Quinone-mediated Reactions

Reduction of monocyclic aromatic nitro compounds has been demonstrated (a) with reduced sulfur compounds mediated by a naphthoquinone or an iron porphyrin (Schwarzenbach et al. 1990), and (b) by Fe(II) and magnetite produced by the action of the anaerobic bacterium Geobacter metallireducens (Heijman et al. 1993). Quinone-mediated reduction of monocyclic aromatic nitro compounds by the supernatant monocyclic aromatic nitro compounds has been noted (Glaus et al. 1992), and these reactions may be signihcant in determining the fate of aromatic nitro compounds in reducing environments (Dunnivant et al. 1992). 

As already discussed in chapter 4, reactive intermediates can react with reduced GSH either by a direct chemical reaction or by a GSH transferase-mediated reaction. If excessive, these reactions can deplete the cellular GSH. Also, reactive metabolites can oxidize GSH and other thiol groups such as those in proteins and thereby cause a change in thiol status. When the rate of oxidation of GSH exceeds the capacity of GSH reductase, then oxidized glutathione (GSSG) is actively transported out of the cell and thereby lost. Thus, reduced GSH may be removed reversibly by oxidation or formation of mixed disulfides with proteins and irreversibly by conjugation or loss of the oxidized form from the cell. Thus, after exposure of cells to quinones such as menadione, which cause oxidative stress, GSH conjugates, mixed disulfides, and GSSG are formed, all of which will reduce the cellular GSH level. 

Flavins are very versatile redox coenzymes. Flavopro-teins are dehydrogenases, oxidases, and oxygenases that catalyze a variety of reactions on an equal variety of substrate types. Since these classes of enzymes do not consist exclusively of flavoproteins, it is difficult to define catalytic specificity for flavins. Biological electron acceptors and donors in flavin-mediated reactions can be two-electron acceptors, such as NAD+ or NADP+, or a variety of one-electron acceptor systems, such as cytochromes (Fe2+/ Fe3+) and quinones, and molecular oxygen is an electron acceptor for flavoprotein oxidases as well as the source of oxygen for oxygenases. The only obviously common aspect of flavin-dependent reactions is that all are redox reactions. 

Some derivatives with mediating properties are suitable to form chemically modified electrodes (CMEs) with catalytic properties for NADH oxidation (55). Various attempts have been tried with different classes of mediators to immobilize the mediator onto solid electrodes or in carbon paste electrodes since the first deliberately made CME for electrocatalytic oxidation of NADH was described by Tse and Kuwana in 1978 (56), see Table I. They and others (67-72) based their CMEs on immobilized ortho-quinone derivatives. However, these CMEs were rapidly inactivated in the presence of NADH, probably because of side reactions in the catalytic process (72). For some other immobilized mediators one major reaction route could be proposed as the CME turned out to be quite stable in the presence of NADH. The catalytic reaction sequence comprizes two steps, one chemical between NADH and the immobilized mediator (reaction (6)) and one electrochemical between the mediator and the electrode (reaction (7)). The sequence is given below for the simplest case ... 

Studies on metabolic stability using hepatocyte suspensions are not feasible for automation/HTS, but these studies do provide rather complete profiles of hepatic biotransformation without the supplements of cofactors and cosubstrates. The use of S9 in metabolic stability studies can be evaluated in a manner similar to that used for the microsomal assays, but with the possible addition of a broader panel of cofactors or cosubstrates. These include NADPH for CYP/FMO-mediated reactions, NADH for xanthine oxidoreductase and quinone oxidoreductase 2, NADPH-dependent reductions by carbonyl reductases, and NADPH/NADH-dependent reductions catalyzed by aldo-keto reductases, uridine 5 -diphosphate... 

The Friedel-Crafts reaction, a widely used reaction in both industrial and academic laboratories, produces several byproducts which must be handled as pollutants. An alternative which involves the photochemically-mediated reaction of an aldehyde with a quinone is described. This alternative chemistry can be applied to direct syntheses of the ring systems of the benzodiazepines and benzoxepins. 

An even more direct route would evolve from the connection of the two reagents shown below. Interestingly, the photochemically mediated reaction of a quinone with an imine has never been reported. If we can identify suitable reaction conditions for this transformation, we will have secured an exceptionally direct route to the benzodiazepine ring system. The imine required for this reaction has been previously synthesized and can readily be generated in multigram quantities by the condensation of benzaldehyde with the N-methyl amide of glycine. Even though the... 

Transient absorption spectroscopy has been used to study isolated Photosystem 2 (PS2) reaction centres stabilised by the use of anaerobic conditions. In the absence of added artificial electron donors and acceptors, the light induced electron transfer properties of the reaction centre are restricted to the formation of the radical pair P680+Pheophytin and charge recombination pathways from this state [1]. This charge recombination has been observed to produce a 23% yield of a chlorophyll triplet state [1]. Attempts to reconstitute these particles with quinone have until now been limited to the observation of a steady state, quinone-mediated photoreduction of the cytochrome b-559 [2]. 

