Formation of Peroxide and a Reversible Oxidation-Reduction in Solutions of Sulfanilamide

Abstract

In accordance with a previous concept of the mechanism of sulf-hemoglobin formation I investigated whether sulfanilamide which often causes sulfhemoglobinemia forms H2O2 in presence of molecular oxygen. Aqueous solutions of sulfanilamide were prepared in different concentrations. The phenolphthalin reagent and, as a catalyst, copper sulfate, both as described by Schales, were added. Oxygen was bubbled through the solutions. Parallel controls contained distilled water instead of sulfanilamide solution. The development of a red color resulting from the oxidation of phenolphthalin into phenolphthalein under the given conditions is specific for the presence, which implies the formation of hydrogen peroxide or labile peroxides. Concentrations of H2O2 as low as 1:10 are detectable by means of this method. In solutions containing sulfanilamide in a concentration of 250 mg per 100 cc and more the formation of H2O2 was regularly found. In lower concentrations, e. g., 100 mg per 100 cc, no convincing specific effect was detectable. From the failure to find H2O2 in the less concentrated solutions one could conclude that possibly not the sulfanilamide itself but rather some other substance accompanying the drug as an impurity might be responsible for the H2O2 formation as described above. Two facts make such a presumption improbable but do not entirely exclude it. (1) There could not be found any characteristic differences in the behavior of different preparations of sulfanilamide. (2) Neither could there be found any shift in the limit after purifying the drug by recrystallization. Thus the formation of H2O2, although under the given experimental conditions in a rather slight amount, seems to be due to the sulfanilamide itself. That makes it likely that in vivo by means of any catalyst present, H2O2 can be formed from an oxidation of sulfanilamide.