pH Dependency in Uptake of Sulfonamides by Bacteria

Abstract

Sulfonamide-sensitive cells of Escherichia coli were incubated under standardized conditions with various sulfonamides and the quantity of sulfonamide uptake into the bacteria measured. The test substances reached a higher concentration inside the bacteria than in the incubation medium, the degree of accumulation varying for the individual substances despite uniformly applied incubation conditions. In all cases a pH dependency was detected which varied with the pK_a values of the substances tested. On the basis of the pK_a dependency of the pH effect, the sulfonamide uptake can be interpreted as being a passive diffusion process. Knowing the intracellular pH value, which was determined by the DMO method, it was then possible to calculate the theoretically expected value for the accumulation as a concentration coefficient. Since the calculated and experimentally determined values differ approximately by a factor of 2, an intracellular binding of the sulfonamides is assumed. The same results were obtained in cells of sulfonamide-resistant E. coli strains.

Lipoamide Channel-Binding Sulfonamides Selectively Inhibit Mycobacterial Lipoamide Dehydrogenase

“…Prontosil proved to be a prodrug that was metabolized to an active sulfonamide. Later studies suggested that sulfonamides enter bacteria via passive diffusion in a manner governed in part by the pK a of the compound and the extracellular-intracellular pH gradient (27, 28). All sulfonamide antibiotics currently in use, such as sulfisoxazole, sulfadiazine, sulfacetamide, sulfamethoxazole and sulfadoxine, have pK a values ranging from 5.0 to 6.5.…”

“…Prontosil proved to be a prodrug that was metabolized to an active sulfonamide. Later studies suggested that sulfonamides enter bacteria via passive diffusion in a manner governed in part by the p K a of the compound and the extracellular–intracellular pH gradient. , All sulfonamide antibiotics currently in use, such as sulfisoxazole, sulfadiazine, sulfacetamide, sulfamethoxazole, and sulfadoxine, have p K a values ranging from 5.0 to 6.5. In contrast, the most basic of the predicted p K a values of the sulfonamide compounds reported here range from 11.77 to 13.00, but because of their amphoteric nature, they are predicted to exist mostly as noncharged molecules at physiological pH and thus would be expected to enter by passive diffusion.…”

Influence of pH on the toxicity of ionisable pharmaceuticals and personal care products to freshwater invertebrates

“…Moreover it considers dissociation of the chemical inside the organisms due to a difference between the pH of the exposure medium and the internal pH of the organisms, leading to an ion trap effect. According to Büttner and Büttner (1980), the relationship between the internal concentration of the neutral chemical form and the external concentration can be formulated as:…”