Development of Prediction Models on Base-Catalyzed Hydrolysis Kinetics of Phthalate Esters with Density Functional...

Many phthalate esters (PAEs) are chemicals of high production volume and of toxicological concern. The second-order rate constant for base-catalyzed hydrolysis ( k_B) is a key parameter for assessing environmental persistence of PAEs. However, the k_B values for most PAEs are lacking, and the experimental determination of k_B encounters various difficulties. Herein, density functional theory (DFT) methods were selected by comparing empirical k_B values of five PAEs and five carboxylic acid esters with the DFT-calculated ones. Results indicate that PAEs with cyclic side chains are more vulnerable to base-catalyzed hydrolysis than PAEs with linear alkyl side chains, followed by PAEs with branched alkyl side chains. By combining experimental and DFT-calculated second-order rate constants for base-catalyzed hydrolysis of one side chain in PAEs ( k_{B_side chain}), quantitative structure-activity relationship models were developed. The models can differentiate PAEs with the departure of the leaving group (or the nucleophilic attack of OH^-) as the rate-determining step in the hydrolysis and estimate k_B values, which provides a promising way to predict hydrolysis kinetics of PAEs. The half-lives of the investigated PAEs were calculated and vary from 0.001 h to 558 years (pH = 7∼9), further illustrating the necessity of prediction models for hydrolysis kinetics in assessing the environmental persistence of chemicals.