Superoxide disproportionation

In the literature there are no quantitative studies on the kinetics and thermodynamics of stoichiometric superoxide reactions with metal centers in general, and metalloporphyrins in particular. More precisely, superoxide concentration and temperature dependent kinetic and thermodynamic measurements were never reported and consequently the rate constants, activation parameters or binding constants for this t5rpe of reactions (Scheme 15) are not known. (The catalytic rate constants for the superoxide disproportionation, i.e., dismutation, by metal complexes are known (see earlier), however in those measurements the concentration of a catalytic amount... 

Fig. 1.15 Second-order superoxide disproportionation constant vs pH at 25 °C. Potassium superoxide ( 1 mM) in pH a 12 was mixed in a stopped-flow apparatus with buffers at various pH s and the change in absorbance at 250 nm monitored. The decays were second-order and data were treated in a similar manner to that described in Fig. 1.3. The full line fits Eqn. (1.231) using the parameters given in the text. Reprinted with permission from Z. Bradid and R. G. Wilkins, J. Am. Chem. Soc. 106, 2236 (1984). (1984) American Chemical Society.

PKa = 4.4, in water), less than O2 that the potential of 0 2 /H02 becomes higher than that of 02/0 2 . As a consequence, the superoxide disproportionates into O2 and HO2 , in the presence of proton sources. An evaluation of the solvent effect on the redox potential of the 02/0 2 system is not easy because of the difficulty in comparing the potential scales in various media but, obviously, assuming that the junction potential between the aqueous SCE and every solvent does not exist is far from correct [12] adopting any extrathermodynamic hypothesis would be better. The important shift in the one-electron reduction of O2 to 0 2 , almost 0.5 V, has been attributed to the solvation of 0 2 , which is much more strongly solvated by water than by the aprotic media hexamethylphosphorotriamide (HMPT) is the solvent where the 2/0 2 potential is... 

The major in situ process that results in the formation of H202 is undoubtedly photochemical (e.g., 12, 15, 49, 50). Photochemical formation of H202 in fresh and salt waters probably results from the disproportionation of the superoxide ion radical, 02 (8, 9, 15, 51, 52). The kinetics of superoxide disproportionation are well established (53), and its steady-state concentration can be calculated. Because of the known effects of superoxide ion in cells (47), its presence in surface waters may be important in biologically mediated processes. However, other sources, such as biological formation (e.g., 45, 54), redox chemistry (21, 24, 29, 31, 32), wet (e.g., 55) and dry (50, 56, 57) deposition, and surfaces (e.g., 58) may also be important. 

During catalysis of superoxide disproportionation, the copper centre is reversibly oxidized and reduced by successive encounters with superoxide, giving 02 and H202 (equations 67 and 68). The zinc(II) almost certainly has a structural role in the formation and stabilization of the active site,1352 and indirectly in enhancing the reactivity of the copper. 

Little is known about the mechanism of superoxide disproportionation in these cases, except that it appears to be different from that of the Cu/Zn enzyme. There also appear to be some differences between the Mn and Fe enzymes. 

A number of investigators have attempted to construct kinetic models of the light-mediated transformations of iron in natural waters. For example, Miller et al. [98] used a relatively simple scheme incorporating LMCT, reduction of inorganic Fe(III) by superoxide, ferrous iron oxidation and superoxide disproportionation to model the generation and decay of ferrous iron and... 

Disproportionation of NO to N20 and N02 is thermodynamically favorable (AG° = —544 kJ per mole of N20), but it does not occur measurably without catalysis. There are indications that transition metal complexes can catalyze the disproportionation,26 but the reported rates are quite slow relative to the rates for catalyzed superoxide disproportionation discussed below. 

An alternative metal ion-catalyzed mechanism for superoxide disproportionation involves the Lewis acidity of the metal center rather than its redox properties. In this mechanism, the metal center activates coordinated superoxide toward reaction with another superoxide ... 

There is no question that superoxide is formed during the normal course of aerobic metabolism, although it is difficult to obtain estimates of the amount under varying conditions, because, even in the absence of a catalyst, superoxide disproportionates quite rapidly to dioxygen and hydrogen peroxide (Reaction... 

Several transition-metal complexes have been observed to catalyze superoxide disproportionation in fact, aqueous copper ion, Cu +, is an excellent SOD catalyst, comparable in activity to CuZnSOD itself Free aqueous Cu + would not itself be suitable for use as an SOD in vivo, however, because it is too toxic (see Section III) and because it binds too strongly to a large variety of cellular components and thus would not be present as the free ion. (Most forms of complexed cupric ion show much less superoxide dismutase activity than the free ion.) Aside from aqueous copper ion, few other complexes are as effective as the SOD enzymes. 

Two mechanisms (Reactions 5.96 to 5.99) have been proposed for catalysis of superoxide disproportionation by metal complexes and metalloenzymes. ... 

If a metal complex can be reduced by superoxide and if its reduced form can be oxidized by superoxide, both at rates competitive with superoxide disproportionation, the complex can probably act as an SOD by Mechanism I. Mechanism II has been proposed to account for the apparent catalysis of superoxide disproportionation by Lewis acidic nonredox-active metal ions under certain conditions. However, this mechanism should probably be considered possible for redox metal ions and the SOD enzymes as well. It is difficult to distinguish the two mechanisms for redox-active metal ions and the SOD enzymes unless the reduced form of the catalyst is observed directly as an intermediate in the reaction. So far it has not been possible to observe this intermediate in the SOD enzymes or the metal complexes. 

The x-ray structural results described above apply only to the oxidized form of the protein, i.e., the form containing Cu . The reduced form of the enzyme containing Cu is also stable and fully active as an SOD. If, as is likely, the mechanism of CuZnSOD-catalyzed superoxide disproportionation is Mechanism I (Reactions 5.96-5.97), the structure of the reduced form is of critical importance in understanding the enzymatic mechanism. Unfortunately, that structure is not yet available. 

The mechanism of superoxide disproportionation catalyzed by CuZnSOD is generally believed to go by Mechanism I (Reactions 5.96-5.97), i.e., reduction of Cu to Cu by superoxide with the release of dioxygen, followed by reoxidation of Cu to Cu by a second superoxide with the release of HOa or H2O2. The protonation of peroxide dianion, 02, prior to its release from the enzyme is required, because peroxide dianion is highly basic and thus too unstable to be released in its unprotonated form. The source of the proton that protonates peroxide in the enzymatic mechanism is the subject of some interest. 

It has been suggested that a major portion of brain copper is in the form of Cu Zn SOD [330] and that seizures may be due to a lack of superoxide disproportionation in the brain [331]. Since copper complexes in general have... 

If Cu-Zn SOD has radioprotectant activity because of its ability to disproportionate superoxide [504], then small molecular weight copper complexes, which are also known to disproportionate superoxide [287-295], might also have radioprotectant activity. Recent studies document radioprotectant activity for Cu(II)(3,5-DIPS)2 which has superoxide disproportionating reactivity. 

Interestingly, the kinetic results of an earlier study about the catalytic properties of Cu-histidine complexes toward superoxide disproportionation have been interpreted by two alternative mechanisms similar to those described above (357). The [CuHis2H] complex was found to be the catalytically active species, with a = 3.4 x 10 M sec independent of pH in the range 2-7. 

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