Prediction Models on p K a and Base-Catalyzed Hydrolysis Kinetics of Parabens: Experimental and Quantum Chemical Studies

Parabens for which the molecules contain hydrolytic and ionizable groups, are emerging pollutants due to their ubiquity in the environment. However, lack of p K a and second-order base-catalyzed hydrolysis kinetics ( k B ) values limits their environmental persistence assessment. Herein, six parabens were selected as reference compounds for which the p K a and k B values were measured experimentally. A semiempirical quantum chemical (QC) method was selected to calculate p K a of the parabens, and density functional theory (DFT) methods were selected to calculate k B for neutral and anionic forms of the parabens, by comparing the QC-calculated and determined values. Combining the QC-calculated and experimental p K a and k B values, quantitative structure–activity relationships with determination coefficients ( R 2 ) being 0.947 and 0.842 for the p K a and k B models, respectively, were developed, which were validated and could be employed to efficiently fill the k B and p K a data gaps of parabens within applicability domains. The base-catalyzed hydrolysis half-lives were estimated to range from 6 h to 1.52 × 10 6 years (pH 7–9, 25 °C), further necessitating the in silico models due to the tedious and onerous experimental determination, and the huge number of hydrolyzable and ionizable chemicals that may be released into the environment.