Determination of acid dissociation constants based on continuous titration by feedback-based flow ratiometry

We propose a method for the determination of acid dissociation constants based on the rapid detection of the equivalence point (EP) by feedback-based flow ratiometry and the subsequent estimation of the half equivalence point (EP_1/2). The titrant (e.g., NaOH) flow rate F_B was varied in response to a control voltage V_c from a controller, while the titrand (e.g., CH₃COOH) flow rate F_A was held constant. The pH of the mixed solution was monitored downstream from the confluence point of the solutions following a knotted tubular mixer. Initially, V_c was increased linearly. At the instance the detector sensed EP, the ramp direction of V_c changed downward. The pH increased further because of the lag time between the mixing of solutions and the sensing of pH. Following the pH maximum, the pH decreased. The EP was sensed again in this downward scan. The V_c that gives EP_1/2 was computed from the V_c just at the time of the EP detection. The V_c was held constant at this level for 18 s, and the plateau pH value thus obtained was taken to be the pK_a of the analyte subject to activity corrections. Studies on the dependence of the pK_a on the ionic strength or dielectric constant of the solution were conducted in an automated fashion by delivering NaCl solution or acetonitrile through an additional channel. Satisfactory results were obtained with good throughput (53 s per determination) and precision (R.S.D.≈0.3%) for various acids.