Aminofluorene oxidation

Table IV. The effect of pH on the nature of the products formed by aminofluorene oxidation.

Boyd JA, Eling TE (1984) Evidence for a one-electron mechanism of 2-aminofluorene oxidation by prostaglandin H synthase and horseradish peroxidase. J Biol Chem 259 13885-13896... 

Phenobarbital, trans stilbene oxide, 2-acetyl aminofluorene Various, including phenobarbital... 

Schemes 24 and 34. Not all specific examples follow these generalized pathways. Although 78h does decompose predominately into 99 (Scheme 44) at neutral pH, evidence suggests that it may not do so via an addition-elimination mechanism. This intermediate is detectable in reaction mixtures, but it has never been isolated due to its high reactivity. The N-benzoyl analogue 78h has been prepared by anodic oxidation of N-benzoyl-2-aminofluorene and has been shown by labeling experiments to generate 99 by an intramolecular pathway presumably involving the intermediate 100. ...

Prostaglandin synthetase, peroxidase or lipid peroxidation have been shown to oxidise arylamine xenobiotics to reactive species that bind extensively to DNA. The binding could be an initial event in the toxic or carcinogenic process. Evidence is presented that cation radicals are involved in the formation of the various oxidation products and DNA adduct formation with the carcinogen aminofluorene. Furthermore methylaminoazobenzene (butter yellow) was found to form the same major GSH adduct as is formed in vivo. 

DNA binding during aminofluorene catalyzed oxidation by peroxide... 

TABLE II. DNA OR POLYRIBONUCLEOTIDE ADDUCT FORMATION WITH AMINOFLUORENE FOLLOWING OXIDATION BY PEROXIDES... 

Azofluorene formation was decreased if the reacting mixture contained DNA. Two other products decreased by the presence of DNA was a band (Rf 0.31) II which turned brown-green within several hours of running the plate and a band (Rf 0.48) I which turned blue-green after running the plate. Ascorbate was needed to be added to the reaction mixture before extraction to observe band I. This suggests that I unlike II is fully oxidised in the reaction mixture. Oxidation of both products by H202 and peroxidase resulted in the rapid formation of the same transient blue intermediate as was observed with aminofluorene. Product I however bound much more rapidly to DNA than Product II and unlike Product II could not be removed from the DNA by extraction with 1% sodium dodecyl sulfate. Product II showed... 

We previously compared the properties of the reactive species involved in DNA binding by N-OH-aminofluorene, N-acetoxy-acetyl-aminofluorene and the aminofluorene products formed by a peroxidase catalyzed oxidation (28). The marked differences in reactivity suggested that different species were involved and that nitrenium ions were not responsible for the peroxidase catalyzed activation. The identity of the products formed following a peroxidase catalyzed oxidation is still not clear. Other investigators have shown the formation of nitrofluorene and azofluorene but most of the... 

Fig. 5.15 Initial products formed in the oxidation of aminofluorene by HRP. Further oxidative products can occur under the continued catalytic action of the peroxidase...

Dehydrogenation A-Demethylation Hydroxylation Epoxidation Sulfoxidation Oxidations Acetaminophen, benzidine, DES, epinephrine Dimethylaniline, benzphetamine, aminocarb Benzo[a]pyrene, 2-aminofluorene, phenylbutazone 7,8-Dihydrobenzo[a]pyrene Methylphenylsulfide FANFT, ANFT, bilirubin Esterases and Amidases Paraoxon, dimethoate, phenyl acetate Epoxide Hydrolase Benzo(a)pyrene epoxide, styrene oxide DDT-Dehydrochlorinase p,p- DDT Glutathione Reductase Disulfiram... 

The sludge of zinc dust and zinc oxide is filtered from the boiling solution and extracted (Note 3) with 50 cc. of boiling 78 per cent alcohol. The combined filtrates are then poured into 2 1. of water, whereupon a white, flocculent precipitate is obtained. This is filtered with suction and recrystallized from 400 cc. of hot 50 per cent alcohol. The purified 2-aminofluorene crystallizes in needles melting at 127.5°. The yield is 26-21 g. (78-80 per cent of the theoretical amoxmt). 

The promutagen 2-aminofluorene (29) was activated to an unknown mutagenic compound by exposure to sunlight oxygen was required for activity. Mixtures of oxidized nitrogen species were suggested to be the active agents (White and Heflich,... 

Floyd. R. A., Soong. L. M., and Culver, P. L. Horseradish peroxidase/ hydrogen peroxide-catalyzed oxidation of the carcinogen M-hydroxy-Af-acetyl-2-aminofluorene as affected by cyanide and ascorbate. Cancer Res.. 36 1510-1519.1976. 

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