ELECTROCHEMICAL STUDIES OF SOLUTION KINETICS. THE THEORY AND PRACTICE OF CHRONOAMPEROMETRY, WITH APPLICATION TO THE MECHANISM OF ACETAMINOPHEN TOXICITY

A system for the collection an analysis of kinetic data from a computer-controlled, thermostatted pulse electrochemical instrument is fully described, including all aspects of the electronics, hardware, and software. The theory of potentiodynamic, hydrostatic electrochemical experimentation, especially double- and single-step chronoamperometry (DSCA, SSCA), is presented in depth. The influence of homogeneous kinetics is examined, with subsequent development of models based on simultaneous partial differential equations. Methods of effecting solution are considered. A new method of approximate numerical solution called orthogonal collocation (OC) is developed from first principles. The advantages, limitations, and applications of OC are discussed, and several novel kinetic schemes and experiment geometries are solved. This system has been applied to the study of the hydrolysis of proposed drug metabolite N-acetyl-p-quinoneimine (NAPQI). Rate constants are measured by DSCA as a function of pH, temperature, and buffer concentration. This data, and cyclic voltammetry, is used to formulate a precise mechanism, establish lifetimes, and determine activation energies. The relative rates of 1,4 (Michael) addition of several sulfhydryl nucleophiles is measured by SSCA. Results are discussed in light of possible toxicologic implications. Further applications of this system are proposed