THE SPIROCHETICIDAL AND TRYPANOCIDAL ACTION OF ACIDSUBSTITUTED PHENYL ARSENOXIDES AS A FUNCTION OF pH AND DISSOCIATION CONSTANTS

¹ Venereal Disease Research Laboratory of the U. S. Public Health Service, the Johns Hopkins Hospital, Baltimore-5, Maryland

1. The trypanocidal and spirocheticidal activity of most of the acid-substituted phenyl arsenoxides here studied increased strikingly with increasing hydrogen ion concentration in the pH range 5.5-9.0.

2. This was due to the fact that the ionized salts of these compounds were only a fraction as active as the undissociated free acids, which had a uniform molar activity approximating that of unsubstituted phenyl arsenoxide.

3. The relative activity of an acid-substituted phenyl arsenoxide at a given pH was therefore roughly predictable from a) the proportions of ion and free acid, determined by the pK of the substituent group, and b) the varying molar activity of the ion. As anticipated, strongly acidic compounds, yielding no significant amounts of free acid even at pH 5.0, failed to show the usual pH effect.

4. The relative inactivity of the salts of these compounds reflected the fact that they were bound by the trypanosomes to only a minor degree, while the undissociated free acids, like all highly active compounds, were concentrated as much as three hundred-fold. Variations in pH, affecting the relative proportions of ions and free acid, similarly affected the degree to which a given arsenical was bound by the trypanosomes.

5. The question as to whether the undissociated free acids are more strongly bound because of a greater reactivity with cellular constituents, or whether they differ from the ionized salts primarily in their ability to penetrate into the interior of the cell, is discussed in the text. The weight of evidence is in favor of the latter view.

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