Superoxide dismutation , mimetics

II. Catalytic Superoxide Dismutation by Seven-Coordinate Manganese and Iron Complexes as SOD Mimetics... 

That inner-sphere electron transfer plays an important role within the SOD mechanism is shown by our preliminary experiments with the eight-coordinate Mn(II) complex (Fig. 11). Although the redox potential of this complex is similar to the redox potentials of some proven seven-coordinate Mn(II) SOD mimetics (approximately +0.78V vs. NHS) (13a,g,31), the studied eight-coordinate Mn(II) complex demonstrates no ability for catalytic superoxide dismutation. This can be explained in terms of the saturated coordination geometry around the metal center and shows that, for SOD activity, the complex redox potential is not the only important requirement. In the case of these complexes, with a relatively high redox potential, coordination of superoxide is crucial for its efficient reduction. 

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. 

Mn(III)TMPyP is a manganese porphyrin that acts as a superoxide dismutase (SOD) mimetic and peroxynitrite decomposition catalyst (Han et al., 2001). SOD mimetics described to date are unstable and are capable of catalyzing undesired side reactions in addition to the dismutation of the superoxide radical. Mn(III)TMPyP is an SOD mimetic with increased stability to pH and hydrogen peroxide. The rate constants for superoxide dismutation and peroxynitrite decomposition are 3.9 X 10 M s and... 

Thus, superoxide can react with almost all redox-active metal centers (Scheme 1). In general, going through similar redox reaction steps metal complexes can interact with superoxide either as catalysts for its dismutation (superoxide dismutase (SOD) mimetics), or in a stoichiometric manner (Scheme 1). 

Stopped-flow measurements with superoxide in aqueous solution at physiological pH are not possible due to its fast self-dismutation under these conditions. Therefore, the indirect assays such as McCord-Fridovich, adrenalin and nitroblue tetrazolium (NET) assays are widely used in the literature, not only for qualitative but also for quantitative detection of SOD activity of small molecular weight mimetics 52). Not going into details, we just want to stress that the indirect assays have very poor even qualitative reliability, since they can demonstrate the SOD activity of the complexes which does not react with superoxide at all. It has been reported in the literature that this is caused by the interference of hydrogen peroxide 29). We have observed that the direct reaction between complexes and indicator... 

Keywords Superoxide Nitric oxide Manganese superoxide dismutase Manganese SOD mimetics (mimics) Peroxynitrite Nitric oxide dismutation Nitric oxide reduction. 

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