal geometry. NMR experiments show that the protonation state of the ligand is preserved in a dimethyl sulfoxide (DMSO) solution. The complexes maintain a high-spin state even at low temperatures. Detailed kinetic studies of oxygenation of the iron(II) complexes showed that the deprotonation state of the complex has a profound effect on the reactivity with dioxygen. Oxygenation of the dideprotonated complex of iron(II), Fe(pydioneN5), in aprotic solvents proceeds via a path that is analogous to that of iron(II) porphyrins: via iron(III) superoxo and diiron(III) peroxo species, as evidenced by the spectral changes during the reaction, which is second-order in the concentration of the iron(II) complex, and with an inverse dependence of the reaction rate on the concentration of dioxygen. The final products of oxygenation are crystallographically characterized iron(III) mu-oxo dimers. We have also found that the presence of 1-methylimidazole stabilizes the diiron peroxo intermediate. The reaction of Fe(pydioneN5) with dioxygen in methanol is distinctly different under the same conditions. The reaction is first-order in both iron(II) complex and dioxygen, and no intermediate is spectroscopically observed. Similar behavior was observed for the monodeprotonated complex Fe(HpydioneN5)(Cl). The presence of an accessible proton either from the solvent (reactions in methanol) or from the complex itself (in Fe(HpydioneN5)(Cl)) proves sufficient to alter the oxygenation pathway in these macrocyclic systems, which is reminiscent of the properties of iron(II) porphyrin complexes. The new amidopyridine macrocycles can be considered as new members of the "expanded porphyrin analogue" family. The expansion of the cavity provides control over the spin state and availability of protons. These macrocyclic systems also allow for easy synthetic modifications, paving the way to new, versatile metal complexes.     

Effect of solvent nature on the reaction of metallic iron with benzoic acid in a bead mill

Results of an experimental study of the influence exerted by the solvent nature on the reaction rate, achieved degree of acid expenditure, selectivity with respect to salts of iron(II) and (III), and phase state of the reaction mixture in a single-stage reaction of iron with benzoic acid and atmospheric oxygen in the presence of a stimulating iodine additive are presented.     

Mechanism of cyclohexane oxidation by molecular oxygen in the biomimetic iron porphyrin system with proton and electron donors: I. A radical pathway

The formation of cyclohexyl hydroperoxide during cyclohexane oxidation by air oxygen in a biomimetic iron porphyrin system with proton (AcOH) and electron (Zn) donors and with or without an electron carrier (methylviologen (MV)) in an acetonitrile solution is detected by gas-liquid chromatography. The kinetics of C₆H₁₁OOH decomposition in this system catalyzed by iron porphyrins with various substituents in the phenyl rings is studied, and the rate constants of this process are determined. A kinetic scheme of cyclohexane oxidation is proposed. The contribution of the radical pathway to the reaction product formation is quantitatively estimated in the pseudo-steady-state approximation. For all iron porphyrins under investigation (FeTPP, FeTDCPP, and FeTpivPP), the fraction of the products formed via the radical pathway is smaller than 20%.