Anomalous salting-out, self-association and pKa effects in the practically-insoluble bromothymol blue.

Abstract

The widely-used and practically insoluble diprotic acidic dye, bromothymol blue (BTB), is a neutral molecule in strongly acidic aqueous solutions. The Schill (1964) extensive solubility-pH measurement of bromothymol blue in 0.1 and 1.0 M NaCl solutions, with pH adjusted with HCl from 0.0 to 5.4, featured several unusual findings. The data suggest that the difference in solubility of the neutral-form molecule in 1M NaCl is more than 0.7 log unit lower than the solubility in pure water. This could be considered as uncharacteristically high for a salting-out effect. Also, the study reported two apparent values of pKa1, 1.48 and 1.00, in 0.1 M and 1.0 M NaCl solutions, respectively. The only other measured value found for pKa1 in the literature is -0.66 (Gupta and Cadwallader, 1968). It was reasoned that the there can be only a single pKa1 for BTB. Also, it was hypothesized that salting-out alone might not account for such a large difference in solubility observed at the two levels of salt. A generalized mass action approach incorporating activity corrections for charged species using the Stokes-Robinson hydration equation and for neutral species using the Setschenow equation, was selected to analyze the Schill solubility-pH data to seek a rationalization of these unusual results. BTB reveals complex speciation chemistry in saturated aqueous solutions which had been poorly understood for many years. The appearance of two different values of pKa1 at different levels of NaCl and the anomalously high value of the empirical salting-out constant could be rationalized to normal values by invoking the formation of a very stable neutral dimer (log K2 = 10.0 ± 0.1 M-1). A 'normal' salting-out constant, 0.25 M-1 was then derived. It was also possible to estimate the 'self-interaction' constant. The data analysis in the present study critically depended on the pKa1 = -0.66 reported by Gupta and Cadwallader. A more reasonable salting-out constant and a consistent single value for pKa1 have been determined by considering a self-interacting (aggregation) model involving an uncharged form of the molecule, which is likely a zwitterion, as suggested by literature spectrophotometric studies.