Prediction Models on pKa 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 pK(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 pK(a) and k(B) values were measured experimentally. A semiempirical quantum chemical (QC) method was selected to calculate pK(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 pK(a) and k(B) values, quantitative structure-activity relationships with determination coefficients (R-2) being 0.947 and 0.842 for the pK(a) and k(B) models, respectively, were developed, which were validated and could be employed to efficiently fill the k(B) and pK(a) data gaps of parabens within applicability domains. The base-catalyzed hydrolysis half-lives were estimated to range from 6 h to 1.52 x 10(6) years (pH 7-9, 25 degrees 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.

Automated summary

The study experimentally measured the pK(a) and k(B) values of six parabens, established quantitative structure-activity relationship models to fill the data gaps, and estimated the base-catalyzed hydrolysis half-lives range.