Prediction of Physicochemical Properties of Organic Compounds from 2D Molecular Structure – Fragment Methods vs. LFER Models

Abstract

A large number of models is available to predict physicochemical properties directly from the two-dimensional molecular structure. An alternative to conventional fragment methods is given by linear free-energy relationships (LFERs) employing Abraham parameters. The latter have a solid mechanistic background, but a drawback in practice is the limited availability of Abraham parameters for substances of interest. As a consequence, more complex compounds typically require the estimation of Abraham parameters from the chemical structure. Comparative analysis of prediction methods for Henry's law constant and sorption to soil organic matter shows that at present, fragment methods are superior to the LFER approach when employing calculated Abraham parameters. For the subset of typically more simple compounds with experimental Abraham parameters, the respective LFERs are competitive to general-purpose fragment models. The discussion includes analyses of compound subsets without and with hydrogen bond functionalities, and of the impact of structural complexity on the model performance.