A potentiometric and spectrophotometric study on acid–base equilibria in ethanol-aqueous solution of acetazolamide and related compounds

Abstract

Acid–base equilibria in ethanol-aqueous solution of 5-acetamido-1,3,4-thiadiazole-2-sulfonamide (acetazolamide, H 2acm), 5-tertbutyloxycarbonylamido-1,3,4-thiadiazole-2-sulfonamide (B-H 2ats), 5-amino-1,3,4-thiadiazole-2-sulfonamide (Hats) and 5-amino-1,3,4-thiadiazole-2-thiol (Hatm) at 25°C, 0.15 mol dm −3 ionic strength (NaNO 3), have been investigated by potentiometry and UV spectrophotometry. The ionization constants were calculated with SUPERQUAD program from potentiometric measurements and by a method according to Edsall et al. using the mole fractions determined by complementary tri-stimulus colorimetry (CTS). The constants obtained by potentiometry were: B-H 2ats, p k a 1 =7.33(3) and p k a 2 =9.27(1); Hats, p k a 1 =2.51(3) and p k a 2 =8.49(1); Hatm, p k a 1 =1.92(1) and p k a 2 =6.81(1); whereas the constants determined by spectrophotometry were: H 2acm, p k a 1 =7.78(1) and p k a 2 =9.57(2); B-H 2ats, p k a 1 =7.71(2) and p k a 2 =9.61(2); Hats, p k a 1 =2.19(3) and p k a 2 =8.61(2); Hatm, p k a 2 =6.90(2). Theoretical calculations using MO semiempirical and ab-initio RHF/6-31G* computations for the compounds were also performed. It was possible to clarify the preferred deprotonation mechanism of acetazolamide and B-H 2ats in which the first deprotonation takes place at the carbonamido group.