Predicting the Temperature Dependence of the Octanol–Air Partition Ratio: A New Model for Estimating ΔU^∘_OA

The octanol–air partition ratio ( K OA ) describes the partitioning of a chemical between air and octanol and is often used to approximate other partitioning phenomena in environmental chemistry (e.g., blood–air, atmospheric particulate matter–air, polyurethane foam-air). Such partitioning processes often occur at environmental temperatures other than 25 °C. Enthalpies ΔH^∘_OA or internal energies ΔU^∘_OA of phase transfer are used to express the temperature dependence of the K OA . Existing poly-parameter linear free energy relationships (ppLFERs) for predicting ΔH^∘_OA were developed using a relatively small dataset. In this work we utilize a recently developed comprehensive K OA database to create and curate a ΔU^∘_OA dataset containing 195 chemicals and use this dataset in the development of new predictive equations. Using the QSAR development platform QSARINS we evaluate the use of Abraham descriptors, other molecular descriptors, and the log 10 K OA at 25 °C as variables in different multilinear regression equations for ΔU^∘_OA . The ΔU^∘_OA of neutral organic chemicals can be reliably predicted using only the log 10 K OA (RMSE EXT = 6.86 kJ·mol −1 , R^2 _adj = 0.94), only the solute’s hydrogen acidity A and the logarithm of the hexadecane–air partition ratio L (RMSE EXT = 7.23 kJ·mol −1 , R^2 _adj = 0.93), or A and log 10 K OA (RMSE EXT = 6.76 kJ·mol −1 , R^2 _adj = 0.95).