An extended version of a novel method for the estimation of partition coefficients.

Using the semi-empirical AM1 method, 302 compounds have been studied and equilibrium properties calculated. Functions based on linear combinations of subsets of calculated properties have been fit to the 1-octanol-water partition coefficients. The best such semi-empirical approach function has 18 parameters, has a standard deviation of 0.306, and seems to describe the partition coefficients of the 302 compounds. The predictive power of the function was tested and found to be good. Since this new version is based on a much larger number of, and structurally more varied, compounds and uses an improved, new function, we expect it to be a very useful method to predict partition properties of a wide variety of compounds.

[1]  J. Stewart.  Optimization of parameters for semiempirical methods II. Applications , 1989 .

[2]  Samuel H. Yalkowsky,et al.  Relationships between aqueous solubility and octanol-water partition coefficients , 1980 .

[3]  S H Yalkowsky,et al.  Partition coefficients and surface areas of some alkylbenzenes. , 1976, Journal of medicinal chemistry.

[4]  O. Hutzinger,et al.  Some thoughts on aqueous solubilities and partition coefficients of PCB, and the mathematical correlation between bioaccumulation and physico-chemical properties , 1978 .

[5]  Michele M. Miller,et al.  Relationships between octanol-water partition coefficient and aqueous solubility. , 1985, Environmental science & technology.

[6]  N. Bodor,et al.  A new method for the estimation of partition coefficient , 1989 .

[7]  F. Hirayama,et al.  Partition behavior and ion pair formation of some prostaglandins. , 1978 .

[8]  S. Yalkowsky,et al.  Solubility and partitioning IV: Aqueous solubility and octanol-water partition coefficients of liquid nonelectrolytes. , 1981, Journal of pharmaceutical sciences.

[9]  S. Yalkowsky,et al.  Estimation of the aqueous solubility of some aromatic compounds , 1983 .

[10]  Gilles Klopman,et al.  Calculation of partition coefficients by the charge density method , 1981 .

[11]  C. T. Chiou,et al.  Partition equilibriums of nonionic organic compounds between soil organic matter and water. , 1983, Environmental science & technology.

[12]  D. Leahy,et al.  Intrinsic molecular volume as a measure of the cavity term in linear solvation energy relationships: octanol-water partition coefficients and aqueous solubilities. , 1986, Journal of pharmaceutical sciences.

[13]  Yadu B. Tewari,et al.  Aqueous solubility and octanol/water partition coefficient of organic compounds at 25.0.degree.C , 1982 .

[14]  G. R. Famini,et al.  Solubility properties in polymers and biological media 5: an analysis of the physicochemical properties which influence octanol-water partition coefficients of aliphatic and aromatic solutes. , 1985, Journal of pharmaceutical sciences.

[15]  Michael H. Abraham,et al.  Linear solvation energy relationship. 46. An improved equation for correlation and prediction of octanol/water partition coefficients of organic nonelectrolytes (including strong hydrogen bond donor solutes) , 1988 .

[16]  C. Hansch,et al.  Linear free-energy relationship between partition coefficients and the aqueous solubility of organic liquids , 1968 .

[17]  S. Yalkowsky,et al.  Solubility and partitioning I: Solubility of nonelectrolytes in water. , 1980, Journal of pharmaceutical sciences.

[18]  A. Leo,et al.  Dependence of hydrophobicity of apolar molecules on their molecular volume. , 1976, Journal of medicinal chemistry.

[19]  C Silipo,et al.  Calculation of hydrophobic constant (log P) from pi and f constants. , 1975, Journal of medicinal chemistry.

[20]  A. Leo,et al.  Substituent constants for correlation analysis in chemistry and biology , 1979 .