Proteins, transition metal/protein catalysts

Scheme 2.19 Asymmetric reduction of alkene 46 using a hybrid transition metal/protein catalyst.

The efficient removal of O2 and H2O2 vvill diminish OH formation and therefore antioxidant defence systems have evolved to limit their accumulation. Enzymic and low molecular weight antioxidants exist to scavenge free radicals as self-protection mechanisms. Some proteins exhibit antioxidant properties because they chelate transition-metal catalysts. The significance of antioxidants in relation to inflammatory joint disease is discussed below. 

Some researchers have begun to explore the possibihty of combining transition metal catalysts with a protein to generate novel synthetic chemzymes . The transition metal can potentially provide access to novel reaction chemistry with the protein providing the asymmetric environment required for stereoselective transformations. In a recent example from Reetz s group, directed evolution techniques were used to improve the enantioselectivity of a biotinylated metal catalyst linked to streptavidin (Scheme 2.19). The Asn49Val mutant of streptavidin was shown to catalyze the enantioselective hydrogenation of a-acetamidoacrylic acid ester 46 with moderate enantiomeric excess [21]. 

Lipid hydroperoxides are fairly stable molecules under physiological conditions, but their decomposition is catalysed by transition metals and metal complexes (O Brien, 1969). Both iron(II) and iron(III) are effective catalysts for hydroperoxide degradation, but the former is more so (Halliwell and Gutteridge, 1984). These include complexes of iron salts with low molecular weight chelates, non-haem iron proteins, free haem, haemoglobin, myoglobin. 

Compounds such as superoxide anion and peroxides do not directly interact with lipids to initiate oxidation they interact with metals or oxygen to form reactive species. Superoxide anion is produced by the addition of an electron to the molecular oxygen. It participates in oxidative reactions because it can maintain transition metals in their active reduced state, can promote the release of metals that are bound to proteins, and can form the conjugated acid, perhydroxyl radical depending on pH, which is a catalyst of lipid oxidation (39). The enzyme superoxide dismu-tase that is found in tissues catalyzes the conversion of superoxide anion to hydrogen peroxide. 

These zeolite-encaged metal complexes are of importance as catalysts, too. From this point of application they possess two particular features each catalytic centre are separated, and the stability of the complex is enhanced (since the zeolite- cage protects the molecule from decomposition). Due to these features the zeolite encaged metal complexes resemble in a certain extent to enzymes, as well, where the catalytic centre might be a transition metal ion, and the stability and steric constraints are provided by the protein. In both systems the complexes of multivalent transition metal ions can catalyze the process of oxygen transfer for mild oxidations. 

A discussion of catalysis would not be complete without a comparison of the catalysts we normally encounter in the laboratory or in industry with those that occur naturally (i.e., enzymes). Enzymes are proteins that are either soluble in the aqueous medium of the cell or attached to a cellular membrane. Soluble enzymes resemble homogeneous transition metal catalysts in ways other than their solubility characteristics. Enzymes have at least one region that serves as... 

---