Estimation of Molecular Linear Free Energy Relationship Descriptors by a Group Contribution Approach. 2. Prediction of Partition Coefficients

A previously published method for the prediction of molecular linear free energy relationship descriptors is tested against experimentally determined partition coefficients in various solvent systems. Sets of partition data between water and octanol, cyclohexane, and chloroform were taken from the literature. For each set of partition data used, r2 values ranged from 0.8 to 0.9 and RMS errors from 0.7 to 1.0 log unit, comparable to errors obtained with previously published models for octanol-water partition. Modified solvation equations for water-octanol and water-cyclohexane partition are presented, and their implications discussed. The possibility of applying the current approach to a wide range of solvation and transport properties is put forward.

[1]  Harpreet S. Chadha,et al.  Hydrogen bonding. 32. An analysis of water-octanol and water-alkane partitioning and the delta log P parameter of seiler. , 1994, Journal of pharmaceutical sciences.

[2]  M. Abraham,et al.  The use of characteristic volumes to measure cavity terms in reversed phase liquid chromatography , 1987 .

[3]  A. Ghose,et al.  Atomic Physicochemical Parameters for Three‐Dimensional Structure‐Directed Quantitative Structure‐Activity Relationships I. Partition Coefficients as a Measure of Hydrophobicity , 1986 .

[4]  R. Collander,et al.  On lipoid solubility. , 1947, Acta physiologica Scandinavica.

[5]  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.

[6]  Michael H. Abraham,et al.  Scales of solute hydrogen-bonding: their construction and application to physicochemical and biochemical processes , 2010 .

[7]  M. Abraham,et al.  The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship. , 1999, Journal of pharmaceutical sciences.

[8]  Michael H. Abraham,et al.  Hydrogen bonding: XVII. The characterisation of 24 gas-liquid chromatographic stationary phases studied by Poole and co-workers. including molten salts, and evaluation of solute-stationary phase interactions , 1991 .

[9]  A. Ghose,et al.  Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragmental Methods: An Analysis of ALOGP and CLOGP Methods , 1998 .

[10]  W. C. Still,et al.  Semianalytical treatment of solvation for molecular mechanics and dynamics , 1990 .

[11]  Harpreet S. Chadha,et al.  Hydrogen bonding. 33. Factors that influence the distribution of solutes between blood and brain. , 1994, Journal of pharmaceutical sciences.

[12]  A. Leo,et al.  Correlation and estimation of gas-chloroform and water-chloroform partition coefficients by a linear free energy relationship method. , 1999, Journal of pharmaceutical sciences.

[13]  A. Leo.  CALCULATING LOG POCT FROM STRUCTURES , 1993 .

[14]  P Buchwald,et al.  Octanol-water partition: searching for predictive models. , 1998, Current medicinal chemistry.

[15]  Bernard Testa,et al.  Intermolecular Forces Expressed in 1,2-Dichloroethane/Water Partition Coefficients: A Solvatochromic Analysis , 1997 .

[16]  N el Tayar,et al.  Partitioning of solutes in different solvent systems: the contribution of hydrogen-bonding capacity and polarity. , 1991, Journal of pharmaceutical sciences.

[17]  Shaomeng Wang,et al.  Estimation of aqueous solubility of organic molecules by the group contribution approach. Application to the study of biodegradation , 1992, J. Chem. Inf. Comput. Sci..

[18]  Shaomeng Wang,et al.  Computer Automated log P Calculations Based on an Extended Group Contribution Approach , 1994, J. Chem. Inf. Comput. Sci..

[19]  James A. Platts,et al.  Estimation of Molecular Linear Free Energy Relation Descriptors Using a Group Contribution Approach , 1999, J. Chem. Inf. Comput. Sci..

[20]  Donald G. Truhlar,et al.  omnisol: Fast Prediction of Free Energies of Solvation and Partition Coefficients , 1998 .

[21]  David E. Leahy,et al.  Model solvent systems for QSAR. Part 3. An LSER analysis of the ‘critical quartet.’ New light on hydrogen bond strength and directionality , 1992 .