Model systems for cytochrome

V.B. Model Systems for Cytochrome P-450 Using Single Oxygen Atom Donors... 

Gunter and coworkers have synthesized a lateral macrobicyclic molecule 197 where a phorphyrin ring is capped by a bridging unit which contains a pyridino subunit. This model system for cytochrome c oxidase is in fact a heterodinuclear complex with iron(III) complexed to the porphyrin unit and copper(II) complexed to the lateral pyridino bridge. A series of these complexes have been made with... 

Figure 9 Formulas of polyhalogenated porphyrins used in model systems for cytochrome P450...

P. Inchley, J.R. Lindsay Smith and R.J. Lower, Model systems for cytochrome... 

J.R. Lindsay Smith and P.R. Sleath, Model Systems for cytochrome P450 dependent... 

A number of studies have been reported in which a metal atom catalyzes the oxidation of alkenes by PhIO or its derivatives. Three studies have employed iron or manganese model systems for cytochrome P-450 in the oxidation of alkenes. " " [Ru(III) (salen)(X)(Y)] catalyze the oxidation of alkenes by PhIO at room temperature.Similarly, ruthenium(II) complexes of bidentate phosphines may be utilized to promote the epoxidation of alkenes in the presence of iodosylbenzene and in low coordinating media. [Ni(cyclam)] promotes the oxidation of... 

Figure 9 Bimetallic model system for cytochrome P-450 composed of a manganese porphyrin and a rhodium(III) bipyridine complex anchored to a vesicle bilayer.

Numerous model systems for cytochrome P-450 have focussed upon the use of porphyrin complexes of chromium, manganese and iron in the presence of O2, peracids, hydroperoxides, AT-oxides or iodosylarenes as terminal oxidant [5, 6]. It is generally agreed that these systems generate a high valent metal-oxo species which participates in a rebound mechanism to shuttle an oxygen atom to a hydrocarbon... 

An important model system for electron transfer studies is the electron carrier cytochrome c (Cyt c). Its redox center is a heme, coordinated by a histidine and... 

Cytochromes are electron-transfer proteins having one or several haem groups. Cytochrome c binds to the protein by one or, more commonly two, thioether bonds involving sulphydryl groups of cysteine residues. The fifth haem iron ligand is always provided by a histidine residue. Cytochrome c has been proved to be a useful model system for studying the relationship between protein structure and thermostability due to the availability of its three-dimensional structure from a wide variety of organisms, both mesophiles and thermophiles. 

An iron porphyrin is the prosthetic group in the oxygen transport and storage proteins, hemoglobin and myoglobin. Consequently there has been much interest in porphyrin complexes, especially of first row transition metals, as model systems for oxygen transport and storage. Much interest has also been shown in metal porphyrins as models for oxidases, in particular cytochrome P-450. 

By H NMR monitoring of the oxidation of benzene oxide-oxepine with dimethyldioxirane (DMDO), a significant by-product, oxepine 4,5-dioxide, was identified <1997CRT1314>. This fact supports the hypothesis that the route from oxepine to muconaldehyde proceeds via oxepine 2,3-oxide with a minor pathway leading to symmetrical oxepine 4,5-oxide. The DMDO oxidations provide model systems for the cytochrome P450-dependent metabolism of benzene and atmospheric photooxidation of benzenoid hydrocarbons. 

There are a number of factors which make flavocytochrome b2 an ideal model system for studying both intra- and inter-molecular electron transfer. Reasons include (i) the fact that it has been expressed at a high level in E. coli (Black et al., 1989) and is soluble and easily obtained (ii) crystal structures of the native (Xia and Mathews, 1990) and recombinant (Tegoni and Cambillau, 1994) enzymes are available (iii) a hypothetical structure for the flavocytochrome 4 2 cytochrome c complex has been proposed (Short et al., 1998) (iv) many mutant forms of the enzyme have been constructed (v) there is a wealth of data on the mechanism of action of the enzyme (Chapman et ah, 1991 Lederer, 1991). 

