Catalase model studies

III) form of Lactobacillus plantarum is depicted in Fig. 13 [105,106]. The Mn centers are bridged by oxo, hydroxo, and car-boxylato ligands in a manner similar to the binuclear structures (8-10) in Sect. 16.1.4. A proposed mechanism for hydrogen peroxide dismutation by Mn catalase is presented in Fig. 14. A number of model studies of H2O2 disproportionation employing bridged binuclear Mn complexes have been conducted [107]. 

Hydrogen peroxide Model studies on catalases, peroxidases, and superoxide dismutases have provided insights into biological protection against oxidative damage. 

Several conclusions can be drawn from the model studies. First, it is clear that Mn is just as versatile as Fe or Cu and that Mn complexes can, with appropriate design, be synthesized in a variety of oxidation states and coordination enviromnents. A coimnon feature of the model chemistry is the observation of (/u.-0)(/u.-carboxylate)2Mn2 and (fx-0)2(ii-carboxylate)Mn2 core structures similar to those suggested for Mn catalase. By judicious protonation of the oxo bridge(s), it is possible to vary the Mn reduction potential of these structures over a wide range. 

On the basis of the arguments presented in Chapter 3 and a series of model studies (discussed in Chapters 4 and 6), the valence-electron bonding for the active forms of catalase, peroxidase, and cytochrome P-450 are formulated with uncharged oxygen atoms (instead of the high-valent metal-oxo formulations that are in contemporary favor). 

In addition, complexes with low- and high-molecular weight amines (ethylene-diamine, triethylenetetramine, butylamine, poly(ethyleneimine)) were tested as catalase models [75]. The examined polymer-metal catalysts were nearly as effective as the catalase models. Pshezhetskii et al. [76] studied the mechanism of hydrogen peroxide decomposition by PAA-Fe complex in the presence of diethylenetriamine as a cofactor (see the lower scheme on p. 12). 

Although, salen Mn complexes for therapeutic use were originally conceived as SOD mimetics, it soon became clear that EUK-8 also exhibited catalase activity, the ability to metabolize hydrogen peroxide (75). The catalase activity of EUK-8 was not unexpected, since Mn porphyrins had been studied as catalase models by the Meunier laboratory (16) and, like the porphyrins, salen ligands form stable complexes with Mn(III) (6). As described previously (77), similar to that of mammalian heme-iron based catalases (78), the catalase activity of salen Mn complexes is not saturable with respect to hydrogen peroxide. As has been reported for protein catalases (18), salen Mn complexes exhibit peroxidase activity, in the presence of an electron donor substrate, as an alternative to a catalatic pathway. This supports the analogy between the behavior of these mimetics and that of catalase enzymes, and is consistent with the following mechanistic scheme (76,17) ... 

The kinetics of reactions of NO with ferri- and ferro-heme proteins and models under ambient conditions have been studied by time-resolved spectroscopic techniques. Representative results are summarized in Table I (22-28). Equilibrium constants determined for the formation of nitrosyl complexes of met-myoglobin (metMb), ferri-cytochrome-c (Cyt111) and catalase (Cat) are in reasonable agreement when measured both by flash photolysis techniques (K= konlkQff) and by spectroscopic titration in aqueous media (22). Table I summarizes the several orders of magnitude range of kon and kQs values obtained for ferri- and ferro-heme proteins. Many k0f[ values were too small to determine by flash photolysis methods and were determined by other means. The small values of kQ result in very large equilibrium constants K for the... 

In part motivated by the desire to model biological redox processes, there have been many studies in which Robson-type macrocycles (205) (R = H) have been employed to form dinuclear manganese species.For example, a novel macrocyclic heterodinuclear catalase-like model complex of type (206) has been reported. " This complex can dismute hydrogen peroxide to dioxygen in basic aqueous solution. 

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