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. 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.

IsPETase- and IsMHETase-Catalyzed Cascade Degradation Mechanism toward Polyethylene Terephthalate

“…The QM/MM calculation was carried out on the ChemShell platform, combined with TURBOMOLE (dealing with the QM region) and DL-POLY program (dealing with the MM region) with the CHARMM27 force field to generate the optimized structure and QM/MM energy. The QM region was treated by the DFT method, − and the MM region was treated by the CHARMM27 force field. In the calculation of QM/MM, the linking hydrogen atom method, charge shift model, and electrostatic embedding scheme were used.…”

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

“…Previous studies investigated the effects of side chain type (alkyl or aryl) on hydrolysis kinetics of PAEs and organophosphate triesters, and also indicated that the aryl side chains are more vulnerable to the base-catalyzed hydrolysis than the alkyl side chains. 23,59 The current study further unveils the effects of side chain length on the base-catalyzed hydrolysis kinetics of the parabens.…”

“…The integral equation formalism of the polarized continuum model (IEFPCM) 49 and SMD 40 were widely used implicit solvation models and have been testified with good performance in many studies on hydrolysis. 23,25,27,28 These two implicit solvation models were initially tested for the reference compounds as well. Effects of explicit water molecules on the hydrolysis kinetics were also evaluated.…”

“…28 Xu et al adopted DFT to calculate k B values of 25 phthalate esters (PAEs), and developed quantitative structure−activity relationship (QSAR) models that can be employed to predict the base-catalyzed hydrolysis kinetics of PAEs. 23 To the best of the authors knowledge, there is no available QSARs or in silico tools that can be employed for predicting the base-catalyzed hydrolysis kinetics of parabens that have ionizable groups.…”

“…The k h , k B_PB , k B_PB – , and p K a values can be determined by experiments as well as quantum chemical calculation, for example, density functional theory (DFT) and high level complete basis set (CBS) methods. , Some parabens may have very long t 1/2 values, rendering the experimental determination of the hydrolysis kinetics tedious. Unavailability of authentic chemical standards for some parabens also limits the experimental determination.…”