Hydroquinone substrates

Vitamin K quinone is reduced to the active hydroquinone substrate for the epoxidase reaction by either a dithiol-linked reductase that is almost certainly the same enzyme as the epoxide reductase or NADPH-dependent quinone reductase, like the epoxide reductase, the dithiol-linked reductase is inhibited by warfarin. In warfarin-resistant rats, there is a warfarin-insensitive epoxide reductase, which also has quinone reductase activity (Hildebrandt et al., 1984 Gardill and Suttie, 1990). 

Rhodamine-labeled hydroquinone substrates 11 were also prepared with the aim of monitoring redox catalysis. H2O2 oxidation to the corresponding benzo-quinones by Cu ions or Cu(II) phenanthroline complexes results in a strong reduction of rhodamine fluorescence [93]. Compound 11 is not suitable as a substrate for SMFS studies with immobilized individual Cu complexes because affinity for... 

Quinones, which become reduced to the corresponding hydroquinones. Two important quinones often used for aromatizations are chloranil (2,3,5,6-tetrachloro-1,4-benzoquinone) and DDQ (2,3-dichloro-5,6-dicyano-l,4-ben-zoquinone). The latter is more reactive and can be used in cases where the substrate is difficult to dehydrogenate. It is likely that the mechanism involves a transfer of hydride to the quinone oxygen, followed by the transfer of a proton to the phenolate ion °... 

Vitamin K is the cofactor for the carboxylation of glutamate residues in the post-synthetic modification of proteins to form the unusual amino acid y-carboxygluta-mate (Gla), which chelates the calcium ion. Initially, vitamin K hydroquinone is oxidized to the epoxide (Figure 45-8), which activates a glutamate residue in the protein substrate to a carbanion, that reacts non-enzymically with carbon dioxide to form y-carboxyglut-amate. Vitamin K epoxide is reduced to the quinone by a warfarin-sensitive reductase, and the quinone is reduced to the active hydroquinone by either the same warfarin-sensitive reductase or a warfarin-insensitive... 

Hydroquinone phosphates (57) transfer phosphate to substrates following... 

Darby JM, DG Taylor, DJ Hopper (1987) Hydroquinone as the ring-fission substrate in the catabolism of 4-ethylphenol and 4-hydroxyacetophenone by Pseudomonas putida Dl. J Gen Microbiol 133 2137-2146. 

A number of mechanistic pathways have been identified for the oxidation, such as O-atom transfer to sulfides, electrophilic attack on phenols, hydride transfer from alcohols, and proton-coupled electron transfer from hydroquinone. Some kinetic studies indicate that the rate-determining step involves preassociation of the substrate with the catalyst.507,508 The electrocatalytic properties of polypyridyl oxo-ruthenium complexes have been also applied with success to DNA cleavage509,5 and sugar oxidation.511... 

M.S. Wilson and R.D. Rauh, Hydroquinone diphosphate an alkaline phosphatase substrate that does not produce electrode fouling in electrochemical immunoassays. Biosens. Bioelectron. 20, 276-283 (2004). 

The organic substrates in Chart 8 can be divided into two main categories in which (i) the oxidation of olefins, sulfides, and selenides involves oxygen atom transfer to yield epoxides, sulfoxides, and selenoxides, respectively, whereas (ii) the oxidation of hydroquinones and quinone dioximes formally involves loss of two electrons and two protons to yield quinones and dinitrosobenzenes, respectively. In order to provide a unifying mechanistic theme for the seemingly disparate transformations in Chart 8, we note that nitrogen dioxide exists in equilibrium with its dimeric forms, namely, the predominant N—N bonded dimer 02N—N02 and the minor N—O bonded isomer ONO—N02 (equation 88). 

