SPECTROELECTROCHEMICAL EXAMINATION OF THE REACTIONS OF CHLORPROMAZINE CATION RADICAL

摘要

The decay of electrogenerated chlorpromazine cation radical (CPZ('+(.))) was studied using glancing incidence reflection spectroelectrochemistry. The buffer catalyzed hydrolysis of CPZ('+(.)) was investigated with phosphate and carboxylate nucleophiles. The overall form of the reaction was demonstrated to be a half regeneration mechanism with the final products being CPZ sulfoxide and reduced precursor. Rate constants for this reaction were measured in the pH range 2 through 9. The rate of reaction for several monofunctional nucleophiles such as acetate, dihydrogen phosphate, and dihydrogen citrate were comparible, while those of select polyfunctional nucleophiles were much faster. An explanation for this effect, based on the proximity of two radicals attached to a single nucleophile, was presented.;In addition, the reduction of chlorpromazine cation radical by various catecholamines was examined. Rate constants for this electron transfer reaction were measured and an overall reaction mechanism proposed. The simultaneous oxidation of both CPZ and the catecholamines at the electrode, coupled with optical monitoring of the reaction intermediates offers a number of advantages studies of electron transfer reactions using electrochemistry. Two of these advantages are particularly noteworthy. First, the optical monitoring of the reaction intermediates precludes the necessity of having only one of the electron transfer pair electrochemically active. This greatly expands the number of compounds amenable to electrochemical analysis of their homogeneous electron transfer reactions. Second, the time scale of these solution electron transfer reactions was increased as a result of reactant dilution by electrochemical removal. This expansion in reaction time permitted the use of slower electrochemical techniques to monitor the reaction intermediates.;Finally, in answer to the pharmacological activity of chlorpromazine, semiquantitative studies were perfomed on the competitive reactions between CPZ('+(.)) and nucleophilic or reducing agents. Based on these results postulations were made about the fate of CPZ('+(.)) in the physiological environment.