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A Simple, Robust and Efficient Computational Method for n-Octanol/Water Partition Coefficients of Substituted Aromatic Drugs.

ABSTRACT: In this paper, multiple linear regression (MLR) was used to build quantitative structure property relationship (QSPR) of n-octanol-water partition coefficient (logP_o/w) of 195 substituted aromatic drugs. The molecular descriptors were calculated for each compound by the VLifeMDS. By applying genetic algorithm/multiple linear regressions (GA/MLR) the most relevant descriptors were selected to build a QSPR model. The robustness of the model was characterized by the statistical validation and applicability domain (AD). The prediction results from MLR are in good agreement with the experimental values. The R² and Q²_LOO for MLR are 0.9433, 0.9341. The AD of the model was analyzed based on the Williams plot. The effects of different selected descriptors are described.

SUBMITTER: Bahmani A

PROVIDER: S-EPMC5515958 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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A Simple, Robust and Efficient Computational Method for n-Octanol/Water Partition Coefficients of Substituted Aromatic Drugs.

Bahmani Asrin A Saaidpour Saadi S Rostami Amin A

Scientific reports 20170718 1

In this paper, multiple linear regression (MLR) was used to build quantitative structure property relationship (QSPR) of n-octanol-water partition coefficient (logP<sub>o/w</sub>) of 195 substituted aromatic drugs. The molecular descriptors were calculated for each compound by the VLifeMDS. By applying genetic algorithm/multiple linear regressions (GA/MLR) the most relevant descriptors were selected to build a QSPR model. The robustness of the model was characterized by the statistical validatio ...[more]

PMID: 28720783

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Project description:The partitioning of compounds between aqueous and other phases is important for predicting toxicity. Although thousands of octanol-water partition coefficients have been measured, these represent only a small fraction of the anthropogenic compounds present in the environment. The octanol phase is often taken to be a mimic of the inner parts of phospholipid membranes. However, the core of such membranes is typically more hydrophobic than octanol, and other partition coefficients with other compounds may give complementary information. Although a number of (cheap) empirical methods exist to compute octanol-water (log k OW) and hexadecane-water (log k HW) partition coefficients, it would be interesting to know whether physics-based models can predict these crucial values more accurately. Here, we have computed log k OW and log k HW for 133 compounds from seven different pollutant categories as well as a control group using the solvation model based on electronic density (SMD) protocol based on Hartree-Fock (HF) or density functional theory (DFT) and the COSMO-RS method. For comparison, XlogP3 (log k OW) values were retrieved from the PubChem database, and KowWin log k OW values were determined as well. For 24 of these compounds, log k OW was computed using potential of mean force (PMF) calculations based on classical molecular dynamics simulations. A comparison of the accuracy of the methods shows that COSMO-RS, KowWin, and XlogP3 all have a root-mean-square deviation (rmsd) from the experimental data of ≈0.4 log units, whereas the SMD protocol has an rmsd of 1.0 log units using HF and 0.9 using DFT. PMF calculations yield the poorest accuracy (rmsd = 1.1 log units). Thirty-six out of 133 calculations are for compounds without known log k OW, and for these, we provide what we consider a robust prediction, in the sense that there are few outliers, by averaging over the methods. The results supplied may be instrumental when developing new methods in computational ecotoxicity. The log k HW values are found to be strongly correlated to log k OW for most compounds.

Dataset Information

A Simple, Robust and Efficient Computational Method for n-Octanol/Water Partition Coefficients of Substituted Aromatic Drugs.

Publications

A Simple, Robust and Efficient Computational Method for n-Octanol/Water Partition Coefficients of Substituted Aromatic Drugs.

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