BIOACTIVATION INVOLVING CHEMICALLY REACTIVE OXYGENATED CARBON

Abstract

The most thoroughly studied bioactivations involving oxygenated carbon are those leading to the formation of epoxidized xenobiotics. Although epoxides are often thought of as electrophilicly reactive mutagens and toxins which attack biological nucleophiles, only a very few epoxides present such a risk. The chemical reactivity of epoxides varies dramatically as evidenced by the compounds discussed below. In each case, the epoxidized xenobiotic has greater biological activity that the corresponding alkene. Epoxidation of aldrin leads to the more biologically active dieldrin. The resulting epoxide is so stable that dieldrin is considered a persistent pesticide. The epoxidation of farnesoic acid or methyl farnesoate leads to the greatly enhanced biological activity of insect juvenile hormone. The epoxide of juvenile hormone is sufficiently biodegradable to present no residue problem. On the other hand it is not sufficiently reactive to cause concern as an alkylating agent. Neither of the above two compounds owe their biological activity to the chemical reactivity of the epoxide moiety. On the other hand, precocene epoxide is exceptionally reactive, and its biological activity may stem from this reactivity. It is possible that a mutagen, toxin or carcinogen may be formed as a result of metabolism or environmental degradation of a pesticide. No severe problems involving dangerously reactive epoxides have surfaced in the pesticide field. However, the mutagenic potency of compounds such as the aflatoxins and polycyclic aromatics point to a potential hazard which must be appreciated during pesticide development. If chemical reactivity is considered in the broadest sense, a number of oxidative bioactivations have proved useful in pest control. Some of these are discussed below.