Redox metallic ions

The beauty of bromide-mediated oxidations is that they combine mechanistic complexity with practical simplicity and, hence, utility. They involve an intricate array of electron transfer steps in which bromine atoms function as go-betweens in transfering the oxidizing power of peroxidic intermediates, via redox metal ions, to the substrate. Because the finer mechanistic details of these elegant processes have often not been fully appreciated we feel that their full synthetic potential has not yet been realized. Hence, we envision further practical applications in the future. 

REDOX METAL IONS, OXIDATIVE STRESS AND NEURODEGENERATIVE DISEASES... 

Another approach to isolating redox metal ions in stable inorganic matrices, thereby creating oxidation catalysts with unique activity/selectivity relationships, is to incorporate them in a zeolite lattice framework. This is fundamentally different to the metal ion exchanged (i.e. impregnated) zeolites described earlier and the ship in the bottle type zeolites61,62 where a metal... 

From a mechanistic viewpoint it is worth noting that the TS-1 catalyst contains the same chemical elements in roughly the same proportions as the Shell amorphous TiIV/Si02 catalyst referred to earlier. However, the former displays a much broader range of activities than the latter. A possible explanation may be that the TS-1 catalyst contains more (or more active) isolated titanyl centres than the amorphous Ti1v/Si02. Based on the quite remarkable results obtained with TS-1 we expect many more examples of redox zeolites, i.e. zeolites, alpos, etc. modified by isomorphous substitution with redox metal ions in the crystal lattice, as selective oxidation catalysts.66... 

Biocatalysts do not operate by different scientific principles from organic catalysts. The existence of a multitude of enzyme models including oligopeptidic or polypeptidic catalysts proves that all enzyme action can be explained by rational chemical and physical principles. However, enzymes can create unusual and superior reaction conditions such as extremely low pfCa values or a high positive potential for a redox metal ion. Enzymes increasingly have been found to catalyze almost any reaction of organic chemistry. 

The neurotoxic properties of Af) have also been shown to be associated with methionine at residue 35 of A (Met35) (Butterfield and Boyd-Kimball, 2005). The substitution of methionine by norleucine from Af) abolishes free radical production, protein oxidation, and toxicity to hippocampal neurons (Butterfield and Boyd-Kimball, 2005). In addition, substitution of a carbon atom for the S atom of methionine completely abrogates A (l-42) neurotoxicity (Yatin et al., 1999 Butterfield and Kanski, 2002), and in vivo studies indicate methionine residue 35 is central for A -induced oxidative damage (Yatin et al., 1999). Studies from our laboratory (Varadarajan et al., 2000) and others (Curtain et al., 2001) showed that Cu bound to Af)(l-42) interacts with Met35 residue to produce free radicals in the absence of methionine in A ( 1 -42) redox metal ions play no role in the oxidative stress and neurotoxicity induced by the peptide (Varadarajan et al., 2000, 2001). Taken together these results are consonant with the notion that Af)-induced protein oxidation may in part account for neurodegeneration in AD brain (Butterfield and Boyd-Kimball,... 

Redox metal ions, particularly iron and copper, react with hydroperoxides, initiating further autoxidation and producing undesirable decomposition products. Complete removal of these metal ions is not possible, but steps can be taken to reduce their effect. Chelating agents such as EDTA, citric acid, phosphate, and polyphosphates may reduce the effective metal ion concentration. Their efficacy depends on pH, and they may also show prooxidant activity. The role of metal ions in hydroperoxide decomposition in food emulsions has been reviewed recently (52). 

Framework substitution of Al, Si or P by a redox metal ion leads, in general to more stable redox molecular sieves (Figure 4). So-called isomorphous substitution, in udiich the metal ion is coordinated tetrahedrally by four oxygen atoms should be possible when the cuion/ oxygn between 0.22S and 0.414 [25]. It should be noted, however, tiiat the oxidation state of the metal and, hence, structure and charge of tire frameworic, may change substantially when an as-synthesized material is calcined. For example, Cr-substituted sieves generally contain Ci in the as-synthesized material but on calcination this is transformed to Cr. Since the latter contains two extra-framework Cr == O bonds it can only be anchored to a surface defect site rather than isomorphously substituted. By the same token, as-synthesized... 

In the synthesis of silica-based materials a mineralizer (OH , F") is required to regulate the dissolution and condensation process, i.e. synthesis is generally carried out at high pH. In contrast, (redox) aluminophosphates are crystallized from gels prepared by mixing an alumina slurry with a solution of the redox metal ion in aq. H3PO4 and the template, i.e. synthesis occurs at low pH. 

