Paul G. Seybold

Explorations of Structure-Property Relations

Departments of Chemistry and Biochemistry, Wright State University, Dayton, Ohio 45435 USA.

Three molecular structure-property studies will be discussed as illustrations of different approaches to the problem of the relationship between chemical structure and toxicological action.

The first approach will examine the value of simple molecular orbital calculations in understanding the carcinogenic activities of polycyclic aromatic hydrocarbons and their derivatives. Molecular orbital calculations of the presumptive activation steps and species for these compounds (via the "bay region activation theory") yield a surprisingly good guide to the observed carcinogenic activities. This same approach also helps to explain the varied activities observed for the methyl derivatives of these compounds, some of which display greatly enhanced carcinogenicity and others of which display reduced carcinogenicity or no carcinogenic activity. Application to the observed pattern of deactivation caused by hydroxyl substitution will also be discussed.

The second study will review structure-property work on the tissue solubilities of halogenated hydrocarbons. Multiple regression analysis using simple ad hoc descriptors gives a reasonably clear account of the factors influencing the solubilities of these compounds in blood, muscle, fat, and liver tissue. With the aid of principal component analysis, it is shown that there are two dominant dimensions to this problem, which can be interpreted in terms of solubilities of the compounds in lipid (e.g., olive oil) and saline solutions.

The third study will discuss the value of using more than one descriptor set to analyze a structure-property relationship. The boiling points of alcohols will be used as an illustration to reach the (perhaps surprising) conclusion that a theoretical model can sometimes be more accurate that the data upon which it is based. Moreover, two models are better than one.

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