Theoretical Linear Solvation Energy Relationship Research Articles

Development of predictive models for silicone rubber-water partition coefficients of hydrophobic organic contaminants.

The silicone rubber passive sampling technique is extensively applied to monitor the aqueous freely dissolved concentration of hydrophobic organic compounds (HOCs). The silicone rubber-water partition coefficient (Ksrw) is an important parameter to accurately measure the concentrations of chemicals using passive sampling devices. In this study, two theoretical linear solvation energy relationship (TLSER) models and a quantitative structure-property relationship (QSPR) model were developed for predicting the Ksrw of HOCs. The 119 model compounds studied here included 31 personal care products, such as musks, UV-filters, and organophosphate flame retardants, as well as "conventional" pollutants, such as polycyclic aromatic hydrocarbons and polychlorinated biphenyls. The statistical parameters indicated that the final QSPR model with seven descriptors for all 119 chemicals had a satisfactory goodness-of-fit (Radj2 = 0.898), robustness (QLOO2 = 0.881) and predictive ability (Qext-F1,2,32 = 0.897-0.926). In comparison, the results of one TLSER model with four descriptors for 113 chemicals (Radj2 = 0.826, QLOO2 = 0.790, Qext-F1,2,32 = 0.805-0.837) and another TLSER model with one descriptor for 5 chemicals (Radj2 = 0.747, QLOO2 = 0.647) were also acceptable. The applicability domains of the obtained models covered chemicals containing hydroxyl, imino groups, carbonyl groups, ether bonds, halogen atoms, sulfur atoms, phosphorus atoms, nitro groups, and cyano groups. In addition, the structural features governing the partition behavior of chemicals between silicone rubber and water were explored through interpretation of appropriate mechanisms.

Predicting low density polyethylene-air partition coefficients using theoretical linear solvation energy relationships

Predicting low density polyethylene-air partition coefficients using theoretical linear solvation energy relationships

Development and evaluation of MTLSER and QSAR models for predicting polyethylene-water partition coefficients

Current study was aimed to make further improvements in measuring low density polyethylene (LDPE) -water partition coefficient (KPE-w) for organic chemicals. Modified theoretical linear solvation energy relationship (MTLSER) model and quantitative structure activity relationship (QSAR) model were developed for predicting KPE-w values from chemical descriptors. With the MTLSER model, α (average molecular polarizability), μ (dipole moment) and q- (net charge of the most negative atoms) as significant variables were screened. With the QSAR model, main control factors of KPE-w values, such as CrippenLogP (Crippen octanol-water partition coefficient), CIC0 (neighborhood symmetry of 0-order) and GATS2p (Geary autocorrelation-lag2/weighted by polarizabilities) were studied. As per our best knowledge, this is the first attempt to predict polymer-water partition coefficient using the MTLSER model. Statistical parameters, correlation coefficient (R2) and cross-validation coefficients (Q2) were ranging from 0.811 to 0.951 and 0.761 to 0.949, respectively, which indicated that the models appropriately fit the results, and also showed robustness and predictive capacity. Mechanism interpretation suggested that the main factors governing the partition process between LDPE and water were the molecular polarizability and hydrophobicity. The results of this study provide an excellent tool for predicting log KPE-w values of most common hydrophobic organic compounds, within the applicability domains to reduce experimental cost and time for innovation.

Exploring adsorption of neutral aromatic pollutants onto graphene nanomaterialsviamolecular dynamics simulations and theoretical linear solvation energy relationships

TLSER models were developed for the first time to predict the adsorption equilibrium coefficients onto graphene and graphene oxide nanosheets.

Development of TLSER model and QSAR model for predicting partition coefficients of hydrophobic organic chemicals between low density polyethylene film and water

