Synthesis and Biological Activity of A Series of Nitrated Cyclopenta-Fused Polycyclic Aromatic Hydrocarbons
Public Deposited- Last Modified
- February 28, 2019
- Creator
-
Goldring, Jay M.
- Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
- Abstract
- In order to test current hypotheses of nitroarene-induced mutagenesis, a series of nitrated cyclopenta-fused isomers of benzanthracene and pyrene (Fig.4) were synthesized and their mutagenic activities toward Salmonella typhimurium were evaluated in the Ames plate incorporation assay. Current theories state that endogenous enzymes present in bacterial and mammalian cells activate nitroarenes via reduction to hydroxylamines which can be converted upon protonation or conjugation to nitrenium ions which are the postulated active chemical species. Thus mutagenic activity should be correlated with both the "ease of reduction" of the compound as well as the stability of the postulated arylnitrenium ion. The theoretical "ease of reduction" of the nitrated polycyclic aromatic hydrocarbons (PAH) in this study was determined by calculating lowest unoccupied molecular orbital (LUMO) energies (Klopman et al., 1984); our results indicate that they should be readily reduced by the nitroreductase enzymes. Huckel molecular orbital calculations indicate that the nitrenium ions should also be exceptionally stable compared to other nitroPAH. Thus these compounds are anticipated to be active mutagens whose activity should parallel the stability of the nitrenium ions. However, while these compounds do produce significant numbers of revertants in the Ames assay, they are not nearly as active as some of the more potent nitroarenes. Reasons for this relative lack of activity are discussed and modifications in the above mentioned theories are proposed.
- Date of publication
- August 1986
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Turner, Alvis G.
- Gold, Avram
- Kamens, R. M.
- Degree
- Master of Science in Public Health
- Academic concentration
- Environmental Management and Policy
- Degree granting institution
- University of North Carolina at Chapel Hill
- Graduation year
- 1986
- Language
- Deposit record
- 4229e0fb-b010-4ede-aa50-9d4a2f0726fb
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