Developing the QSPR model for predicting the storage lipid/water distribution coefficient of organic compounds

Highlights

• A predictive model for storage lipid/water distribution coefficient was developed.

• The model yields outstanding fitting performance, robustness, and predictive ability.

• Hydrophobic and electrostatic interactions and molecular size dominate log K_lip/w.

• The model can be used in a wide application domain to predict log K_lip/w values.

Abstract

The distribution of organic compounds in stored lipids affects their migration, transformation, bioaccumulation, and toxicity in organisms. The storage lipid/water distribution coefficient (log K_lip/w) of organic chemicals, which quantitatively determines such distribution, has become a key parameter to assist their ecological security and health risk. Due to the impossibility to measure K_lip/w values for a huge amount of chemicals, it is necessary to develop predictive approaches. In this work, a quantitative structure-property relationship (QSPR) model for estimating log K_lip/w values of small organic compounds was constructed based on 305 experimental log K_lip/w values. Quantum chemical descriptors and n-octanol/water partitioning coefficient were employed to characterize the intermolecular interactions that dominate log K_lip/w values. The hydrophobic and electrostatic interactions and molecular size have been found to play important roles in governing the distribution of chemicals between lipids and aqueous phases. The regression (R² = 0.959) and validation (Q² = 0.960) results indicate good fitting performance and robustness of the developed model. A comparison with the predictive performance of other commercial software further proves the higher accuracy and stronger predictive ability of the developed K_lip/w predictive model. Thus, it can be used to predict the K_lip/w values of cycloalkanes, long-chain alkanes, halides (with fluorine, chlorine, and bromine as substituents), esters (without phosphate groups), alcohols (without methoxy groups), and aromatic compounds.

Key words： Storage lipid/water distribution coefficient; log K_lip/w; Organic compounds; QSPR; Quantum chemical descriptors

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Nos. 21707122 and 21677133) and National College Students Innovation and Entrepreneurship Training Program (No. 202010345069), which is gratefully acknowledged.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11783-020-1316-z and is accessible for authorized users.

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