The Possible Rôle of Ionization in the Bacteriostatic Action of the Sulfonamides *

One of the most pronounced differences between the commonly used sulfonamide drugs lies in their acid strength. Since the compounds, in general, seem to increase in 25 50 75 bacteriostatic efficacy in vitro as they show s IONIZED an increase in this quality, it seemed of I interest to determine what evidence, if pH any, could be gathered to support the 2 hypothesis that part, at least, of the differences in bacteriostatic potency can be SA 3 attributed to the varying degrees of ionization of the substances in question. Fildes' believes that bacteriostatic sub4 stances block some essential enzyme, and AB the hypothesis suggested above would 13 5 demand that the ions of these substances react with the ions of the enzyme, here 6 considered to be largely in dissociated form. It follows from these assumptions 7 that the various drugs of this class be equally bacteriostatic at equi-ionic concentrations. 8 Accordingly, the approximate ionization constants of some sulfonamides, as 9 well as of sulfanilic acid, were determined by titration with NaOH, using the glass s 10 electrode. From these constants, ionization curves were calculated, as well as the G fractions ionized at pH levels of 6.0, 6.8, and 7.6, since this pH range includes the zone in which most bacterial growth can Ia readily take place. The results are inIONIZATION CURVES cluded in the figure and in Table 1. It OF is obvious that the fractions of the variSULFONAMIDES ous drugs present as ions at the common