Prediction of the n-octanol/water partition coefficients in the SAMPL6 blind challenge from MST continuum solvation calculations

The IEFPCM/MST continuum solvation model is used for the blind prediction of n -octanol/water partition of a set of 11 fragment-like small molecules within the SAMPL6 Part II Partition Coefficient Challenge. The partition coefficient of the neutral species (log P ) was determined using an extended p...

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Bibliographic Details
Published in:	Journal of computer-aided molecular design Vol. 34; no. 4; pp. 443 - 451
Main Authors:	Zamora, William J., Pinheiro, Silvana, German, Kilian, Ràfols, Clara, Curutchet, Carles, Luque, F. Javier
Format:	Journal Article
Language:	English
Published:	Cham Springer International Publishing 01-04-2020 Springer Nature B.V
Subjects:	Animal Anatomy Chemistry Chemistry and Materials Science Coefficients Computer Applications in Chemistry Heterocyclic compounds Histology Mathematical models Morphology Parameterization Physical Chemistry Root-mean-square errors Solvation Solvation free energy SAMPL6 Partition coefficients Continuum solvation models MST model
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Summary:	The IEFPCM/MST continuum solvation model is used for the blind prediction of n -octanol/water partition of a set of 11 fragment-like small molecules within the SAMPL6 Part II Partition Coefficient Challenge. The partition coefficient of the neutral species (log P ) was determined using an extended parametrization of the B3LYP/6-31G(d) version of the Miertus–Scrocco–Tomasi continuum solvation model in n -octanol. Comparison with the experimental data provided for partition coefficients yielded a root-mean square error (rmse) of 0.78 (log P units), which agrees with the accuracy reported for our method (rmse = 0.80) for nitrogen-containing heterocyclic compounds. Out of the 91 sets of log P values submitted by the participants, our submission is within those with an rmse < 1 and among the four best ranked physical methods. The largest errors involve three compounds: two with the largest positive deviations (SM13 and SM08), and one with the largest negative deviations (SM15). Here we report the potentiometric determination of the log P for SM13, leading to a value of 3.62 ± 0.02, which is in better agreement with most empirical predictions than the experimental value reported in SAMPL6. In addition, further inclusion of several conformations for SM08 significantly improved our results. Inclusion of these refinements led to an overall error of 0.51 (log P units), which supports the reliability of the IEFPCM/MST model for predicting the partitioning of neutral compounds.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0920-654X 1573-4951
DOI:	10.1007/s10822-019-00262-4