Table 14 Monooxygenation and dehydrogenation of organic substrates via a model system for the cytochrome P-450 monooxyge-nase/reductase enzymes ...

J. R. Lindsay Smith, D. N. Mortimer, The oxidation of organic compounds with lodosylbenzene catalysed by tetra(4-N-methylpyridyl)porphyrinatoiron(III) pentacation A polar model system for the cytochrome P450 dependent mono-oxygenases, J. Chem. Soc. Chem. Commun. (1985) 410. 

Table 6-4 Mono-oxygenation and Dehydrogenation of Organic Substrates via a Model System for the Cytochrome P-450 Mono-oxygenase/Reductase Enzymes"...

Further investigations of heme peptides from cytochrome c were carried out by both ORD and CD measurements (227, 163, 228, 202). The aggregated hemepeptides were considered as model systems for interactions between hemes in biological systems. By analysis of light-absorption and CD data, exciton interactions between the Soret transitions in aggregated hemes were estimated. Under the conditions used,... 

These reactivity studies, and the observation of the peroxide shunt described above, indicate that Fe (P )(0) + or Fe (P )(0) is the most likely eandi-date for active oxygen. These two formulations are, of course, isoelectronie, and it is tempting to conclude that the latter is the more likely formulation of the enzymatic intermediate. However, it is important to remember that the model systems lack the axial cysteinyl ligand present in cytochrome P-450. The effect of the relatively easily oxidized sulfur ligand on the electron distribution within that intermediate is not known, since model systems for high-valent iron-oxo complexes containing axial thiolate ligands have not been synthesized. 

For non-activated olefins like styrol, cyclohexene and cyclooctene Chauhan et al. investigated iron(iii)porpyhrine systems in combination with H2O2 as a suitable epoxidation system [153]. The metaUoporphyrines were used as model catalysts for cytochrome P450 and were immobilized in [BMIM]Br. The yields were found to depend on the applied olefin and varied from 42% for cyclohexene, 74% for styrene, to 81% for cyclooctene. Recycling was possible for the epoxidation of styrene in 5 runs under biphasic reaction conditions and the yield decreased from 74% for the first run to 62% for the fifth run. 

Synthetic metalloporphyrins have received a lot of recent attention as mimics of numerous enzymes. In addition, 10 models have been developed for peroxidases and particularly, ligninases. Metalloporphyrins have also found utility as model systems for studies of the oxidative metabolism of drugs.A detailed study of the metabolism of lidocaine has been reported, as have preliminary studies on the use of metalloporphyrins as chemical mimics of cytochrome P450 systems (Scheme 29.24). ... 

D.W Urry and J.W Pettegrew, Model Systems for Interacting Heme Moieties. II. The Ferri-heme Octapeptide of Cytochrome. J. Am. Chem. Soc., 89,5276-5283,1967. 

Iron porphyrin systems containing reducing agents serve as model sytems for cytochrom P-450. The mechanism given in Scheme 5 has been proposed for the biomimetic catalyst system Fe(TPP)Cl/Zn(Hg)/methyl viologen/Ac O in acetonitrile for the hydroxylation of cyclohexane... 

In electrochemical systems, on the other hand, electrodes act as both electron acceptors and electron donors, and are considered a simple model system for mimicking a charged interface of the physiological binding domain. The heterogeneous ET reactions between electrodes and various ET proteins in solutions have been extensively studied, as described in previous chapters. The electrode reactions of cytochrome c at mercury, platinum, silver, and gold electrodes have been reported to be irreversible. On the other hand, the electrode reactions of cytochromes C3 (cyt. C3) have... 

Araki K, Toma HE (2009) Supramolecular porphyrin model compounds for cytochrome p-450, cytochrome-c oxidase and photosynthetic systems. In Merce ALR, Felcman J, Recio MAE (eds) Molecular and supramolecular bioinorganic chemistry applications in medical sciences. Nova Science Publishers, New York, pp 83-136... 

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