KINETICS AND MECHANISMS OF ACTION OF DRUGS ON MICROORGANISMS .8. QUANTIFICATION AND PREDICTION OF BIOLOGICAL ACTIVITIES OF META- AND PARA-SUBSTITUTED N1-PHENYLSULFANILAMIDES BY MICROBIAL KINETICS

The apparent Ihsi-onler generation rate Constanta, kapp, were deiermined in the steady-state growth of Escho-ichia coli in presence of graded concentrations, S, of a series of systematically substituted Ni-phenylsulfanilamides. From the expression kapp = k0kbS/(1 + kbS), where G is the determined generation rate constant in absence of drug, the bacteriostatic activity parameters, kb, in 1. μmole-1, were calculated. A good linear relationship was obtained between log k1 values and modified Hammett substituent parameters, p = 1.12 ± 0.11, with the exception of the parent compound and the N1-3,.5-dinitrophenylsulfanilamide. A systematic dependency of k1 values on pH in the range of 6.0-7.4, where k0 was constant, was not observed. The kapp values obtained in t he presence of sulfonamide when extrapolated to zero drug concentration yielded calculated values for k0 that showed dependence on pH. The activity parameters were independent of the determined chloroform-water distribution coefficients and applications of these data to the Hanseh equation did not improve lhe correlation of G, with substituent constants. © 1969, American Chemical Society. All rights reserved.