Partition coefficients are vital parameters for measuring accurately the chemicals concentrations by passive sampling devices. Given the wide use of low density polyethylene (LDPE) film in passive sampling, we developed a theoretical linear solvation energy relationship (TLSER) model and a quantitative structure-activity relationship (QSAR) model for the prediction of the partition coefficient of chemicals between LDPE and water (Kpew). For chemicals with the octanol–water partition coefficient (log Kow) <8, a TLSER model with Vx (McGowan volume) and qA− (the most negative charge on O, N, S, X atoms) as descriptors was developed, but the model had relatively low determination coefficient (R2) and cross-validated coefficient (Q2). In order to further explore the theoretical mechanisms involved in the partition process, a QSAR model with four descriptors (MLOGP (Moriguchi octanol-water partition coeff.), P_VSA_s_3 (P_VSA-like on I-state, bin 3), Hy (hydrophilic factor) and NssO (number of atoms of type ssO)) was established, and statistical analysis indicated that the model had satisfactory goodness-of-fit, robustness and predictive ability. For chemicals with log KOW>8, a TLSER model with Vx and a QSAR model with MLOGP as descriptor were developed. This is the first paper to explore the models for highly hydrophobic chemicals. The applicability domain of the models, characterized by the Euclidean distance-based method and Williams plot, covered a large number of structurally diverse chemicals, which included nearly all the common hydrophobic organic compounds. Additionally, through mechanism interpretation, we explored the structural features those governing the partition behavior of chemicals between LDPE and water.

Development and validation of theoretical linear solvation energy relationship models for toxicity prediction to fathead minnow (pimephales promelas)

The acute toxicity predictive models are vitally important for the toxicological information used in the ecological risk assessments. In this study, we used Verhaar classification scheme to group compounds into five modes of toxic action. The quantum chemical descriptors that characterize the electron donor–acceptor property of the compounds were introduced into the theoretical linear solvation energy relationship (TLSER) models. The predictive models have relatively larger data sets, which imply that they cover a wide applicability domain (AD). All models were developed following the Organization for Economic Co-operation and Development (OECD) QSAR models development and validation guidelines. The adjusted determination coefficient (Radj2) and external explained variance (QEXT2) of the models were ranging from 0.707 to 0.903 and 0.660 to 0.858, respectively, indicating high goodness-of-fit, robustness and predictive capacity. The cavity term (McGowans volume) was the most significant descriptor in the models. Moreover, the electron donor–acceptor (E-TLSER) models are comparable to the TLSER models for the toxicity prediction to fathead minnow. Thus, the E-TLSER models developed can be used to predict acute toxicity of new compounds within the AD.

Theoretical prediction for the infinite dilution activity coefficients of organic compounds in ionic liquids

On the basis of the theoretical linear solvation energy relationship (TLSER) suggested by Wilson et al. and the quantum chemical descriptors computed by AM1 Hamiltonian, a predicting model was developed to characterize the activity coefficients at infinite dilution γi∞ of 34 organic solutes in ionic liquids (ILs) 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM][CF3SO3]) and 1-propyl-2,3-dimethylimidazolium tetrafluoroborate ([PDMIM][BF4]) at 323.15 K. The results showed that the model had an good correlation and could successfully describe γi∞. In addition, correlation parameters are analyzed to understand the interactions that affect infinite dilution activity coefficients.

Prediction of supercooled liquid vapor pressures and n-octanol/air partition coefficients for polybrominated diphenyl ethers by means of molecular descriptors from DFT method

The molecular geometries of 209 polybrominated diphenyl ethers (PBDEs) were optimized at the B3LYP/6-31G⁎ level with Gaussian 98 program. The calculated structural parameters were taken as theoretical descriptors to establish two novel QSPR models for predicting supercooled liquid vapor pressures ( P L) and octanol/air partition coefficients ( K OA) of PBDEs based on the theoretical linear solvation energy relationship (TLSER) model, respectively. The two models achieved in this work both contain three variables: most negative atomic partial charge in molecule ( q - ), dipole moment of the molecules ( μ) and mean molecular polarizability ( α), of which R 2 values are both as high as 0.997, their root-mean-square errors in modeling (RSMEE) are 0.069 and 0.062 respectively. In addition, the F-value of two models are both evidently larger than critical values F 0.05 and the variation inflation factors (VIF) of variables herein are all less than 5.0, suggesting obvious statistic significance of the P L and K OA predicting models. The results of Leave-One-Out (LOO) cross-validation for training set and validation with external test set both show that the two models obtained exhibited optimum stability and good predictive power. We suggest that the QSPRs derived here can be used to predict accurately P L and K OA for non-tested PBDE congeners from Mono-BDEs to Hepta-BDEs and from Mono-BDEs to Hexa-BDEs, respectively.

