Semiempirical Calculations of Nitrated Pyrenes and Their Reduced Metabolites: Relationship to Characteristics of Bioactivation

The bioactivation of mutagenic nitrated polycyclic aromatic hydrocarbons commonly involves the reduction of the nitro moiety, via one- or two-electron steps. We have employed the semiempirical method AM1-CI to calculate the optimized geometries and total energies, adiabatic electron affinities, and heats of formation for a series of nitrated pyrenes, namely 1-nitropyrene and the potently mutagenic dinitropyrenes, 1,3-, 1,6-, and 1,8-dinitropyrene. Adiabatic electron affinities were calculated to estimate the preferential route of reduction. Our results indicate that there is no isomer-specific preference for a one- or two-electron reduction route since the energetics of these nitrated pyrenes are not sufficiently different to explain the isomer preferences observed in biological systems. Other factors such as enzymatic, steric, and rates of autoxidation are likely.