Oxidation and reduction process for polycyclic aromatic hydrocarbons and nitrated polycyclic aromatic hydrocarbons

Epoxidation is the first metabolic activation step necessary for polycyclic aromatic hydrocarbons (PAHs) to exert their biological activity. Nitrated polycyclic aromatic hydrocarbons (NPAHs) may undergo nitro reduction or ring oxidation, or a combination of ring oxidation and nitro reduction. We used density functional theory at the B3LYP/6-31+G**//B3LYP/6-31G* level of theory to explore both the reduction of NPAHs and epoxidation of PAHs and NPAHs. Substituent effects on the stability of nitrobenzene and its derivatives generated in the process of the nitro reduction were investigated. Two linear (free) energy relationships were observed: (1) a correlation between the enthalpy difference DeltaH0meta [Delta H0 = H0 (meta) - H0 (para)] and the charge differences on the carbon bonded to the reaction site for neutral molecules; and (2) a correlation between the DeltaH0meta and the Hammett substituent constant difference Deltasigma (Deltasigma = sigmam - sigmarho). We also explored substituent and solvent effects on the reduction, and linear Hammett correlations were obtained. The effects of ring systems on the reduction thermodynamics were also examined. Larger ring systems and azaheterocycles were found to be generally more feasibly reduced than the parent nitrobenzene system. The thermochemistry of the epoxidation reactions of various PAHs and NPAHs were explored. The regioselectivities of the epoxidations were found to be consistent with the available experimental data. We also investigated the isomerization process for arene oxides, derived from both PAHs and NPAHs, to form the corresponding oxepines. The calculated results quantitatively demonstrate the facility and the feasibility of the isomerization at room temperature. The results reveal the significant effect of the aromaticity changes on the isomerization. By comparing the results for NPAHs with the results for PAHs, the effect of the nitro group on the isomerization was found to be dependent on the location of the oxirane and the structure of the NPAH. The calculations also reveal that solvation effects on the isomerization of the NPAH oxides are different from and more complex than that of the parent PAH oxides. Our results elucidate the origin of the racemization of the optically active arene oxides.