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

Abstract

Many phthalate esters (PAEs) are chemicals of high production volume and of toxicological concern. Second-order rate constant for base-catalyzed hydrolysis (kB) is a key parameter for assessing environmental persistence of PAEs. However, kB for most PAEs are lacking, and experimental determination of kB encounters various difficulties. Herein, density functional theory (DFT) methods were selected by comparing empirical kB values of 5 PAEs and 5 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 (kB_side chain), quantitative structure-activity relationship (QSAR) models were developed. The models can differentiate PAEs with departure of leaving-group (or nucleophilic attack of OH‾) as the rate-determining step in the hydrolysis, and estimate kB values, which provides a promising way to predict hydrolysis kinetics of PAEs. Half-lives of the investigated PAEs were calculated and vary from 0.001 hours to 558 years (pH = 7 ~ 9), further illustrating the necessity of prediction models for hydrolysis kinetics in assessing environmental persistence of chemicals.