The early practical application of antioxidants was connected with the development of rubber production. The rubber is easily oxidized in air, and the first antioxidants were empirically found and used to stabilize it [1]. Empirical search for antioxidants was performed by Moureu and Dufresse [2] during the First World War. These researchers successfully solved the problem of acrolein stabilization by the addition of hydroquinone. They explained the retarding action of the antioxidant in the scope of peroxide conception of Bach and Engler (see Chapter 1). They proposed that the antioxidant rapidly reacts with the formed hypothetical moloxide and in such a way prevents the autoxidation of the substrate. 

It was in 1924 when Christiansen [3] put forward the conception of the chain mechanism of oxidation and explained the action of antioxidants via chain termination by the antioxidant [3]. Three years later, Backstrom and coworkers [4—6] experimentally proved the chain mechanism of benzaldehyde oxidation (see Chapter 1) and the mechanism of antioxidant (hydroquinone) action via chain termination. The systematic study of the oxidation kinetics of esters of nonsaturated acids was performed by Bolland and ten Have [7,8], They observed in the kinetic experiments that substrates are oxidized by the chain mechanism with chain propagation via the cycle of reactions (see Chapter 2). 

Again we see that an alkene isomerisation reaction has taken place. Another important, useful reagent applied in this field is also pictured in Figure 15.7, viz. the use of benzoquinone as the re-oxidant for palladium. Quinone takes the role of dioxygen as oxidising agent. It is very efficient and both quinone and hydroquinone are inert towards many substrates. Furthermore, no water is formed, as is the case when dioxygen is used. 

Validation of the model. Validation of the model was performed using data from rat and mouse liver microsome preparations (Schlosser et al. 1993). The assumption that benzene and its metabolites compete for the same enzyme reaction site was supported in part by the observation of a lag time in the benzene-to-hydroquinone reaction as compared to the phenol-to-hydroquinone reaction. This lag could be explained by the fact that benzene is first hydrolyzed to phenol, which is then hydrolyzed to hydroquinone, and if all compounds are substrates for P-450 2E1, the kinetics of this pathway would be slowed compared to those of the direct phenol-to-hydroquinone pathway. The model also adequately predicted phenol depletion and concomitant hydroquinone formation resulting from phenol incubations. 

Qrunones can accept one or two electrons to form the semiquinone anion (Q ") and the hydroquinone dianion (Q ). Single-electron reduction of a quinone is catalyzed by flavoenzymes with relatively low substrate selectivity (Kappus, 1986), for instance NADPH cytochrome P-450 reductase (E.C. 1.6.2.3), NADPH cytochrome b5 reductase (E.C. 1.6.2.2), and NADPH ubiquinone oxidoreductase (E.C. 1.6.5.3). The rate of reduction depends on several interrelated chemical properties of a quinone, including the single-electron reduction potential, as well as the number, position, and chemical characteristics of the substituent(s). The flavoenzyme DT-diphorase (NAD(P)H quinone acceptor oxidoreductase E.C. 1.6.99.2) catalyzes the two-electron reduction of a quinone to a hydroquinone. 

To elucidate some enzymatic characteristics of the isolated laccases I, II, and III, substrate specificities for several simple phenols, electrophoresis patterns, ultraviolet spectra, electron spin resonance spectra, copper content, and immunological similarities were investigated. Tyrosine, tannic acid, g c acid, hydroquinone, catechol, pyrogallol, p-cresol, homocatechol, a-naphthol, -naphthol, p-phenylenediamine, and p-benzoquinone as substrates. No differences in the specificities of these substrates was found. The UV spectra for the laccases under stucfy are shown in Figure 4. Laccase III displays three adsorption bands (280, 405, and 600nm), laccase II shows one band 280nm), and laccase I shows two bands (280 and 405 nm). These data appear to indicate differences in chemical structure. The results of the copper content analysis (10) and two-dimensional electrophoresis also indicate that these fractions are completely different proteins (10), Therefore, we may expect differences in substrate specificities between the three laccase fractions for more lignin-like substrates, yet no difference for some simple phenolic substrates. 

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