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

Acid-base equilibria in ethanol-aqueous solution of 5-acetamido-1,3,3-thiadiazole-2-sulfonamide (acetazolamide, H(2)acm), 5-tertbutyloxycarbonylamido-1,3,4-thiadiazole (B-H(2)ats), 5-amino-1,3,3-thiadiazole-2-sulfonamide (Hats) and 5-amino-1,3,4-thiadiazole-2-thiol (Hatm) at 25 degrees C, 0.15 mol dm(-3) ionic strength (NaNO3), 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(2)ats, pk(a1) = 7.33(3) and pk(a2) = 9.27(1); Hats, pk(a1) = 2.51(3) and pk(a2) = 8.49(1); Hatm, pk(a1) = 1.92(1) and pk(a2) = 6.81(1); whereas the constants determined by spectrophotometry were: H(2)acm, pk(a1) = 7.78(1) and pk(a2) 9.57(2); B-H(2)ats, pk(a1) = 7.71(2) and pk(a2) = 9.61(2); Hats, pk(a1) = 2.19(3) and pk(a2) = 8.61(2); Hatm, pk(a2) = 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-K(2)ats in which the first deprotonation takes place at the carbonamido group. (C) 1999 Elsevier Science B.V. All rights reserved.