Study of Quantitative Structure–Retention Relationship (QSRR) of Gas Chromatography for Polychlorinated Dibenzothiophenes on Non‐polar Columns

AbstractOptimized calculation of 135 Polychlorinated Dibenzothiophenes (PCDTs) was carried out at B3LYP/6‐31G* level with Gaussian 98 program. The structural and thermodynamic parameters identified with the Theoretical Linear Solvation Energy Relationship (TLSER) model were employed as theoretical descriptors in the Quantitative Structure–Retention Relationship (QSRR) models derived to predict Retention Indices (RI) of PCDTs. Two QSRR models developed for RI of PCDTs contain only one variable: the mean molecular polarizability (α) and entropy (S⊖), respectively. The best fitted equation for the correlation between RI and α of 25 PCDTs with experimental data was RI=−126.52(±2.86)+0.97(±0.01)α with R2 as 0.9942, SD as 2.22, suggesting high accuracy of the RI predicting model. The correlation between RI and S⊖ is strong, and the equation was RI=−184.17 (±3.09)+0.48(±0.01)S⊖ with R2 as 0.9961, SD as 1.81. Furthermore, using position of Cl substitution (NPCS) method, QSRR model of PCDTs was obtained: RI=6.23(±0.75)+13.36(±0.19)N with R2 as 0.9953, SD as 1.99. Method validation also showed that the three models of this study exhibit optimum stability. Finally, RI values of 110 PCDT congeners without experimental value were also predicted with the three models, respectively.

QSPR Study on the Aqueous Solubility (−lgSw) and n‐Octanol/Water Partition Coefficients (lgKow) of Polychlorinated Dibenzo‐p‐dioxins (PCDDs)

AbstractOptimized calculation of 75 Polychlorinated Dibenzo‐p‐dioxins (PCDDs) and their parent compound DD was carried out at B3LYP/6‐31G* level with GAUSSIAN 98 program. The structural parameters identified with the Theoretical Linear Solvation Energy Relationship (TLSER) model were employed as theoretical descriptors in the Quantitative Structure–Property Relationship (QSPR) models derived to predict the aqueous solubility (−lgSw) and n‐octanol/water partition coefficients (lgKow) of PCDDs. The regression model obtained to predict −lgSw contains only one variable: the mean molecular polarizability (α). The best fitted equation for the correlation between −lgSw and α of 12 PCDDs was −lgSw=−3.6425+0.0693α with r2 as 0.9776, Standard Deviation (SD) as 0.30, and suggesting high accuracy of the −lgSw predicting model. At the same time, there exists high correlation (r2=0.8862) between n‐octanol/water partition coefficients (lgKow) and the mean molecular polarizability (α), and the SD is small. The mean molecular polarizability (α) is the only theoretical descriptor used in the QSPR model derived to predict lgKow.

Determination of Mineral and Trace Elements in Ganoderma Lucidum Consumed in China, Vietnam and Korea

The theoretical linear solvation energy relationship(TLSER) approach was adopted to predict the aqueous solubility and n-octanol/water partition coefficient of three groups of environmentally important chemicals-polychlorinated biphenyls(PCBs), polychlorinated dibenzodioxins and dibenzofurans (PCDDs and PCDFs). For each compound, five quantum parameters were calculated using AM1 semiempirical molecular orbital methods and used as structure descriptors: average molecular polarizability(alpha), energy of the lowest unoccupied molecular orbit( E(LUMO)), energy of the highest occupied molecular orbit( E(HOMO)), the most positive charge on a hydrogen atom (q+), and the most negative atomic partial charge(q-) in the solute molecule. Then standard independent variables in TLSER equation was extracted and two series of quantitative equations between these quantum parameters and aqueous solubility and n-octanol/water partition coefficient were obtained by stepwise multiple linear regression(MLR) method. The developed equations have both quite high accuracy and explicit meanings. And the cross-validation test illustrated the good predictive power and stability of the established models. The results showed that TLSER could be used as a promising approach in the estimation of partition and solubility properties of macromolecular chemicals, such as persistent organic pollutants.

