Naphthalene, dihydrodiol

Initially formed polar metabolites such as phenols and amines may be conjugated to water-soluble terminal metabolites that are excreted into the medium and function as an effective mechanism of detoxification. For example, pentachlorophenol and pentachlorothiophenol produced from pentachloronitrobenzene conjugated represented the major metabolites. Although the naphthalene dihydrodiol was the major metabolite produced from naphthalene, the further transformation... 

Patel TR, DT Gibson (1974) Purification and properties of (+)-cZ5-naphthalene dihydrodiol dehydrogenase of Pseudomonas putida. Bacteriol 119 879-888. 

On the contrary, the m-benzenedihydrodiol is found to react 4500 times more rapidly in the presence acid than the trans. Moreover, as shown below, this ratio falls to 440 for naphthalene dihydrodiols, to 50 for phenanthrene dihydrodiols, and less than 10 for a nonaromatic analog such as the acenaphthylene or dihydronaphthalene dihydrodiols.164 These rate ratios are shown on the following page and suggest that the effect is linked to the aromaticity of the ultimate product of the reaction. Trapping experiments with the 10-hydroxyphenanthrenonium ion 31 indicate that the ratio of... 

Naphthalene may adversely affect the eye, causing cortical cataracts and retinal degeneration.11 These affects are attributed to the naphthalene dihydrodiol metabolite (see the product of reaction 13.6.3). 

The naphthalene dihydrodiol dehydrogenase NahB from P. putida strain G7 has been purified as the his-tagged enzyme, and shown to catalyze also the dehydrogenation of biphenyl-2,3-dihydrodiol. biphenyl-3,4-dihydrodiol, and 2,2, 5,5 -tetrachlorobiphenyl-3,4-dihydrodiol (Barriault et al. 1998). In addition, 1,2-dihydroxynaph-thalene dioxygenase carried out extradiol fission of 3,4-dihydrox-ybiphenyl at both the 2,3- and 4,5-positions. 

Figure 1. Catabolic pathways for degradation of naphthalene by bacteria. I, naphthalene II, cis-l,2-dihydro-l,2-dihydroxynaphthalene (naphthalene dihydrodiol) III, l,2-dihydrox3maphthalene IV, 2-hydroxy-chromene-2-carboxylate V, mns-o-hydroxybenzyIidene pyruvate VI, salicylaldehyde Vn, salicylate VIII catechol IX, c 5,ci8-muconate semialdehyde X, cis,ci8-muconate XI, gentisate XII, maleylpyruvate.

Multistep biocatalysis for the preparation of optically pure epoxides was applied by Sello and coworkers [24, 25]. The commercially available 3-vinyl benzaldehyde was the substrate of choice for the synthesis of 3-(oxiran-2-yl) benzoic acid in high yields and optical purity by solely employing enzyme catalysis (Scheme 3.6). This goal was achieved by applying a mixed culture approach with different recombinant E. coli strains expressing, individually, both oxidizing biocatalysts. One strain contained a native ADH and a SMO from Pseudomonas Jiuorescens ST, while a second one expressed a naphthalene dihydrodiol dehydrogenase (NDDH) from P. Jiuorescens N3. 

The bacterial aerobic degradation of pyrene is initiated by the formation of cfi-pyrene-4,5-dihydrodiol. Analysis for this metabolite was used to demonstrate the biodegradability of pyrene in an environment in which there was continuous input of the substrate, when it was not possible to use any diminution in its concentration as evidence for biodegradation (Li et al. 1996). The corresponding metabolite from naphthalene—cfi-naphthalene-1,2-dihydrodiol—has been used to demonstrate biodegradation of naphthalene both in site-derived enrichment cultures and in leachate from the contaminated site (Wilson and Madsen 1996). 

Althongh the degradation of naphthalene-2-carboxylate by Burkholderia sp. strain JT 1500 involves the formation of 1-hydroxy naphthalene-2-carboxylate, this is not formed from the expected (l/ ,25)-di-l,2-dihydrodiol-2-naphthoate. Possibly, therefore, the reaction is carried out by a monooxygenase, or a dehydration step is involved. Subsequent reactions produced pyruvate and o-phthalate that was degraded via 4,5-dihydroxyphthalate (Morawski et al. 1997). Degradation of naphthalene carboxylates formed by oxidation of methyl groups has already been noted. 

