N-Acetyl-p-benzoquinone imine is an important toxic metabolite of acetaminophen and phenacetin, two common analgesics. Certain ring-substituted derivatives of this material are also toxins. Although there is considerable speculation concerning the mechanism of action of this and related quinone imine derivatives, there is little detailed knowledge of the chemistry of these compounds on which to base such conjectures. We have commenced a study of the chemistry of N-acetyl-p-benzoquinone imine and related compounds. Our study is concerned with the mechanisms of the generation of the quinone imine from its assumed precursors in phenacetin metabolism, its hydrolysis reactions and its reactions with Lewis bases in an aqueous environment, and its redox chemistry. We are employing kinetic methods which involve the use of UV spectrophotometry and HPLC to characterize these reactions. Product studies are also being carried out in an effort to understand the chemistry of this material. We are also using cyclic voltammetry and ESR methods to detect possible radical intermediates that may be involved in its redox reactions. We expect that the results of this study will provide a more sound basis for understanding the in vivo activity of N-acetyl-p- benzoquinone imine, and the ways in which it may be generated in biological systems.
