Department of Nutrition, Food Science and Gastronomy, Faculty of Pharmacy and Food Sciences, Institute of Biomedicine (IBUB), Institute of Theoretical and Computational Chemistry (IQTCUB) and Campus Torribera, University of Barcelona, 08921, Santa Coloma De Gramenet, Spain.
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry and Institute of Theoretical and Computational Chemistry (IQTCUB), Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII 27-31, 08028, Barcelona, Spain.
J Comput Aided Mol Des. 2020 Apr;34(4):443-451. doi: 10.1007/s10822-019-00262-4. Epub 2019 Nov 27.
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.
IEFPCM/MST 连续溶剂化模型用于对 SAMPL6 第二部分分配系数挑战赛中一组 11 种类似片段小分子的正辛醇/水分配系数进行盲预测。中性物种的分配系数（log P）是使用扩展的 B3LYP/6-31G(d)版本的 Miertus-Scrocco-Tomasi 连续溶剂化模型在正辛醇中确定的。与提供的实验分配系数数据进行比较，得出均方根误差（rmse）为 0.78（log P 单位），这与我们方法（rmse=0.80）报告的含氮杂环化合物的精度一致。在参与者提交的 91 组 log P 值中，我们的提交值在 rmse<1 的值内，并且在四个排名最高的物理方法中。最大的误差涉及三种化合物：两种具有最大正偏差（SM13 和 SM08），一种具有最大负偏差（SM15）。这里我们报告了 SM13 的 log P 的电位测定，得到的值为 3.62±0.02，与大多数经验预测相比，与 SAMPL6 中报告的实验值更一致。此外，进一步包含 SM08 的几个构象显著提高了我们的结果。包含这些改进使总体误差为 0.51（log P 单位），这支持 IEFPCM/MST 模型预测中性化合物分配的可靠性。
