Oxidative dechlorination

In contrast to oxidative dechlorination, the hydrolytic dechlorination of chloramphenicol replaces a Cl-atom with a OH group to yield a (monochlo-ro)hydroxyacetamido intermediate. The latter, like the dichloro analogue, also eliminates HC1, but the product is an aldehyde that is far less reactive than the oxamoyl chloride intermediate. Chloramphenicol-aldehyde undergoes the usual biotransformation of aldehydes, namely reduction to the primary alcohol 11.41 and dehydrogenation to the oxamic acid derivative 11.40 (Fig. 11.7). 

Pathways for the genotoxicity PCP are outlined in Scheme 15. In the presence of cytochrome P450, PCP undergoes oxidative dechlorination to form tetrachloroben-zoquinone (TCBQ) that reacts with dG and other DNA bases to form benzetheno-type adducts. ° ° Activation by enzymes with peroxidase activities furnishes the... 

Ukrainczyk, L., and M.B. McBride. 1993. The oxidative dechlorination reaction of 2,4,6- trichlo-rophenol in dilute aqueous suspensions of manganese oxides. Environ. Toxicol. Chem. 12, 2005-2014. 

No metabolism has been demonstrated for the decachlorobiphenyl (NI0SH, ref. 136, p. 29). This and other highly chlorinated PCBs not readily metabolized may persist in the tissues for years following exposure. Some PCBs lacking the adjacent hydrogens required for rapid metabolism can be slowly metabolized by hydroxylation and oxidative dechlorination. Since arene oxide intermediates may also be involved, there is the risk of chronic exposure to compounds of high carcinogenic activity (ref. 136, p. 30). 

Studies in rodents and in human liver cells have shown that pentachlorophenol is metabolized by oxidative dechlorination to tetrachlorohydroquinone and tetrachloro-l,4-benzoquinone ... 

Chloramphenicol and secobarbital exhibit properties similar to those of tienilic acid, but they have not been studied in humans (11). Oxidative dechlorination of chloramphenicol with formation of reactive acyl chlorides appears to be an important metabolic pathway for irreversible inhibition of CYP. Chloramphenicol binds to CYP, and subsequent substrate hydroxylation and product release are not impaired. The inhibition of CYP oxidation and the inhibition of endogenous NADPH oxidase activity suggest that some modification of the CYP has taken place, which inhibits its ability to accept electrons from the CYP reductase (11). Secobarbital completely inactivates rat CYP2B1 functionally, with partial loss of the heme chromophore. Isolation of the N-alkylated secobarbital heme adduct and the modified CYP2B1 protein revealed that the metabolite partitioned between heme N-alkylation, CYP2B1 protein modification, and epoxidation. A small fraction of the prosthetic heme modifies the protein and contributes to the CYP2B1 inactivation (12). 

Figure 5. Summary of the biotransformations of dieldrin. These involve hydroxylation, hydration, oxidative dechlorination, and reductive dechlorination (39, 42, 65).

Ferrari RP, Laurenti E, Trotta F (1999) Oxidative dechlorination of 2, 4, 6-trichlorophenol catalyzed by horseradish peroxidase. J Biol Inorg Chem 4 232-237... 

Chlorinated Pesticides. The major metabolic degradation pathways for toxaphene in all organisms are probably reductive dechlorination and reductive dehydrochlorination. In some cases, oxidative dechlorination has been observed to result in hydroxy derivatives, acids and ketones.76 Aldrin is transformed into dieldrin in biotic as well as abiotic transformation processes. 

A final example of oxidative dehalogcnation concerns the antibiotic chloramphenicol. In vitro studies have shown that the dichloroacetamide portion of the molecule undergoes oxidative dechlorination to yield a chemically reactive oxa-myl chloride intermediate that can react with water to form... 

N-oxidation/S-oxidation Dihydroxylation Dehydrogenation or reduction Demethylation Deethylation Depropylation Oxidative deamination Oxidative dechlorination Oxidative defluorination Hydration Methyl to an acid Conjugation Glucuronidation Sulfation... 

The antibiotic chloramphenicol is oxidized by cytochrome P-450 monooxygenase to chloramphenicol oxamyl chloride formed by the oxidative dechlorination of the dichloromethyl moiety of chloramphenicol. The reactive metabolite binds to the e-amino group of a lysine residue in the cytochrome P-450 (Fig. 32.6). This yields an adduct that blocks the electron transport from NADPH cytochrome P-450 reductase. This type of mechanism is termed a suicide-substrate mechanism. 

Reductions Microbial and mammalian nitroreductase reduces nitro compounds to amines. Chlorinated alkanes and alkenes are common contaminants in ground water and chlorinated aromatics, PCBs, organochlorine pesticides, are often detected in soils and sediments and it has been of interest to evaluate the potential for these compounds to be metabolized. A number of microorganisms are able to dechlorinate both halogenated aliphatic and aromatic compounds in a reduction reaction." It has been observed that the more highly chlorinated congeners are more reactive in these systems in contrast to the response in oxidative dechlorinations. 

Govindaraj, N., M. M. Mortland, and S. A. Boyd. 1987. Single electron transfer mechanism of oxidative dechlorination of 4-chloroanisole on copper(II)-smectite. Environ. Sci. Technol. 21 1119-1123. 

Additionally, electrochemical transformations may occur when the contaminants enter into the anode or the cathode, particularly chlorinated organic compounds, which are shown to undergo reductive dechlorination at the cathode and oxidative dechlorination at the anode. Such transformations should also be considered based on the redox conditions in the electrodes and the contaminant characteristics. 

Lu S, Huang J, Peng Z, Li X, Yan J. BaU milling 2,4,6-trichlorophenol with calcium oxide dechlorination experiment and mechanism considerations. Chem Eng J 2012 195-196 62-8. 

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