Quantitative structure–property relationships for predicting subcooled liquid vapor pressure ( PL) of 209 polychlorinated diphenyl ethers (PCDEs) by DFT and the position of Cl substitution (PCS) methods

Optimization of the molecular geometry of 209 polychlorinated diphenyl ethers (PCDEs) and diphenyl ether (DE) were carried out at the B3LYP/6-31G* level with Gaussian 98 program. Based on the theoretical linear solvation energy relationship (TLSER) model, the obtained structural parameters were taken as theoretical descriptors to establish the first novel QSPR model (I) for predicting subcooled liquid vapor pressure ( P L) of PCDEs. The model (I) achieved in this work contains three variables: most negative atomic partial charge in molecule ( q − ), dipole moment of the molecules ( μ) and mean molecular polarizability ( α), of which r 2=0.988, SD=0.134. Meanwhile, it was found that there was significant correlation between the Cl substitution positions and some structural parameters. Consequently, the numbers of Cl substitution positions were also taken as theoretical descriptors to establish the second novel QSPR model (II) for predicting P L of all PCDE congeners, of which r 2=0.991, SD=0.112. In addition, the t-values of two models are both large and the variation inflation factors (VIF) of variables herein are all less than 5.0, suggesting significant statistics of the P L predicting models. And the results of cross-validation test also showed that the second model exhibited optimum stability and better predictive power. Moreover, results of prediction were further compared with data from similar studies by semi-empirical PM3 method, molecular connectivity indices (MCIs) method and molecular descriptors method.

Calculation of Solubility of Organic Compounds in Supercritical CO2 based on Quantitative Structure-Activity Relationships

Calculation of solubility of organic compounds in supercritical CO2 based on the quantitative structure-activity relationships (QSAR) and theoretical linear solvation energy relationships (TLSER) have an advantage of its ability of extrapolation over the empirical correlation, since the TLSER correlations use computationally derivable sets of molecular parameters. In this study, solubilities of 32 organic compounds in supercritical CO2 at 308 K, 20 MP were correlated based on the TLSER method using four molecular properties of solute; polarizability index, molecular orbital acidity, electrostatic basicity and electrostatic acidity. Molecular properties of solute were determined with PM3 method and COSMO-PM3 method. While a fairly reasonable correlation was found for many compounds, relatively large deviation was found for some compounds.

Estimation of the aqueous solubility (−lg Sw) of all polychlorinated dibenzo-furans (PCDF) and polychlorinated dibenzo- p-dioxins (PCDD) congeners by density functional theory

Optimized calculations of 76 polychlorinated dibenzo- p-dioxins and 136 polychlorinated dibenzo-furans were carried out at the B3LYP/6-31G* level in gaussian 98 program. Based on the theoretical linear solvation energy relationship (TLSER) model, the obtained structural parameters were taken as theoretical descriptors to establish a novel QSPR model for predicting aqueous solubility (−lg S w) of polychlorinated dibenzo- p-dioxins and polychlorinated dibenzo-furans. The new model of −lg S w achieved in this work contains two variables, dipole moment of the molecules ( μ) and the polarizability ( α), of which R 2=0.9403, SD=0.40. And the results of cross-validation test ( q 2=0.9153) and method validation also showed that the model of this study exhibited optimum stability and better predictive power than semi-empirical method.

Estimation of n-octanol/water partition coefficients ( Kow) of all PCB congeners by density functional theory

Optimized calculation of 209 PCBs was carried out at B3LYP/6-31G* level in gaussian98 program. Based on the theoretical linear solvation energy relationship (TLSER) model, the obtained structural parameters were taken as theoretical descriptors to establish the novel QSPR model for predicting n-octanol/water partition coefficients (lg K ow) of PCBs. The new model achieved in this work contains three variables, polarizability α, E LUMO and E HOMO, of which r 2=0.9484, SD=0.18, with larger t values. In addition, the variation inflation factors (VIF) of variables in the present model are all less than 5.0, suggesting high accuracy of the lg K ow predicting model. And the results of cross-validation test ( q 2=0.9455) and method validation also showed the model of this study exhibited optimum stability and better predictive power than semiempirical method.

