Experimental and theoretical studies of nitrated polycyclic aromatic hydrocarbons

by 1966- Onchoke, Kefa Karimu

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-à-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 ii 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[a]pyrenes (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. To experimentally gain further insights into the nitro-PAH’s physical-chemical properties and the nitro group’s influence and electronic effects, synthesized 1-, 3- and 6- nitrobenzo[a]pyrenes were characterized by UV-Vis, 1H/13C NMR, fluorescence, FT-IR iii and FT-Raman spectroscopies. The detailed vibrational spectroscopy was necessary for obtaining the spectra necessary for trace environmental analysis. Structure-function correlations as well as spectroscopic signatures were necessary for these mononitrated isomers. Detailed infrared and Raman spectroscopic data for benzo[a] pyrene and its mononitrated BaPs were provided for the first time. By utilizing density functional theory (B3LYP/6311+G**), the molecular geometries and vibrational spectra were calculated. There was noted good agreement between the calculated and experimental geometry for BaP, and predictions of the nitrated compounds were within ~ 5 cm-1.The geometrical distortions of BaP structure upon nitro group substitution and correlations between structural parameters and vibrational data as well as structure-function relationships related to the mutagenicity of this important class of polycyclic aromatic hydrocarbons were provided. From other studies, nitro orientation trends were found to closely follow the photophysical property trends. Nitro-PAHs whose nitro group was non-planar to the aromatic plane tended to exhibit higher quantum yields (?f), and in general closely resembled the parent PAH absorption bands. TDDFT simulation of the excitation states was found to corroborate the observation. Similarly, the ?PAH ring? ?*PAH ring singlet excitations mainly predominated in nitro-PAHs with a non-planar nitro group. Observed effects of the nitro group upon the observed UV-vis, NMR, fluorescence, and vibrational spectroscopy were correlated to known mutagenic effects. iv