On the role of solvent in acid-base equilibria of diuretics in acetonitrile-water mixed solvents

The dissociation constants of representative loop (furosemide), thiazide (chlorthiazide and trichlormethiazide) and potassium sparing (amiloride) diuretics in 10, 30, 40, 50 and 70% (w/w) acetonitrile-water mixtures at 298.15 K were determined, in accordance with IUPAC procedures. The variation in pK(a) values over the whole composition range can be explained by preferential solvation and the structural features in acetonitrile-water mixtures. Correlations between pK(a) values and various bulk and solvatochromic properties of the solvents were calculated. The linear solvation energy relationship (LSER) method was applied. The resulting equations allowed us to calculate pK(a) values for the diuretics studied in any acetonitrile-water mixture up to 70% (w/w) and should help to clarify the acid-base behaviour of diuretics in the widely-used acetonitrile-water mixed solvents.