Superoxide, manganese complexes

Baudry, M., Etienne, S., Bruce, A., Palucki, M., Jacobsen, E. and Malfroy, B. (1993). Salen-manganese complexes are superoxide dismutase-mimics. Biochem. Biophys. Res. Commun. 192, 964-968. 

Baudry M et al (1993) Salen-manganese complexes are superoxide dismutase-mimics. Biochem Biophys Res Com 192 964-968... 

Dinuclear Manganese Complexes as Models for the Manganese Catalase. As discussed previously, the manganese catalase has a dinuclear active site that is thought to function by cycling redox states between Mn(II)2 and Mn(III)2. Although the [Mn(IV)(salpn)(/z2-0)]2 chemistry nicely explains the alternate catalase reactions of the OEC, this system is an inappropriate model for the Mn catalase because the redox cycle in that enzyme is lower and the core structure is believed to be dramatically different. In fact, a [Mn(III/IV)(/z2-0)]2 superoxidized state of the Mn catalase has been identified and shown to be inactive. 

The manganese complexes that have been prepared to date cover a range of structural types and ligands. Due to the self-dismutation of superoxide (2.0-3.2 X 10s M [ s ) (52, 63), these complexes need to be quite efficient to quality as catalysts of superoxide dismutation. Several complexes have proven to be competent MnSOD mimics. Un-... 

The complex of manganese with desferrioxamine B (429-432), reported to be a MnSOD mimic in 1987, illustrates this point. In the initial studies, the cytochrome c assay was applied, and this compound was reported to be a catalytic MnSOD mimic. Follow-up studies by Riley and co-workers by stopped-flow techniques showed that this complex interacts at best on a stoichiometric level with superoxide, but it could not be considered to be a catalyst and was termed inactive (428). This occurred due to interactions with cytochrome c wherein the manganese complex interfered with the reduction of cytochrome c, leading in effect to a false positive. Thus, although some... 

Most manganese complexes that have been reported to react with superoxide, however, do not react catalytically. Several have been reported by various groups in attempts to generate catalytic systems, but these only show stoichiometric interactions with superoxide. Examples of this group of complexes includes the recently reported seven-coordinate Mn11 complex, with the same ligand and a structure similar to the complex shown in Fig. 25 (229). 

Studies of Superoxide with Manganese Complexes and Manganese Superoxide Dismutase from Escherichia coli... 

The mechanisms by which manganese complexes and manganese superoxide dismutase react with superoxide radicals are of interest as knowledge of the kinetic parameters and the reaction pathways may allow the synthesis of model compounds with specific chemical features. These compounds may then have clinical application or may allow the control of specific redox chemistry in catalytic processes. 

Besides the superoxide dismutation mechanism, the reactivity of metal centers, in particular manganese complexes, toward NO is very much dependent on the possibility for binding a substrate molecule. As it will be shown later, the possibility that MnSOD enzymes and some mimetics can react with NO has been wrongly excluded in the literature, simply based on the known redox potential for the (substrate) free enzymes, mimetics, and NO, respectively. Therefore, the general fact that, upon coordination, redox potentials of both the metal center and a coordinated species are changed should be considered in the case of any inner-sphere electron-transfer process as a possible reaction mechanism. 

Another area of active research is the development of stable low molecular weight metal complexes, which could serve as SOD mimics. Fridovich has described a complex of mangsmese (III) with desferral, which can catalyse the dismutation of superoxide anion in vitro and can protect green algae against paraquat toxicity (Beyer and Fridovich, 1989). This manganese-desferral complex was evaluated in models of circulatory shock and also found to improve survival rate (de Garavilla etal., 1992). 

Thus, the mechanism of MT antioxidant activity might be connected with the possible antioxidant effect of zinc. Zinc is a nontransition metal and therefore, its participation in redox processes is not really expected. The simplest mechanism of zinc antioxidant activity is the competition with transition metal ions capable of initiating free radical-mediated processes. For example, it has recently been shown [342] that zinc inhibited copper- and iron-initiated liposomal peroxidation but had no effect on peroxidative processes initiated by free radicals and peroxynitrite. These findings contradict the earlier results obtained by Coassin et al. [343] who found no inhibitory effects of zinc on microsomal lipid peroxidation in contrast to the inhibitory effects of manganese and cobalt. Yeomans et al. [344] showed that the zinc-histidine complex is able to inhibit copper-induced LDL oxidation, but the antioxidant effect of this complex obviously depended on histidine and not zinc because zinc sulfate was ineffective. We proposed another mode of possible antioxidant effect of zinc [345], It has been found that Zn and Mg aspartates inhibited oxygen radical production by xanthine oxidase, NADPH oxidase, and human blood leukocytes. The antioxidant effect of these salts supposedly was a consequence of the acceleration of spontaneous superoxide dismutation due to increasing medium acidity. 

The inhibition of lipid peroxidation by metalloporphyrins apparently depends on metal ions because only compounds with transition metals were efficient inhibitors. Therefore, the most probable mechanism of inhibitory effects of metalloporphyrins should be their disuniting activity. Manganese metalloporphyrins seem to be more effective inhibitors than Trolox (/5o = 204 pmol I 1) and rutin (/50 112 pmol I 1), and practically equal to SOD (/50= 15 pmol I 1). The mechanism of inhibitory activity of manganese and zinc metalloporphyrins might be compared with that of copper- and iron-flavonoid complexes [167,168], which exhibited enhanced antiradical properties due to additional superoxide-dismuting activity. 

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