QSPR of n‐Octanol/Water Partition Coefficient of Nonionic Organic Compounds Using Extended Topochemical Atom (ETA) Indices

Abstract

Considering n-octanol/water partition coefficient as an important chemical property in modeling the fate and persistence of chemicals, recently introduced Extended Topochemical Atom (ETA) indices have been used to model n-octanol/water partition coefficient data of 122 nonionic organic compounds which are highly persistent in the environment and reported to bioconcentrate considerably in lipid tissues. In deriving the models, principal component Factor Analysis (FA) followed by Multiple Linear Regression (MLR), stepwise regression, Partial Least Squares (PLS), and Principal Component Regression Analyses (PCRA) were applied as the statistical tools. The model development process was repeated with non-ETA (topological and physicochemical) descriptors and a combination set comprising both the ETA and non-ETA descriptors. The models with ETA indices suggested negative contributions of groups capable of hydrogen bonding and/or polar interactions and positive contributions of volume and degree of halogen substitution to the partition coefficient. Finally, we discuss validation of QSPR models by dividing the dataset into training and test sets based on different strategies, e.g., random division, sorted log K ow data and K-means clusters for the factor scores of the original variable (ETA) matrix without the response property values. The ETA (FA-MLR and stepwise regression) models were also applied on a purely external dataset (n ¼ 35) and acceptable predictive r 2 values (0.582 and 0.651 respectively) were obtained. The results suggest that ETA parameters are sufficiently rich in chemical information to encode the structural features contributing to the n-octanol/water partition coefficient of nonionic organic compounds and thus these merit further assessment to explore their potential in QSAR/QSPR/QSTR modeling.

Prediction of the Fate of Organic Compounds in the Environment From Their Molecular Properties: A Review

“…Therefore, the molecule atoms represent the set of discrete points in space, and the atomic property the function evaluated at those points (Habibi-Yangjeh et al, 2009). Finally, some other miscellaneous geometric descriptors were used: the summation of the steric factors of the additional substituents (E s ; Peijnenburg et al, 1992); the molecular refraction (MR), which affords information about the molecular volume and polarizability (Kim et al, 2007); the excess molar refraction (R 2 ; Abraham, 1993); steric parameters, D and S, that reflect the overall dimension of the molecule (Chaumat et al, 1992); and the sum of the core count for non-hydrogen vertex ( α H ) that may be taken as a measurement of the molecular bulk (Roy et al, 2007).…”

QSTR with Extended Topochemical Atom Indices. 10. Modeling of Toxicity of Organic Chemicals to Humans Using Different Chemometric Tools

“…Among the ETA mod-els, the PLS derived model shows the best predicted variance while among the non-ETA models, the G ⁄ PLS equation gives maximum predicted variance. In case of the combined set of descriptors, the (20) are better than that of the previously published result in the literature (31). Therefore, we have used Eqn (20) for calculating human toxicity of all the 26 compounds ( Table 1).…”

“…In case of the combined set of descriptors, the (20) are better than that of the previously published result in the literature (31). Therefore, we have used Eqn (20) for calculating human toxicity of all the 26 compounds ( Table 1). The intercorrelation matrix for different parameters appearing in the different MLR equations is given in Table 4.…”

“…In this back ground, we have introduced extended topochemical atom (ETA) (10-20) a indices as an extension of the TAU concept in the valence electron mobile (VEM) environment (21-30) b,c and modeled different ecotoxicity data [phenol toxicity to Tetrahymena pyriformis (10), fish toxicity of substituted benzenes (11), nitrobenzene toxicity to Tetrahymena pyriformis (12), acute toxicity of phenylsulfonyl carboxylates to V. fischeri (13,14), acute toxicity of benzene derivatives to tadpoles (Rana japonica) (15), toxicity of substituted benzenes to Saccharomyces cerevisiae (16), inhibition of substituted phenols on germination rate of Cucumis sativus (17), toxicity of diverse compounds to Chlorella vulgaris (18)] and property data [bioconcentration factors (19) and n-octanol-water partition coefficient (20) of nonionic organic compounds] to establish the utility of ETA indices using different chemometric tools. In our present work, we have focused to model the toxicity of 26 organic compounds including some pharmaceuticals to humans (31) ( Table 1) using ETA descriptors and tried to prove the informative nature of the ETA descriptors.…”

QSTR with extended topochemical atom (ETA) indices. 14. QSAR modeling of toxicity of aromatic aldehydes to Tetrahymena pyriformis

“…The ETA [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] indices formulated based on modification of TAU descriptors [38][39][40][41][42][43][44][45][46][47][48][49][50], which were developed in the valence electron mobile (VEM) environment, have been used to develop the QSTR models for 40-h T. pyriformis toxicity of 77 aromatic aldehydes. Some basic parameters of the ETA scheme used in the development of QSTR models for the above mentioned dataset have been defined in Supplementary Materials section.…”