Ionization of Sulfonamides

Abstract

A recent quantitative analysis of bacteriostasis by sulfanilamide, sulfapyridine, sulfadiazine and sulfathiazole showed that for inhibition of Es. coli decreasing amounts of each drug in the order named were required. 1 Actually over six hundred times more sulfanilamide is required than sulfathiazole or sulfadiazine, and similar results have also been obtained with a variety of other microörganisms, 2 indicating that this regular increasing order of bacteriostatic potency is characteristic of these N₁ sulfonamides (Col. A, Table I) and not attributable to the selective action of one drug against a certain organism. Furthermore, the quantitative relationships between these sulfonamides and para aminobenzoic acid (PAB) differ just as widely; e. g., over 600 times more PAB is needed to block sulfathiazole and sulfadiazine than to block sulfanilamide. (Col. F.) When the minimum effective concentration of each drug was tested, the same amount of PAB was required to block each drug. (Col. E.) In other words, going from sulfanilamide to sulfadiazine a progressively larger proportion of each drug actually present in the cultures appears to possess activity against either bacteria or PAB; the active moiety presumably being similar for each drug.

It seems possible that such a partition into active and inactive portions might be controlled by the extent to which the drugs are ionized in the cultures. Accordingly the dissociation constants were measured∗ (Col. B) and the percent of each drug ionized at pH 7.0 (Col. C) was computed. (Some shift in the apparent pK may be expected to occur in complex biological media.) Based on these values and using the minimum effective amounts of drug added to the culture (Col. A), the concentration of ionized drug was estimated (Col. D).