Reductive Pathways

FIGURE 5.1 Reduction of specific substrates for aldo/keto reductases. 

The main human AKRs have been cloned, expressed, and their substrate reactivity profiles and tissue and organ distribution determined. 

A few typical examples of CBR-catalyzed reduction of xenobiotics include the reduction of the antipsychotic haloperidol (6), the P450 inhibitor metyrapone (6), the oral hypoglycemic acetohexamide (6), and the anticoagulant warfarin (7). 

The catalytic activity of cytochrome P450 is not restricted to oxidation. Under certain conditions, especially anaerobic conditions or with certain substrates, it can function as a reductase. For example, P450 can catalyze the reductive removal of halide from polyhalo-genated alkanes such as hexachloroethane or halothane (8,9). 

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Still has also carried out mechanistic experiments9 3 from which he could deduce that the major reduction pathway is by attack of hydride ion at the sulphur atom. This conclusion was deduced from the fact that reduction with sodium borodeuteride-aluminium oxide gave a sulphoxide that had only incorporated about 25% mole equivalent of deuterium on to a methyl carbon atom bound to the sulphur atom. The mechanistic pathway for direct reduction is outlined in equation (38), whereas the pathway whereby deuterium could be incorporated is portrayed in equation (39). These reactions support the proposed mechanism for the hydride reduction of sulphones as outlined in Section III.A.l, namely that attack at sulphur by hydride ions may occur, but will be competitive with proton abstraction in cases when the attack at sulphur is not facilitated. 

Under different conditions (in aqueous electrolyte) the selectivity of the cleavage reaction may be perturbed by the occurrence51-53 of a dimerization process. Thus, while the major process remains the two-electron reductive pathway, 20% of a dimer (y diketone) may be isolated from the cathodic reduction of PhC0CH2S02CH3. The absence of crosscoupling products when pairs of / -ketosulphones with different reduction potentials are reduced in a mixture may indicate that the dimerization is mainly a simple radical-radical coupling53 and not a nucleophilic substitution. 

The scope and limitations for transfer hydrogenation employing either the iron porphyrin system or the combination of iron compound/terpy/PPhs are listed in Table 8. In most cases, the FeCVterpy/PPhs system displays a higher activity. Except for chloromethyl- and cyclopropyl-acetophenone, the desired products were obtained in good to excellent yields. It should be noted that a ring opened product was not observed when cyclopropyl acetophenone was employed. Hence, a radical-type reduction pathway was excluded and a hydride mechanism appeared to be reasonable. 

Both aerobic and reductive pathways were suggested for the degradation of 1,1,2-trichlo-roethane (Castro and Belser 1990)—a dominant aerobic pathway to chloroacetate and glyoxylate, and simultaneously a minor reductive reaction, which must also involve an elimination reaction with the formation of chloroethene (Figure 7.66). 

Castro CE, DM Riebeth, NO Belser (1992b) Biodehalogenation the metabolism of vinyl chloride by Methylosinus trichosporium OB-3b. A sequential oxidative and reductive pathway through chloroethylene oxide. Environ Toxicol Chem 11 749-755. 

Wu J-f, C-y Jiang, B-j Wang, Y-f Ma, Z-p Liu, S-j Liu (2006) Novel partial reductive pathway for 4-chloro-nitrobenzene and nitrobenzene degradation in Comamonas sp. strain CNB-1. Appl Environ Microbiol 12 1759-1765. 

FIGURE 10.8 Reductive pathways in degradation of pyridine. (From Neilson, A.H. and Allard, A.-S., The Handbook of Environmental Chemistry, Vol. 3J, pp. 1-80, Springer, Heidelberg, 1998. With permission.)... 

An increase in the fraction of the four-electron reduction pathway at more reducing potentials (Fig. 18.10a, b) may be rationalized within at least two mechanisms. The first is based on the kinetic competition between the release of H2O2 from the ferric-hydroperoxo intermediate [Reaction (18.16) in Fig. 18.11] and its (reversible) reduction to a ferrous-hydroperoxo species, which undergoes rapid 0-0 bond heterolysis (18.13b). Because H2O2 and particularly HO2 are more basic ligands... 