A cytochrome P450 has been purified from Saccharomyces cerevisiae that has benzo[a]pyrene hydroxylase activity (King et al. 1984), and metabolizes benzo[fl]pyrene to 3- and 9-hydroxybenzo[fl]pyrene and benzo[fl]pyrene-7,8-dihydrodiol (Wiseman and Woods 1979). The transformation of PAHs by Candida Upolytica produced predominantly monohydroxyl-ated products naphth-l-ol from naphthalene, 4-hydroxybiphenyl from biphenyl and 3- and 9-hydroxybenzo[fl]pyrene from benzo[fl]pyrene (Cerniglia and Crow 1981). The transformation of phenanthrene was demonstrated in a number of yeasts isolated from littoral sediments and of these, Trichosporumpenicillatum was the most active. In contrast, biotransformation of benz[fl]anthracene by Candida krusei and Rhodotorula minuta was much slower (MacGillivray and Shiaris 1993). 

The presence of metabolites determined from laboratory experiments of degradation pathways. Examples inclnde (a) di-dihydrodiols of PAHs in a marine sediment (Li et al. 1996) and naphthalene in leachate from a contaminated site (Wilson and Madsen 1996),... 

Roubal et al. (8) applied TLC to the separation and identification of metabolites of l c-iabeled naphthalene administered to coho salmon fingerlings via intraperitoneal injection. 1-Naphthol, a dihydrodiol, mercapturic acid, 1-naphthyl glucuronic acid and a glycoside/sulfate fraction were identified in brain, liver, gall bladder, and muscle 1-naphthol, a dihydrodiol, and 1-naphthyl glucuronic acid were the only metabolites found in heart. 

Collier et al. (10) demonstrated that HPLC was an effective technique for the separation of aromatic hydrocarbon metabolites in exposed marine organisms. Radioactive bioconversion products were studied in liver and gall bladder of coho salmon dosed with H-naphthalene. Quantitative identifications of glucuronide, sulphate, dihydrodiol, glycoside, and 1-naphthol derivatives were obtained. Three additional polar compounds of unknown structure were found. A typical HPLC profile is shown in Figure 2. 

HPLC studies on the brain of mature rainbow trout revealed essentially four metabolites, including the dihydrodiol and 1-naphthol (12). No evidence was found for the presence of conjugated derivatives. It was concluded that the conjugated derivatives of naphthalene were excluded by blood-brain barrier systems that develop in mature organisms. 

Recent studies in our laboratories have shown that newly hatched herring (Clupea harengus pal Iasi) larvae exposed to purififed 3H-naphthalene in seawater at concentrations of 10 ppb for 9 hr accumulated a variety of conjugated and non-conjugated metabolites. HPLC analysis indicates the presence of the parent compound as well as three additional compounds whose retention times are consistent with a sulfate, a dihydrodiol, and 1-naphthol (Fig. 3). 

Like for benzene, the cytotoxicity of naphthalene is not due to the epoxide but to the quinone metabolites, namely 1,2-naphthoquinone and 1,4-naphthoquinone [85], As shown in Table 10.1, naphthalene 1,2-oxide (10.2) is a better substrate than benzene oxide for epoxide hydrolase. Its rapid isomerization to naphthalen-l-ol, facile enzymatic hydration to the dihydrodiol and lack of reactivity toward nucleophiles such as glutathione may explain its absence of direct toxicity [85],... 

Fig. 10.9. Stereoselective formation of the 1,2-dihydrodiols of naphthalene and anthracene from their precursor 1,2-oxides, 10.2 and 10.24, respectively (modified from [86])... 

P. J. van Bladeren, J. M. Sayer, D. E. Ryan, P. E. Thomas, W. Levin, D. M. Jerina, Differential Stereoselectivity of Cytochrome P450b and P450c in the Formation of Naphthalene and Anthracene 1,2-Oxides. The Role of Epoxide Hydrolase in Determining the Enantiomer Composition of the 1,2-Dihydrodiols Formed ,. /. Biol. Chem. 1985, 260, 10226- 10235. 

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