ATOM FRAGMENT CONTRIBUTION METHOD FOR ESTIMATING OCTANOL-WATER PARTITION-COEFFICIENTS
ATOM FRAGMENT CONTRIBUTION METHOD FOR ESTIMATING OCTANOL-WATER PARTITION-COEFFICIENTS
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DOI：
10.1002/jps.2600840120
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发表时间：
1995-01-01
影响因子：
3.8
通讯作者：
HOWARD, PH
中科院分区：
文献类型：
--
作者：
MEYLAN, WM;HOWARD, PH
通过对1120个化合物的对数正辛醇-水分配系数的多元线性回归，确定了130个简单化学亚结构的原子/碎片贡献值，用于估算有机化合物的对数辛醇-水分配系数。另有1231个化合物被用来确定235个不同亚结构取向的“修正因子”。化合物的对数P是通过简单地将化学结构中出现的所有原子/碎片贡献值和校正因子相加来估计的。对于2351个复合训练集，估计值与实测值的相关系数(P)为0.98，标准偏差(SD)为0.22，绝对平均误差(ME)为0.16个对数单位。该原子/碎片贡献(AFC)方法随后在6055个测量的对数P值的单独验证集上进行测试，这些值未用于推导该方法，得到P为0.943，SD为0.408，ME为0.31.该方法能够对8406个化合物的实验数据集中96%以上的+/-0.8个对数单位内的logP进行预测。由于简单的原子/碎片方法，在AFC方法中不会出现“丢失碎片”(在其他方法中遇到的问题)。从统计学上讲，它优于其他综合评价方法。
Atom/fragment contribution values, used to estimate the log octanol-water partition coefficient (log P) of organic compounds, have been determined for 130 simple chemical substructures by a multiple linear regression of 1120 compounds with measured log P values. An additional 1231 compounds were used to determine 235 ''correction factors'' for various substructure orientations. The log P of a compound is estimated by simply summing all atom/fragment contribution values and correction factors occurring in a chemical structure. For the 2351 compound training set, the correlation coefficient (P) for the estimated vs measured log P values is 0.98 with a standard deviation (SD) of 0.22 and an absolute mean error (ME) of 0.16 log units. This atom/fragment contribution (AFC) method was then tested on a separate validation set of 6055 measured log P values that were not used to derive the methodology and yielded an P of 0.943, an SD of 0.408, and an ME of 0.31. The method is able to predict log P within +/-0.8 log units for over 96% of the experimental dataset of 8406 compounds. Because of the simple atom/fragment methodology, ''missing fragments'' (a problem encountered in other methods) do not occur in the AFC method. Statistically, it is superior to other comprehensive estimation methods.