Improved method for estimating water solubility from octanol water partition coefficient
Improved method for estimating water solubility from octanol water partition coefficient
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DOI：
10.1002/etc.5620150205
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发表时间：
1996-02-01
影响因子：
4.1
通讯作者：
Boethling, RS
中科院分区：
文献类型：
--
作者：
Meylan, WM;Howard, PH;Boethling, RS
水溶解度是化学品风险评估中的一个关键属性，但通常无法获得测量值。估算不同和复杂结构的溶解度的最实用方法涉及对辛醇/水分配系数（log K-ow）的对数进行回归。然而，目前使用的方程是从相对较小的训练集（200-300个化合物）开发的。我们的目标是通过检查一个更大的和多样化的训练集，以升级日志K-ow为基础的方法，如果可能的话，以提高估计精度进一步通过纳入一系列简单的校正因子。我们还评估了熔融温度（Tm）和分子量（MW）的贡献。可获得训练组（n = 1，450）中所有化合物的水溶性、log K-ow和T-m（仅固体）的测量值。该数据集的最佳方程包括log K-ow，T-m，MW和12个校正因子作为自变量，r（2）= 0.970，SD = 0.409，ME = 0.313。817种化合物的独立验证集的统计与这些结果一致：r（2）= 0.902，SD = 0.615，ME = 0.480。我们发现，T-m有助于显着固体的估计精度;此外，MW也增加了准确性; log K-ow的测量值，和T-m产生更准确的溶解度估计比估计值;和新的方法优于其他广泛使用的通用方程的基础上log K-ow。
Water solubility is a critical property in risk assessments for chemicals, but measured values are often unavailable. The most practical approach to estimating solubility for diverse and complex structures involves regression against the logarithm of the octanol/water partition coefficient (log K-ow). However, currently used equations were developed from relatively small training sets (200-300 compounds). Our objective was to upgrade log K-ow-based methods by examining a much larger and diverse training set and, if possible, to improve estimation accuracy further by incorporating a series of simple correction factors. We also evaluated the contributions of melting temperature (T-m) and molecular weight (MW). Measured values of water solubility, log K-ow and T-m (solids only) were available for all compounds in the training set (n = 1,450). The best equation for this dataset included log K-ow, T-m, MW, and 12 correction factors as independent variables, with r(2) = 0.970, SD = 0.409, ME = 0.313. Statistics for an independent validation set of 817 compounds were consistent with these results: r(2) = 0.902, SD = 0.615, ME = 0.480. We found that T-m contributed significantly to estimation accuracy for solids; addition of MW also increased accuracy; measured values of log K-ow, and T-m produced more accurate solubility estimates than did estimated values; and the new method outperformed other widely used general-purpose equations based on log K-ow.