Quantum Chemical Computation And QSAR Models On Hydrolysis Rates Of Phthalate Esters And Parabens

Hydrolysis rate constant(kh)is a key parameter for assessing the environmental persistence of chemicals.The kh value usually relates to the contribution of acid-catalyzed,neutral,and base-catalyzed hydrolysis.For most of chemicals,base-catalyzed hydrolysis is dominant.However,the kh values are lacking.It is not realistic to experimentally measure the h values for their environmental persistence assessment,due to the high time cost and unavailability of some chemical standards.Therefore,it is necessary to develop methods for predicting the kh values.In this study,experimental measurement and quantum chemical calculation were employed to unveil hydrolysis pathways of phthalate esters(PAEs)and parabens.Furthermore,hydrolysis kinetic parameters were calculated,and quantitative structure-activity relationship(QSAR)models were developed for predicting kh values.Main research contents and results are as follows:(1)Prediction methods and models on second-order rate constant for base-catalyzed hydrolysis(kB)of PAEs were developed.PAEs are chemicals of high production volume,and only five PAEs have experimental kB values.In this study,by comparing experimental kB and density functional theory(DFT)calculated values,appropriate DFT method was selected.The selected DFT method was employed to predict kB of the other 20 PAEs.Multiple linear regression(MLR)method was employed to develop QSAR models.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 kB values.Results indicate that hydrolysis of PAEs follows the order:PAEs with cyclic side chains>PAEs with linear alkyl side chains>PAEs with branched alkyl side chains.The calculated hydrolysis half-lives(t1/2)vary from 0.001 hours to 558 years(pH=7～9,25℃),which solves the problem in evaluating the environmental persistence of PAEs due to lack of hydrolysis kinetic parameters.(2)Prediction models for kB of phthalate monoesters(MPEs)were developed.MPEs are primary hydrolysis product of PAEs,and have been widely detected in the environment.In this study,DFT method was employed to unveil base-catalyzed hydrolysis pathways of MPEs and calculate their kB values.MLR method was employed to establish QSAR model for predicting kB of MPEs.Results indicate that the smaller is the acidity constant(pKa)of alcohol leaving groups,the faster is the hydrolysis kinetics of MPEs.The developed model provides a tool that can be used to predict kinetics of complete hydrolysis of two carboxylic esters in PAEs.(3)Prediction methods and models on hydrolysis kinetic parameters of parabens were established.Parabens for which the molecules contain hydrolyzable and ionizable groups,are emerging pollutants because of their ubiquity in the environment.Parabens in the aquatic environments have different dissociation forms,which influence their base-catalyzed hydrolysis kinetics.In this study,six parabens with available chemical standards were selected as reference compounds for which pKa and kB values were measured experimentally.A semiempirical quantum chemical(QC)method was selected to calculate pKa of the parabens,and DFT methods were selected to calculate kB for neutral and anionic forms of the parabens,by comparing the QC calculated and determined values.Combining the QC-calculated and experimental pKa and kB values,QSAR models were developed.Results indicate that t1/2 values of PBs range from 6 hours to 1.52 × 106 years(pH 7～9,25 ℃).This study efficiently fills the kB and pKa data gaps of parabens.(4)Prediction program that can be employed to predict hydrolysis kinetic parameters of PAEs,MPEs and parabens was preliminarily written.In this study,calculation process and method of the prediction program were designed.Prediction models that can realize prediction of pKa of phenols and kB of PAEs,MPEs and parabens,were written in python.The program embeds molecular descriptors calculated by quantum chemistry and dragon software,which provides a basis for practical application of QSAR models based on three-dimensional molecular structures.In summary,this study employed quantum chemical calculations,experiments,and QSAR modeling to explore prediction methods of PAE and paraben hydrolysis kinetics,which helps to fill data gaps in hydrolysis kinetic parameters of high production volume chemicals such as PAEs and parabens.Furthermore,the current study provides a theoretical foundation and data support for evaluating the environmental persistence of PAEs and parabens.