Catalase model complexes

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. 

Early proposals suggested [72] that catalase contains a p-oxo-bis(p-carboxylato)-dimanganese core. The UV-Vis spectra of this structural motif present in model complexes exhibit 480-520 nm d-d absorptions [73] similar to the UV-Vis absorption bands of manganese catalases. The EPR studies of oxidized T. ther-mophilus catalase [74] also suggested a MnIIIMnI" p-oxo-bis(p-carboxy 1 ato) core as a possible structural motif for the active site. 

Many manganese complexes decompose dihydrogen peroxide, but we limit our discussion to the functional dinuclear ones the catalase activity of bis-dinuclear (tetranuclear) photosystem II (PSII) models is discussed later. Furthermore, mainly model complexes reported in the last 5 years are discussed in detail since previous work is covered in several excellent reviews [1,2b,3a,5,8-12],... 

Three Mn catalases have been purified and characterized, and all appear to have similar Mn structures (17). The Mn stoichiometry is ca. 2 Mn/subunit, suggesting a dinuclear Mn site. The optical spectrum of the as-isolated enzyme has a broad weak absorption band at ca. 450-550 nm in addition to the protein absorption at higher energies. This spectrum is similar to those observed for Mn(III) superoxide dismutase and for a variety of Mn(III) model complexes, thus implying that at least some of the Mn in Mn catalase is present as Mn(III). In particular, the absorption maximum at ca. 500 nm is similar in energy and intensity to the transitions seen for oxo-carboxylato-bridged Mn dimers, suggesting that a similar core structure may be seen for Mn catalase (18). 

The electronic spectrum of the dimanganese(III) form of catalase from Thermus thermophilus shows an intense absorption at 450 nm with a shoulder at 500 nm. EPR studies show that Mn Mn , Mn Mn , and Mn Mn forms are also accessible and the Mn Mn protein exhibits a 16-line spectrum, characteristic of a p-oxo bridged system 202). Comparison with the model complexes leads to prediction of p-oxo-bis(/[i-carboxylato)dimanganese(III) structure for the catalase. X-ray crystal data (203) have indicated an Mn—Mn distance of 3.6 3 A for the enzyme this appears to be inconsistent with the above proposal but, as the X-ray data are at rather low (3 A) resolution, this may be the least reliable piece of data. 

Numerous model complexes that model one or more traits of the catalase enzyme have been prepared over the years (discussed later). Several systems that mimic the function of this enzyme have been reported, and a selection of these will be discussed in Section V, Reactivity. Other models with respect to structures or physical properties of the catalase enzyme will be presented in the ensuing sections of this review. 

UV-vis spectroscopy proved particularly enlightening with respect to the catalase system (23, 30, 132). The spectra of model complexes bridged by carboxylate and oxo bridges were quite similar to those observed for the catalase. This led researchers to the proposal that such a motif might also be present, a hypothesis that has been borne out by the crystal structure of the catalase (125). 

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). 

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. 

To gain insight into the mechanisms of these enzymes, a variety of Mn complexes that mimic the active site have been developed [28]. Dismukes and coworkers reported the first functional catalase model that exhibits high activity towards H2O2 decomposition even after turnover numbers of 1000, no loss of activity towards H2O2 decomposition was observed [29]. The dinuclear Mn -complex is based on ligand 1... 

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) ... 

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