Predicting solvent-water partitioning of charged organic species using quantum-chemically estimated Abraham pp-LFER solute parameters

Abstract

Methods for obtaining accurate predictions of solvent-water partitioning for neutral organic chemicals (e.g., Kow) are well-established. However, methods that provide comparable accuracy are not available for predicting the solvent-water partitioning of ionic species. Previous methods for addressing charge contributions to solvent-water partitioning rely on charged solute descriptors which are obtained from regressions to neutral species descriptors as well as charged descriptors which are specific to unique charge-functionalities and structural moieties. This paper presents a method for obtaining Abraham poly-parameter linear free energy relationship (pp-LFER) descriptors using quantum chemical calculations and molecular structure, only. The method utilizes a large number of solvent-water systems to overcome large errors in individual quantum chemical computations of ionic solvent-water partition coefficients. The result is a single set of quantum-chemically estimated Abraham solute parameters (QCAP) which are solvent-independent, and can be used to predict the solvent-water partitioning of ionic species.Predictions of solvent-water partition coefficients for ionic species using quantum-chemically estimated Abraham parameters (QCAPs) are shown to provide improved accuracy compared over both existing Absolv-estimated Abraham solute parameters (AAP) as well as direct a priori quantum chemical (QC) calculations for partitioning of anionic solutes in 4 organic solvent-water systems (RMS = 0.740, 2.48 and 0.426 for the Absolv, QC and QCAP methods, respectively). For quaternary amine cations in the octanol-water system the RMS errors of the solvent-water partition coefficients were larger and similar between the two Abraham models (RMSE = 0.997 and 1.16, for the AAP and QCAP methods, respectively). Both methods showed significant improvement over direct QC calculations (RMSE = 2.82).