Expanding the applicability domain of QSPRs for predicting water solubility and vapor pressure of PFAS

Abstract

This work aimed to verify whether it is possible to extend the applicability domain (AD) of existing QSPR (Quantitative Structure-Property Relationship) models by employing a strategy involving additional quantum-chemical calculations. We selected two published QSPR models: for water solubility, logS_W, and vapor pressure, logVP of PFAS as case studies. We aimed to enlarge set of compounds used to build the model by applying factorial planning to plan the augmentation of the set of these compounds based on their structural features (descriptors). Next, we used the COSMO-RS model to calculate the logS_W and logVP for selected chemicals. This allowed filling gaps in the experimental data for further training QSPR models. We improved the published models by significantly extending number of compounds for which theoretical predictions are reliable (i.e., extending the AD). Additionally, we performed external validation that had not been carried out in original models. To test effectiveness of the AD extension, we screened 4519 PFAS from NORMAN Database. The number of compounds outside the domain was reduced comparing the original model for both properties. Our work shows that combining physics-based methods with data-driven models can significantly improve the performance of predictions of phys-chem properties relevant for the chemical risk assessment.

Keywords: Applicability domain (AD); COSMO-RS; PFAS; QSPR; Vapor pressure; Water solubility.