Structure-Mutagenicity Correlation of Nitrated Pyrenes Calculated by Molecular Orbital Method.

The mutagenic activity of nitrated pyrenes (NPs) depends largely on the number and the position of the nitro group. To elucidate the differences in the mutagenicity, we performed molecular orbital calculations for seven NPs, their metabolic intermediates, and their DNA adducts. The extension of the investigation to the metabolites provided no significant improvement. The heats of formation, however, of NP-DNA adducts were correlated with the mutagenicity; the DNA model was composed of five base pairs with the sequence of guanine-thymine-guanine-guanine-guanine and nitrenium ions of NPs as an ultimate mutagen were bonded at the C8 position of the middle guanine. A plot of the heats of formation against the logarithms of the mutagenic activity showed a good linearity with a correlation coefficient of −0.85. The results suggest that the stability of the NP-DNA is an important factor to determine the mutagenicity of NPs. [ABSTRACT FROM PUBLISHER]