Synthesis and Biological Activity of Metabolites of Environmental Nitroarenes

Abstract

Nitroarenes are released into the environment from combustion processes; many compounds of this class are potent mutagens, and some may be carcinogens. The oxygenated derivatives of nitroarenes may be formed through atmospheric transformations of nitroarenes; as metabolites of the nitroarenes in biological systems these may be the species that mediate biological effects in vivo. We describe here efficient and convenient routes for preparation of individual nitropyrenol, acetamidopyrenol, nitrofluoranthenol and acetamidofluoranthenol isomers in high purity and good yields, and a comparison of their potency in the Ames plate incorporation assay. The synthetic approach was based on functionalization of the aromatic nucleus by acetylation or benzoylation, directed where necessary by selective desaturation of the aromatic moiety, followed by conversion to the corresponding ester and nitration. Rigorous purification was carried out before or after hydrolysis of the ester, based on the ease of separation of the esters compared to the phenols. Pyrene derivatives substituted at the 1 and 6 positions and the 1 and K-region positions were strongly mutagenic, while hydroxylation at other positions on the aromatic periphery decreased activity. 3-Nitrofluoranthen-8-ol was the most potent of the hydroxylated fluoranthene derivatives.

Key words::

• Nitroarenes
• nitropyrenols
• nitrofluoranthenols
• acetamidopyrenols
• acetamidofluoranthenols
• synthesis
• mutagenicity