The discovery, in the mid-eighties, of the remarkable activity of TS-1 as a catalyst for selective oxidations with aqueous H2O2 fostered the expectation that this is merely the progenitor of a whole family of redox molecular sieve catalysts with unique activities. However, the initial euphoria has slowly been tempered by the realization that framework substitution/attachment of redox metal ions in molecular sieves does not, in many cases, lead to a stable heterogeneous catalyst. Nevertheless, we expect that the considerable research effort in this area, and the related zeolite-encapsulated complexes, will lead to the development of synthetically usefril systems. In this context the development of chiral ship-in-a-bottle type catalysts for intrazeolitic asymmetric oxidation is an important goal. Such an achievement would certainly justify the appellation mineral enzyme . 

Based on the quite remarkable results obtained with TS-1 we expect that many more examples of microporous solids modified by isomorphous substitution with redox metal ions in the crystal lattice will be described in the future (see Fig. 12). Indeed, the scope for developing unique oxidation catalysts based on the concept of site-isolation in zeolites, silicalites, alpos and sapos is enormous [37], In addition to varying the redox metal the size and hydrophobicity of the cavity can be tuned by, for example, varying Si/Al ratios to provide a variety of unique heterogeneous catalysts for liquid phase oxidation. 

There is considerable current interest in the design of new catalysts by interchelating clay minerals of the smectite type with redox metal ions, leading to the formation of oxidation catalysts with interesting (shape-selective) properties [38]. For example, vanadium-pillared montmorillonite (V-PILC) proved to be an... 

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 latter is analogous to the hydrothermal synthesis of zeolites and related molecular sieves (see later). Redox metal ions can be incorporated into acidic clays or zeolites by ion exchange, and oxoanions can be similarly exchanged into hydrotalcite-like anionic clays [30]. 

Alternatively, redox metal ions can be incorporated into framework positions of zeolites and related molecular sieves by hydrothermal synthesis or post-synthesis modifications [15]. A suitable choice of molecular sieve, with an appropriate pore... 

The above series of catalysts studied showed a comparable activity of phenol hydroxylation over some of the zeolites-based catalysts. Until now, the nature of cobivalent metal ions studied was of redox in nature with a capability of switching multiple oxidation slates. Interest emerged to see the influence of a non-redox metal ion where electronic influence on copper is minimal and magnesium was chosen as an ideal candidate. In continuation, a scries of CuMgAI ternary hydrotalcites were synthesized with the goal to elucidate the influence of divalent non-transition metal cation on the catalytic performance. 

P. A. Voziyan, R. G. Khalifah, C. Thibaudeau, A. Yildiz, J. Jacob, A. S. Serianni, and B. G. Hudson, Modification of proteins in vitro by physiologieal levels of glucose Pyridoxamine inhibits conversion of Amadori intermediate to advanced glycation end-products through binding of redox metal ions, J. Biol. Chem., 278 (2003) 46616-46624. 

The quest for selective catalysts for the dream reactions discussed at the beginning of this article continues unabated. There is still a great need for systems that create gas-phase conditions in the liquid phase. One approach is maybe to isolate redox metal ions, by isomorphous substitution, in the lattice of molecular sieves [67]. Such redox molecular sieves may be viewed as inorganic en mes containing an active site in which there is no room for solvent molecules in addition to the substrate, i.e. gas phase conditions in the liquid phase. 

When certain redox metal ions and reducing agents are present, H2O2 toxicity is markedly potentiated. In model systems, cupric was by far the most effective metal ion, enhancing toxicity over a wide range of medium conditions to levels approaching those measured for HOCl. In contrast, ferric complexes commonly used as catalysts in H2O2 oxidation reactions were much less effective, and measurable effects could be demonstrated only under a narrowly defined set of conditions. Mechanisms of toxicity... 

Voziyan, P.A., Khalifah, R.G., Thibaudeau, C., Yildiz, A., Jacob, J., Serianni, A.S., and Hudson, B.G., 2003. Modification of proteins in vitro by physiological levels of glucose pyridoxamine inhibits conversion of amadori intermediates to advanced glycation end-products through binding of redox metal ions. Journal of Biological Chemistry. 27S 46616-46624. 

Such a redox-switch mechanism results from the blocking of the associative process at the Cu state, imposed by the caUxarene funnel. All of this suggests that the embedment of a reactive redox metal ion in a funnel-like cavity can play a crucial role in catalysis, particularly for metallo-enzymes associating electrOTi transfer and ligand exchange. 

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