Octanol/Air Partition Coefficient—A General-Purpose Fragment Model to Predict Log Koa from Molecular Structure

摘要

The octanol/air partition coefficient Koi is important for assessing the bioconcentration of airborne xenobiotics in foliage and in air-breathing organisms. Moreover, Koa informs about compound partitioning to aerosols and indoor dust, and complements the octanol/water partition coefficient Kow and the air/water partition coefficient Ka” for multimedia fate modeling. Experimental log Koa at 25 °C has been collected from literature for 2161 compounds with molecular weights from 16 to 959 Da. The curated data set covers 18.2 log units (from —1.0 to 17.2). A newly developed fragment model for predicting log Koa from molecular structure outperforms COSMOtherm, EPI-Suite KOAWIN, OPERA, and linear solvation energy relationships (LSERs) regarding the root-mean-squared error (rms) and the maximum negative and positive errors (mne and mpe) (rms: 0.57 vs 0.86 vs 1.09 vs 1.19 vs 1.05—1.53, mne: —2.55 vs —3.95 vs —7.51 vs —7.54 vs (—5.63) — (—7.34), mpe: 2.91 vs 5.97 vs 7.54 vs 4.24 vs 6.89—10.2 log units). The prediction capability, statistical robustness, and sound mechanistic basis are demonstrated through initial separation into a training and prediction set (80:20%), mutual leave-50%-out validation, and target value scrambling in terms of temporarily wrong compound-i ., allocations. The new general-purpose model is implemented in a fully automatized form in the ChemProp software available to the public. Regarding Koà indirectly determined through Kow and i