Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced in the combustion of fossil fuels, tobacco, and other organic matter. Some PAHs are potent carcinogens and mutagens that present a major health hazard to human populations. While the chemistry, environmental occurrence, and mechanisms of carcinogenesis of alternant PAHs, such as benzo[a]pyrene, have been extensively investigated and are moderately well understood, the opposite is true for the equally large class of nonalternant PAHs. Moreover, studies in these areas are severely hampered by the relative unavailability of nonalternant PAHs of authentic structure from commercial sources and the deficiency of synthetic methods for their preparation. The long range goal of this research program is to elucidate the role of nonalternant PAHs as environmental carcinogens and contribute to understanding of their mechanisms of carcinogenesis. This project is directed toward development of novel, general synthetic approaches to several major classes of nonalternant PAHs that occur as environmental contaminants. These include: (1) polycyclic fluoranthenes, (2) cyclopenta-fused PAHS, (3) polycyclic fluorenes, (4) methylene-bridged PAHs, and (5) their methyl-substituted derivatives (expected to be more carcinogenic) and other derivatives (e. g. the methylene-bridged ketones). It is also proposed to synthesize a representative series of each class of PAHs (12-14 compounds) on preparative scale. Each of these compounds will be obtained pure and will be fully characterized by NMR, UV, and other methods. These PAHs will be made available to other investigators as standards for environmental analysis and for investigations of their biological properties. It is also planned to conduct mutagenic assays of all new PAHs as a preliminary probe of their potential carcinogenic properties. The greater accessibility of nonalternant PAHs likely to result from this project will provide major impetus for research on the chemistry and biological properties of these types of PAHs which may lead ultimately to greater understanding of the role of nonalternant PAHs in human cancer.