Although the broad rate/-AG°et dependences exhibited by the quinone-mediated electron transfers are suggestive of the coupling of high frequency, internal cofactor modes [8,13], and calculated FC factors for organic redox centers indicate a possib e contribution of 0.1-0.3 eV to X [28,29], our results demonstrate that if there are distinct contributions from internal modes of the cofactors to X, they are not sufficiently different to cause a measurable effect on the rateZ-AG et profile. This suggests that small-molecule redox centers include a set of modes with a comparable distribution of frequencies that can be coupled to the reaction. This is consistent with the general... 

The surface EE mechanism shows that the current brings about the reversible surface-redox reaction of the quinone mediator (is) and is written as follows ... 

LY311727 is an indole acetic acid based selective inhibitor of human non-pancreatic secretory phospholipase A2 (hnpsPLA2) under development by Lilly as a potential treatment for sepsis. The synthesis of LY311727 involved a Nenitzescu indolization reaction as a key step. The Nenitzescu condensation of quinone 4 with the p-aminoacrylate 39 was carried out in CH3NO2 to provide the desired 5-hydroxylindole 40 in 83% yield. Protection of the 5-hydroxyl moiety in indole 40 was accomplished in H2O under phase transfer conditions in 80% yield. Lithium aluminum hydride mediated reduction of the ester functional group in 41 provided the alcohol 42 in 78% yield. 

Humic acid and the corresponding fulvic acid are complex polymers whose structures are incompletely resolved. It is accepted that the structure of humic acid contains oxygenated structures, including quinones that can function as electron acceptors, while reduced humic acid may carry out reductions. These have been observed both in the presence of bacteria that provide the electron mediator and in the absence of bacteria in abiotic reactions, for example, reductive dehalogenation of hexachloroethane and tetrachloromethane by anthrahydroquininone-2,6-disulfonate (Curtis and Reinhard 1994). Reductions using sulfide as electron donor have been noted in Chapter 1. Some experimental aspects are worth noting ... 

Reactions of partial electrochemical oxidation are of considerable interest in the electrosynthesis of various organic compounds. Thus, at gold electrodes in acidic solutions, olefins can be oxidized to aldehydes, acids, oxides, and other compounds. A good deal of work was invested in the oxidation of aromatic compounds (benzene, anthracene, etc.) to the corresponding quinones. To this end, various mediating redox systems (e.g., the Ce /Ce system) are employed (see Section 13.6). 

Later, Torii et al. found that the tin-aluminum-mediated allylation can be carried out with the less expensive allyl chloride, instead of allyl bromide, when a mixture of alcohol-water-acetic acid was used as the solvent.77 When combined with stoichiometric amounts of aluminum powder, both stoichiometric and catalytic amounts of tin are effective. As reported by Wu et al., higher temperatures can be used instead of aluminum powder.78 Under such a reaction condition, allyl quinones were obtained from 1,4-quinones, followed by oxidation with ferric chloride. Allylation reactions in water/organic solvent mixtures were also carried out electrochemically, with the advantage that the allyltin reagent could be recycled.79... 

The initial oxidation of the flavanol components of fresh leaf to quinone structures through the mediation of tea polyphenol oxidase is the essential driving force in the production of black tea. While each of the catechins is oxidizable by this route, epigallocatechin and its galloyl ester are preferentially oxidized.68 Subsequent reactions of the flavonoid substances are largely nonenzymic. 

Field JA, Cervantes FJ (2005) Microbial redox reactions mediated by humus and structurally related quinones. In Perminova IV, Hatfield K, Hertkom N (eds) Use of humic substances to remediate polluted environments from theory to practice, vol 52. Springer, Dordrecht, pp 343-352... 

Redox mediators, such as flavins or quinones, are usually involved in the azo bond reduction. Therefore, the azo bond cleavage is a chemical, unspecific reaction that can occur inside or outside the cell, relying on the redox potential of the redox mediators and of the azo compounds. Also the reduction of the redox mediators can be both a chemical and an enzymatic process. As a consequence, it is an evidence that environmental conditions can affect the azo dyes degradation process extent both directly, depending on the reductive or oxidative status of the environment, and indirectly, influencing the microbial metabolism. 

As hydroxyl or hydroxyl-like radicals are produced by the superoxide-driven Fenton reaction, superoxide overproduction must also occur in thalassemic cells. First, it has been shown by Grinberg et al. [382], who demonstrated that thalassemic erythrocytes produced the enhanced amount of superoxide in comparison with normal cells in the presence of prooxidant antimalarial drug primaquine. Later on, it has been found that the production of superoxide and free radical-mediated damage (measured through the MetHb/Hb ratio) was much higher in thalassemic erythrocytes even in the absence of prooxidants, although quinones (menadione, l,4-naphthoquinone-2-methyl-3-sulfonate) and primaquine further increased oxidative stress [383]. Overproduction of superoxide was also observed in thalassemic leukocytes [384]. 

---