INTERACTION OF TRACE METALS WITH PHENOTHIAZINE DRUG DERIVATIVES, II. FORMATION OF FREE RADICALS

Abstract

Absorption spectrometry, oxidimetric titrations, electrolysis, and electron spin resonance spectrometry served to identify as a semiquinone free radical ion the chromophore produced from chlorpromazine and its congeners by some metal ions and other univalent electron acceptors. Some interactions leading to the formation and disappearance of the radical ions were described. Two concurrent reactions were encountered while defining the complete bivalent oxidoreduction sequence from the native drugs via semiquinone intermediates to the respective fully oxidized products a probable dimerization of the reduced chlorpromazine and a tautomerization of the bivalently oxidized quininoid form to the sulfoxide, the latter step being irreversible under the mild reaction conditions of the forward reactions. A spontaneous dismutation of the free radical also was documented under conditions wherein the radical was not stabilized by concentrated acid.