QSPR modeling of adsorption coefficient Koc of alkyl(1-phenylsulfonyl) cycloalkane-carboxylates on soil and sediments using MLSER model and ab initio

Based on the modified theoretical linear solvation energy relationship (MTLSER) model and quantum chemical descriptors computed at HF/STO-3G, HF/LANL2DZ, B3LYP/LANL2D and B3LYP/6-31G* levels, respectively, different quantitative structure–property relationship (QSPR) models of adsorption coefficient ( K oc) on soil and sediments of 28 alkyl(1-phenylsulfonyl) cycloalkane-carboxylates were developed. It is suggested that all the eight models developed in the present study have good correlation and relatively small error, in which the model with three variables, i.e. the lowest unoccupied molecular orbital ( E LUMO), the most negative formal charge ( q −) and molecular polarizability ( α) as descriptors obtained from B3LYP/LANL2DZ level, exhibited the best optimum correlation ( r 2=0.9650, q 2=0.9446), larger t values and the smallest error. It was also found that molecular polarizability is the most significant factor influencing log K oc, and the value of log K oc increases with increasing E LUMO, q − and α. The result showed that MTLSER models achieved from ab initio calculation are better than that from semi-empirical AM1 method.

Approach to predict partitioning of organic compounds from air into airborne particulate

Based on the theoretical linear solvation energy relationship and quantum chemical descriptors computed by AM1 Hamiltonian, a new approach was developed to predict the partitioning of some organic compounds between the airborne particulate and air. It could be successfully used to study the partitioning of organic compounds from air into airborne particulate, and evaluate the potential risk of organic compounds.

Comparison of an empirical and a theoretical linear solvation energy relationship applied to the characterization of solute distribution in a poly(ethylene) glycol-salt aqueous biphasic system.

A Linear Solvation Energy Relationship (LSER) developed by Abraham has been applied to the partition of organic solutes in an Aqueous Biphasic System (ABS) and to published values of their 1-octanol/water partition coefficients. The results are compared to the application of a conceptually similar Theoretical Linear Solvation Energy Relationship (TLSER) developed by Famini and co-workers. Differences and similarities in the molecular properties highlighted by each LSER are discussed. The theoretical relationship of Famini, although modeled on the approach of Abraham, seems not to encapsulate molecular properties in the same way as the Abraham's empirical relationship. However, this theoretical approach has the great merit of computational simplicity, and it is concluded that efforts directed toward its improvement could be rewarding.

Prediction of percutaneous drug permeability using modified theoretical linear solvation energy relationship

To predict the percutaneous drug permeability coefficients with modified regression equation. The semiempirical self-consistent field molecular orbital calculation AM1 method was used to calculate the quantum chemical parameters and the modified theoretical linear solvation energy relationship was used to obtain the regression equation of the permeability coefficients of drugs through human epidermis. The permeability coefficients (P) of 36 nonelectrolytes were well linearly correlated with their theoretical descriptors including molecular volume (V), hydrogen bond acidity (sum alpha(2)(H)), hydrogen bond basicity (sum beta(2)(H)) and polarizability index (pi(1)). The regression equation was logP=-6.790+1.571 V+0.1550 pi(1)-1.295 sum alpha(2)(H)-2.485 sum beta(2)(H)(n=36,r=0.9777). The modified theoretical linear solvation energy relationship can be used to predict the skin permeability of drugs.

Linear Free Energy Relationship Analysis of Solvent Effects on Singlet Oxygen Reactions

Linear solvation energy relationship, LSER, and theoretical linear solvation energy relationship, TLSER, formalisms are applied to the analysis of solvent effects on singlet oxygen reactions. Treatments allow quantitative evaluation of solvent effects and are powerful tools for interpreting the mechanism of the process. Both formalisms are applied to several amino derivatives, where for all types of solvents there is a single pattern, implying a common reaction mechanism involving charge transfer intermediates. The relative contribution of the different descriptors depends upon the compound considered, but a common feature is a significant negative dependence on the α parameter, which measures solvent acidity. Correlation equations obtained from analysis of singlet oxygen reactions with 1,3-dienes also exhibit a common dependence on the ρH parameter, that accounts for the cohesive energy of the solvent, and reflects the negative activation volume associated with concerted or partially concerted reactions. These formalisms can be also used to determine the main reaction center in polyfunctional compounds (e.g. boldine, vincamine, reserpine, and furosemide), to detect changes in the reaction mechanism with solvent properties (furosemide), and to evaluate the relative contribution of tautomers in equilibrium to the total reaction rate (piroxicam). This treatment could be used to analyze singlet oxygen reactivity in microheterogeneous systems and to predict relative rate constants in these systems.