Polyparameter Linear Free Energy Relationships for Partitioning of Neutral Organic Compounds to Storage Lipids

Abstract

Storage lipids are an important compartment in the bioaccumulation of neutral organic compounds. Reliable models for predicting storage lipid−water and storage lipid−air partition coefficients (K islip/w and K islip/a ), as well as their temperature dependence, are considered useful. Polyparameter linear free energy relationships (PP-LFERs) are accurate, general, and mechanistically clear models for predicting partitioning-related physicochemical quantities. About a decade ago, PP-LFERs were calibrated for K islip/w at the physiological temperature of 37 °C. However, to date, a comprehensive collection and sufficiently reliable PP-LFERs for K islip/w and K islip/a at the most common standard temperature of 25 °C are still lacking. In this study, experimentally based K islip/w and/or K islip/a values at 25 °C for 278 compounds were extensively collected or converted from the literature. Subsequently, PP-LFERs were calibrated for K islip/w and K islip/a at 25 °C, performing well over 10 orders of magnitude with root-mean-square errors of 0.17−0.21 log units for compounds with reliable descriptors. Furthermore, standard internal energy changes of transfer from water or air to storage lipids for 158 compounds were derived and used to calibrate PP-LFERs for estimating the temperature dependence of K islip/w or K islip/a . Additionally, using PP-LFERs, low-density polyethylene was confirmed to be a better storage lipid analogue than silicone and polyoxymethylene in the equilibrium passive sampling of nonpolar and H-bond acceptor polar compounds.