Experimental and theoretical studies of nitrated polycyclic aromatic hydrocarbons

Nitrated polycyclic aromatic hydrocarbons (Nitro-PAHs) constitute a group of mutagenic, carcinogenic and tumorigenic compounds found in particulate matter. They account for about 50% of the mutagenic activity of the diesel emission, thus posing health risks to humans. To predict the mutagenic ability of one nitro-PAH over another, structure-function correlations are important. In this dissertation, answers to the following questions were sought: (i) what predictive structural feature(s) are pertinent in predisposing one nitro-PAH isomer to exhibit more mutagenic, tumorigenic, carcinogenic activity vis-a-vis another? (ii) as major components of the complex matrix of environmental particulates, to what extent are their toxicity effects expressed? (iii) what structure-spectroscopy (13C NMR, UV-Vis, fluorescence and vibrational spectroscopy) correlations exist when the nitro group is at various positions in the aromatic ring?; Investigations of nitro-PAHs of 1--5 benzenoid rings were carried out via experimental and quantum mechanical methods. Insights into the varied nitro-PAH mutagenicities were gained from the widely used density functional theoretical (B3LYP) calculations, and the results compared to experiment. Calculations with various basis sets (6-31G*, 6-311+G**) yielded better, and reliable structural parameters for 1-, 2-nitronaphthalenes, 1-, 2-, 9-nitroanthracenes, 1-, 3-, 4-, 9-nitrophenathrenes, 1-, 2-, 4-nitropyrenes, 6-nitrochrysene than heretofore reported. With quantum mechanical calculations the bond lengths (C-C, C-N, O-N) bond angles, dihedral angles) of 1-, 2-nitronaphthalenes, 1-, 2-, 9-nitroanthracenes, 1-, 3-, 4-, 9-nitrophenanthrenes, 1-, 2-, 4-nitropyrene, 6-nitrochrysene, 1-, 3-, and 6-nitrobenzo[a]pyrene were correlated to observed mutagenic effects in Salmonella typhimurium strains.; The hypothesis proposed by other researchers, namely, the C-C-N-O dihedral angle relative to the aromatic ring as predictive of the mutagenic level of a nitro-PAH within the same PAH, was tested. Our study showed that the mutagenic ability of one nitro-PAH isomers in the same ring may be predicted from its C-C-N-O dihedral relative to the aromatic plane: with planar molecules predicted to be more mutagenic. However, 1-, 2-, and 4-nitropyrene with torsional angles of ∼23°, 0° and 26°, respectively, presented contradictory results based on the hypothesis. We suggest that the nitrated pyrenes undergo different enzymatic reduction routes when interlocking to enzymes (which may be dictated by the D2h symmetry of pyrene). As for studies of 1-, 3-, and 6-nitrobenzo[alpyrenes (1-, 3-, 6-NBaP), predictions suggested results similar to those of nitro-PAHs of naphthalenes, anthracenes, phenanthrenes and chrysene, i.e., 1-, 3-NBaPs are more mutagenic than 6-NBaP and the calculated C-C-N-O dihedral angles of 29°, 30° and ∼60° are predictive of their observed mutagenicity. (Abstract shortened by UMI.)...