Prediction of partition coefficient

Platts, J. A., Abraham, M. H., Butina, D., Hersey, A. Estimation of molecular linear free energy relationship descriptors by group contribution approach. 2. Prediction of partition coefficient. J. Chem. Inf. Comput. Sci. 2000, 40, 71-80. 

Otherwise, prediction of partition coefficient from the known physical properties of the solute and solvents have been developed by Taft, Abraham, Kamlet, and coworkers [207-210]. They have introduced solvatochromic parameters to assess the intermolecu-lar forces governing the partition mechanisms of neutral organic solutes nonspecific... 

Ruepert, C., Grinwis, A., Govers, H. (1985) Prediction of partition coefficients of unsubstituted polycyclic aromatic hydrocarbons from C18 chromatographic and structural properties. Chemosphere 14, 279-291. 

Covers, H., Ruepert, C., Stevens, T.]., and van Leeuwen, C.]. Experimental determination and prediction of partition coefficients of thioureas and their toxicity to Photobacterium phosphoreum, Chemosphere, 15(4) 383-393, 1986. Govindarajan, M. and Sabarathinam, P. Effect of some inorganic salts on the ternary liquid-liquid equilibria of the water + 4-methyl-2-pentanone + propanoic or butanoic acid at 35 °C, / Chem. Eng. Data, 42(2) 402-408, 1997. 

Yamagami, C., Takao, N., and Fujita, T. Hydrophobicity parameter of diazines. 1. Analysis and prediction of partition coefficients of monosubstituted diazines, Quant Struct.-Act Relat, 9(4) 313-320, 1990. 

Another area where this intermediate level of moieties has been invoked is the use of molecular fragments to predict certain physical properties of molecules (Lyman, 1982). In one example, the prediction of partition coefficients as a measure of lipophilicity is steadily evolving in several laboratories (see below). The central theme of these efforts is the dissection of a molecule into fragments followed by an evaluation of their individual contribution to the physical property. From there a simple summation of contributions (i.e. increments), mitigated by a variety of factors encoding constitutive properties, is made to model the property (Rekker, 1977 Hansch and Leo, 1979). 

Govers, H., et al., Experimental Determination and Prediction of Partition Coefficients of Thioureas and Their Toxicity to Photobacterium phosphoreum. Chemosphere, 1986 22, 383-393. 

Govers, H., Ruepert, C., Stevens, T.J., van Leeuwen, C.J. (1986) Experimental determination and prediction of partition coefficients of thioureas and their toxicity to photobacterium phosphoreum. Chemosphere 15, 383-393. 

P. Meyer and G. Maurer, Correlation and Prediction of Partition Coefficients of Organic Solutes Between Water and an Organic Solvent with a Generalized Form of the LSER. / ml, Eng. Chem. 

Harris, M.J., Higuchi, T., and Rytting, J.H. Thermodynamic group contributions from ion-pair extraction equilibriums for use in the prediction of partition coefficients correlation of surface area with group contributions. 7. Phys. Chem. 1973, 77, 2694-2703. 

Bodor, N., Huang, M.-J. and Harget, A. (1994). Neural Network Studies. Part 3. Prediction of Partition Coefficients. J.Mol.Struct.(Theochem), 309,259-266. 

Devillers J, Domine D, Guillon C, Bintein S, Karcher W. Prediction of Partition coefficient (logPoct) using autocorrelation descriptors. SAR QSAR Environ Res 1997 7 151-72. 

Different approaches have been published regarding the prediction of partition coefficients on the basis of physicochemical parameters of compounds [26-29], These authors described algorithms for the estimation of blood-air and tissue-blood partition coefficients. The most important descriptor for blood-tissue partitioning appears to be lipophilicity and can be described as a function of blood and tissue composition with regard to the lipid and water fractions. Charged molecules do not easily pass membranes passively however, weak bases appear to interact with the charges present at the hydrophilic moieties of phospholipids and can be transferred over the membranes in this way [28]. 

Prediction of partition coefficient and toxicity for benzaldehyde compounds by their capacity factors and various molecular descriptors. Chemosphere, 42, 899-907. 

Hou, T.-J. and Xu, X. (2003) ADME evaluation in drug discovery 2. Prediction of partition coefficient by atom-additive approach based on atom-weighted solvent accessible surface areas. /. Chem, Inf, Comput. Sci., 43, 1058-1067. 

FIGURE 15.2. Prediction of partition coefficients for sodium dodecyl sulfate micellar systems using separate MLR for each database (a) and a single MLR for all databases (b). Databases (O) data compiled by Sprunger et al. (74) and ( ) by Quina et al. (75) for distribution between water and SDS ( ) data compiled by Kelly et al. (25) and ( ) by Poole and Poole (30) using MEKC. 

Partition coefficients are relatively simple to measure, at least in principle. However, the devil is in the details and certain aspects demand sufficient attention that rapid throughput methodologies have not yet been successfully developed to cover a broad range of partitioning. Several recent reviews of experimental methods provide an abundance of practical information on the accurate determination of partition coefficients (22, 23). Indeed, some of the motivation to develop reliable predictions of partition coefficient lies in the fact that measurement is often time-consuming and challenging (24). 

Huuskonen, J. J., Villa, A. E. P., and Tetko, I. V. (1999) Prediction of partition coefficient based on atom-type electrotopological state indices. J. Pharmaceut. Sci. 88, 229-233. 

Based on the explicit treatment of the most important intermolecular interactions (i.e., steric and electrostatic), 3D-QSAR techniques have flourished in the field of ligand—receptor interactions.Because of the interconnection between recognition forces and intermolecular interactions encoded in lipophilicity (Figure 1), the benefits of these techniques in the prediction of partition coefficients from the 3D structure were explored. 

Yamagami C, Takao N, Fujita T (1991) Hydrophobicity parameter of diazines. II analysis and prediction of partition coefficients of disubstituted pyrazines. J Pharm Sci 80 772-777... 

Factor analysis can also be used for the prediction of partition coefficients, because the description of the regular mixtures contains a model similar to the basis of factor analysis. With this description, the partition coefficient can be split into one part, which depends only on the phase system and another part which depends only on the solute. 

Although broad observations on the different partitioning behaviour of compotmds such as naphthalene and glucose have been made since the later years of the nineteenth century, it was only in the 1960s that careful quantitative measurements allowed more confident predictions of partition coefficients to be made for compounds for which they were previously unknown. Log P for benzene between octanol and water (the most commonly quoted solvent pair, as described above) is 2.13. The value for toluene (methylbenzene) is 2.79, so the extra -CH2-contributes 0.66. The value of log P for ethylbenzene is 3.45, so the extra -CH2- again contributes 0.66. With some provisos, it is found that the contribution of a specific molecular fragment to log P is more or less constant. This is discussed in more detail in Chapter 9. 

Revelli, A.-L. Mutelet, F. Jaubert, J.-N. (2010a). Prediction of partition coefficients of organic compounds in ionic liquids Use of a linear solvation energy relationship with parameters calculated through a group contribution method. Ind. Eng. Chem. Res., 8,49, 3883-3892. 

---