Interpreting these results on a detailed molecular basis is difficult because we have at present no direct structural data proving the nature of the split Co(IIl/lI) voltammetry (which seems critical to the electrocatalytic efficacy). Experiments on the dissolved monomeric porphyrin, in CH-C solvent, reveal a strong tendency for association, especially for the tetra(o-aminophenyl)porphyrin. From this observation, we have speculated (3) that the split Co(III/II) wave may represent reactivity of non-associated (dimer ) and associated forms of the cobalt tetra(o-aminophenyl)porphyrins, and that these states play different roles in the dioxygen reduction chemistry. That dimeric cobalt porphyrins in particular can yield more efficient four electron dioxygen reduction pathways is well known (24). Our results suggest that efforts to incorporate more structurally well defined dimeric porphyrins into polymer films may be a worthwhile line of future research. 

Figure 13.13.2 Alternative reduction pathway of trimethylamine oxide to dimethy-lamine and formaldehyde.

In summary, two general pathways are now accepted as the reaction basis of pyridine degradation by bacteria. One involves (i) hydroxylation reactions, followed by reduction, e.g., on Bacillus strain 4 and the other (ii) (aerobic) reductive pathway(s) not initiated by hydroxylations, e.g., on Nocardia strain Zl [348], Two review articles, one by Kaiser [320] and the other by Fetzner [326] gave the complete microbial metabolic pathways for several nitrogen compounds carried out in the presence of a variety of microorganisms, some of them previously studied by Professor Lingens [349], The complete degradation pathways of pyridine are shown in Fig. 29. 

In contrast to Co-porphyrin complexes, the direct four-electron reduction of 02 has been only very rarely claimed to be catalyzed by a cobalt phthalocyanine 404 407 In particular cofadal binuclear Co-Pc complexes immobilized on pyrolytic graphite catalyze only the two-electron electroreduction of 02 to H202.408,409 However, recent work has established that an electropolymerized Co-Pc derivative provides a stable four-electron reduction pathway over a wide pH range 410... 

Clearly a plot of JV/D//R vs. o> X 2 will allow us to make some deductions. If, for example, kx = 0 i.e. there is no direct four-electron reduction pathway for 02 at the electrode, and we obtain from equation 6 ... 

The difference in the self-exchange rates of the two cobalt couples favors the oxidative pathway by a factor of 300. (For a further discussion of the above and other self-exchange rates, see B. S. Brunschwig, C. Creutz, D. H. Macartney, T.-K. Sham, and N. Sutin, Faraday Discuss. Chem. Soc., No 74, in press). Evidently the difference in the intrinsic barriers is large enough to compensate for the less favorable driving force for the oxidative pathway. As a result the latter pathway can compete favorably with the reductive pathway. 

This system illustrates the importance of both the thermodynamic and intrinsic barriers in determining the direction of electron transfer within a given reactant pair. In addition, systems such as the one considered here in which the oxidative and reductive pathways possess comparable rate constants afford an opportunity of controlling or switching the direction of electron transfer by modifying one of the barriers. 

Electronic Structure and Spectroscopic Properties of Molybdenum and Tungsten N2, NNH, NNH2, and NNH3 Complexes with Diphosphine Co-Ligands Insights into the End-on Terminal Reduction Pathway of Di nitrogen Felix Tuczek... 

Table 22.1 Partitioning of aldolization and 1,4-reduction pathways depends critically on the use of cationic Rh-complexes and mildly basic additives.a)...

Maye et al. studied gold nanoparticles supported on carbon black for ORR in both acidic and alkaline media.210 The gold nanoparticles were of a core-shell type where the particle consisted of a gold nanocrystal core of 1-6 nm in diameter that was surrounded by an organic monolayer shell.214 While the Au/C catalyst was found to be active for ORR, its activity was much lower than that of Pt/C, PtRu/C and AuPt/C. The electron transfer in 0.5 M H2S04 was reported as 2.9 0.2, indicating a mixed reduction pathway.210... 

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