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

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
(Kislip/w and Kislip/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 Kislip/w at the physiological temperature
of 37 °C. However, to date, a comprehensive collection and sufficiently
reliable PP-LFERs for Kislip/w and Kislip/a at the
most common standard temperature of 25 °C are still lacking.
In this study, experimentally based Kislip/w and/or Kislip/a values at 25 °C for 278 compounds were extensively
collected or converted from the literature. Subsequently, PP-LFERs
were calibrated for Kislip/w and Kislip/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 Kislip/w or Kislip/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.