Cytochrome P450 models

S.3 Cytochrome P450 Model Compounds Functional. Ferric-peroxo species are part of the cytochrome P450 catalytic cycle as discussed previously in Section 7.4.4. For instance, these ferric-peroxo moieties are known to act as nucleophiles attacking aldehydic carbon atoms in oxidative deformylations to produce aromatic species.An example of this work, establishing the nucleophilic nature of [(porphyrin)Fe (02)] complexes, was achieved for alkene epoxidation reactions by J. S. Valentine and co-workers. The electron-deficient compound menadione (see Figure 7.18) yielded menadione epoxide when reacted with a [(porphyrin)Fe X02)] complex. 

Figure 7.22 Cytochrome P450 model compound reaction profile consistent with a multi-step catalytic mechanism. (Adapted with permission from Schemes 7 and 8 of reference 68. Copyright 1997, Society of Biological Inorganic Chemistry.)...

Figure 17 (a) Crown ether based cytochrome P450 model (b) alcohol dehydrogenase model (c) proposed transition state in carbonyl group reduction by 1,4-dihydropyridine-containing crown ethers... 

The mechanism of the epoxidation of alkenes by the cytochrome P450 model, sodium hypochlorite-manganese(III) tetraarylporphyrins, involves rate-determining formation of an active species 234 from a hypochlorite-manganese complex 233 (Scheme 6) pyridine or imidazole derivatives, as axial ligands, accelerate this step by electron donation, although the imidazoles are destroyed under the reaction conditions368. 

Bathelt CM, L Ridder, AJ Mulholland, JN Harvey (2003) Aromatic hydroxylation by cytochrome P450 Model calculations of mechanism and substituent effects. J. Am. Chem. Soc. 125 (49) 15004-15005... 

Synthetic metalloporphyrins as biomimetic catalysts (cytochrome P450 models) in the oxidative activation of drugs 04MI33. 

Higuchi, T. and M. Hirobe (1996). Four recent studies in cytochrome P450 modelings A stable iron porphyrin coordinated by a thiolate ligand a robust ruthenium porphyrin-pyridine N-oxide derivatives system polypeptide-bound iron porphyrin application to drug metabolism smdies. J. Mol. Catal A Chem. 113, 403 22. 

Chottard, G., M. Schappacher, L. Ricard, and R. Weiss (1984). Resonance Raman spectra of iron(l 1) cytochrome P450 model complexes Influence of the thiolate ligand. Inorg. Chem. 23, 4557 561. 

Gleeson and co-workers used continuous regression methods to build Cytochrome-P450 models. In assessing the performance in an external prediction set, they used the RMSE of the fitted model to define an exclusion zone around the cut-off value where misclassification would be more likely, as illustrated in Figure 9.4. ... 

The use of mejo-(o-aminophenyl)triphenylporphyrin 57 to prepare a series of alkyl and aryl mercaptan-tail porphyrins as cytochrome P450 models has been described in Sect. 3.B. A similar series of compounds has been prepared by acylation of the tripivalamide-p-aminophenylporphyrin 147 to give the alkyl mercaptan tailed picket-fence porphyrins 154 (Scheme 45) . A similar compound 155 with an appended thioether chain has also been prepared and is reportedly capable of reversibly binding dioxygen ... 

Battersby et al. have prepared a series of strapped porphyrins bearing variously substituted pyridine ligands Reaction of the porphyrin bis-acid chloride 180 with the corresponding pyridine diol 207 gave the ester-linked pyridine straps 208 a-c in up to 38% yield (Scheme 62). The molecular structure of a crystalline side-product of these syntheses is shown in Fig. 11 . A cytochrome P450 model was prepared similarly (Scheme 63). A suitably functionalized diol 211 was reacted under high dilution with the bis-acid chloride of mesoporphyrin II (180) to give the strapped porphyrin 212 in 25%... 

Busch et al. on their search for a cytochrome P450 model useful for the selective oxidation of alkanes investigated the macrobicyclic nickel(II) complex 71 with respect to its inclusion capacity for aliphatic alcohols and phenols. A shift of the host protons in the course of the guest addition (e.g. 1-butanol, phenol) in D O the formation of in-... 

Cytochrome P450 is one of nature s oxidative workhorses, and it is involved in a wide variety of biological reactions, one of the most important being the detoxification of foreign bodies within the liver. A wide variety of approaches was developed to design and construct synthetic model systems of the cytochrome P450 family.They vary from the earlier mentioned "capped" and "picnic basket" porphyrins, over supramolecular cytochrome P450 models, to dendritic porphyrins. ... 

Lu, W.Y., J.F. Bartoli, P. Battioni, and D. Mansuy (1992). Selective oxygenation of hydrocarbons and sulfoxidation of thioethers by dioxygen with a Mn-porphyrin-based cytochrome P450 model system using Zn as electron-donor. New J. Chem. 16, 621-628. 

More recently, research concerning catalytic oxidation reactions has emerged on one side from bioinorganic chemistry with cytochrome P450 models and non-por-phyrinic methane mono-oxygenase models, and on the other side, from organic chemistry with asymmetric epoxidation and dihydroxylation. 

A review has been written on the topic of synthetic active-site analogues of heme-thiolate proteins. As well as cytochrome P450, models for chloro-peroxidase are dicussed. Alkanethiolate-coordinated iron porphyrins and their dioxygen adducts have been synthesized and characterized as P450 models. ... 

---