Activation of the carcinogen N-hydroxy-N-(2-fluorenyl)benzamide via chemical and enzymic oxidations. Comparison to oxidations of the structural analog N-hydroxy-N-(2-fluorenyl)acetamide
| Autor: | Richard W. Decker, Clare L. Ritter, Danuta Malejka-Giganti |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
chemistry.chemical_classification
biology Chemistry Stereochemistry Substrate (chemistry) Hydroxyacetylaminofluorene Nitroxyl General Medicine Toxicology Medicinal chemistry High-performance liquid chromatography Horseradish peroxidase chemistry.chemical_compound Enzyme Carcinogens biology.protein Benzene Benzamide Oxidation-Reduction Biotransformation Chromatography High Pressure Liquid Horseradish Peroxidase Acetamide Peroxidase |
| Zdroj: | Chemical Research in Toxicology. 5:520-527 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx00028a010 |
| Popis: | Chemical or enzymatic oxidations of the carcinogen N-hydroxy-N-(2- fluorenyl)benzamide (N-OH-2-FBA) were investigated under the conditions facilitating one-electron oxidation or oxidative cleavage of N-hydroxy-N-(2-fluorenyl)acetamide (N-OH-2-FAA). HPLC methods were developed for separation and quantitation of the above hydroxamic acids and their respective oxidation products. To identify the products of oxidation of N-OH-2-FBA, N-(benzoyloxy)-2-FBA (N-BzO-2-FBA) was synthesized and shown to undergo ortho rearrangement to 1- and 3-BzO-2-FBA. Oxidation of N-OH-2-FBA (4.88 mM) with alkaline K3Fe(CN)6 in benzene was complete and yielded equimolar amounts of 2-nitrosofluorene (2-NOF) and the ester (chiefly N-BzO-2-FBA), indicative of one-electron oxidation to nitroxyl free radical which undergoes bimolecular dismutation. However, one-electron oxidation of N-OH-2-FBA (30 or 10 microM) by horseradish peroxidase/H2O2 at pH 7 or myeloperoxidase/H2O2 at pH 6.5 yielded only approximately 10% as much product as N-OH-2-FAA (30 microM). The addition of 0.1 mM Br- +/- 0.1 M Cl- at pH 4 to 6.5 increased 2-NOF formation in MPO/H2O2-catalyzed oxidations. Simulations of these oxidations with HOCl/Cl- or HOBr/Br- showed that the latter was more efficient, converting N-OH-2-FAA almost completely and less than or equal to 62% of N-OH-2-FBA to 2-NOF. The amounts of the ester (N- and o-BzO-2-FBA), which by itself did not contribute to 2-NOF formation or significant substrate regeneration, indicated that approximately 10% of 2-NOF originated from one-electron oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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