Peroxidase model complexes

Nicolis S, Casella L, Roncone R, Dallacosta C, Monzani E (2007) Heme-peptide complexes as peroxidase models. C R Chimie 10 380-391... 

Model complexes of peroxidase were used as catalysts for the oxidative polymerization of phenols. Hematin, a hydroxyferriprotoporphyrin, catalyzed the polymerization of />ethylphenol in an aqueous DMF.63 Iron—A/,A/ -ethylenebis(salicylideneamine) (Fe—salen) showed high catalytic activity for oxidative polymerization of various phenols.64 The first synthesis of crystalline fluorinated PPO was achieved by the Fe—salen-catalyzed polymerization of 2,6-difluorophenol. Cardanol was polymerized by Fe— salen to give a cross-linkable polyphenol in high yields. 

Early peroxidase models were based on simple metal complexes or modified hemin derivatives. Anionic metalloporphyrins adsorbed on ion-exchange resins have an efficient peroxidase activity. 

Fig. 22. Pentadentate dihydrosalen complex of manganese as peroxidase model.

As briefly summarized in Section 1.2.2.1, extensive evidence has been reported indicating that horseradish peroxidase Compound I is an oxo-ferryl [Fe =0] porphyrin n-cation radical and that Compound II is an oxo-ferryl porphyrin. Groves and co-workers have reported an inorganic model complex for Compound I [53, 54] and Balch and co-workers have described a Compound II model [55, 56]. These models each appear to have the expected compositions for the respective enzyme states that they are designed to mimic. 

The first application of EXAFS spectroscopy to the ferryl states of heme systems was reported by Penner-Hahn et al. in 1983 [143]. This work included a comparative study of the Groves and Balch model complexes, and of horseradish peroxidase Compounds I and II. The EXAFS spectra and corresponding Fourier transforms of the four high-valent systems (two proteins and two models), taken from a subsequent, more complete, analysis of the data [107], are displayed in Figs. 19 and 20. Table 2 contains a summary which shows the Fe-O(oxo) and Fe-Np bond lengths for a variety of oxidized heme proteins and their models. 

Table 2. Structural details for high-valent oxoiron (IV) states of horseradish peroxidase, myoglobin, cytochrome c peroxidase and relevant porphyrin model complexes ...

For the high-valent Compound I intermediate of the peroxidases and the appropriate model complex, EXAFS spectroscopy has unequivocally demonstrated the presence of a short 1.65 A Fe=0 bond. The published data are... 

C atalytic site of peroxidase is a heme, which is rapidly oxidized in its free form to hematin. p-Ethylphenol was polymerized using hematin as catalyst in an aqueous DMF (325). Iron-)VA -ethylenebis(salicyhdeneamine) (Fe-salen) also can be regarded as model complex of peroxidase. Fe-salen catalyzed an oxidative polymerization of various phenols such as 2,6-dimethylphenol, bisphenol A, cardanol, and urushiol analogues (251,293,326-329). The polymerization of 2,6-difluorophenol by Fe-salen produced a crystalline fluorinated PPO derivative (330). 

Peroxidase Model Catalyst. An iV,iV -bis(salicylidene)ethylenediamino iron [Fe(salen)] complex was found to be a cheap peroxidase model catalyst for oxidative polymerization of phenols with hydrogen peroxide (75-79). Hematin also polymerized ethylphenol in a reaction mechanism similar to that for HRP (80). 

Most of the model complexes for compound I are the derivatives of Fe(TPP) due to their stability. The HOMO s (highest occupied molecular orbital) of the porphyrin rings of these iron porphyrins are known to be A2u [73-75]. While Aiu and A2u characters of catalases and peroxidases are still controversial [53, 54, 76-82], as shown in Fig. 5, orbital pattern for the A2u and Aiu orbitals is very different [59, 83], thus, the reactivities of these two species are expected to be different. Especially that the pyrrole nitrogens of compound I having Aiu as HOMO is node indicates less interaction between the spin on the porphyrin ring and central oxo-ferryl orbitals. These considerations lead to the prediction that compound I whose HOMO is A2u is much reactive than Aiu lyP species. 

We have discussed model complexes and reactions of monooxygenase, mainly P-450, and peroxidases. The first generation of the studies was focused on the mimicking of many types of reactions catalyzed by P-450 such as hydroxylation and epoxidation. The second... 

Gosh, A., J. Almlof, and L. Que Jr. 1994. Density Functional Theoretical Study of Oxo(porphyroinato)iron(IV) Complexes, Models of Peroxidase Compounds I and II. J. Phys. Chem. 98, 5576. 

Cytochrome c and cytochrome c peroxidase (ccp) are physiological partners in the ccp reaction cycle structural, thermodynamic, and kinetic data are available for the protein-protein interaction [69-72]. A model indicates that the cyt c/ccp complex is stabilized by specific salt bridges with the hemes in parallel planes the Fe-Fe distance is 24 A, and the edge-edge distance is 16 A [70]. 

As part of a subsequent study concerning primarily second-site revertant yeast iso-l-cytochrome c variants, Hazzard et al. evaluated the effect of converting Lys-72 to an aspartyl residue by site-directed mutagenesis on the electron transfer kinetics of the cytochrome c-cytochrome c peroxidase complex [136]. Lys-72 was of interest for this purpose, because it is involved in the hypothetical model for the complex formed by these two proteins that was proposed by Poulos and Kraut on the basis of molecular graphics docking [106]. In these... 

First the structures of cytochrome cytochrome c peroxidase [21] are both known at high resolution. Although the precise three dimensional structure of the protein-protein complex is unknown (and, we shall argue, unknowable), molecular modeling has produced detailed stereochemical models for the c ccp complex which are subject to experimental testing and subsequent improvement, as detailed below. 

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