Computation of partition coefficients

The universal relevance of partitioning in the assessment of chemicals provoked early attempts to estimate the respective values directly from the 

A more general approach, also based on the assumption of an additive, constitutive nature of partition coefficients, was proposed by Rekker (1977). The log of a compound corresponds to the sum of lipophilicity contributions of its constituents. The structures are virtually decomposed into sub-structural fragments (f ) with individual contributions (a ) to the lipophilicity of the entire molecules. Additionally, correction terms (b ) account for interactions between different fragments in the molecules (Fj)  

Principally the same fragment (f.) and factor (F ) approach was used by Hansch and Leo (1979), proceeding in a methodologically different way. Rekker used a large database with heterogeneous chemicals whereas Leo and Hansch used a rather small set of especially selected compounds to obtain the 

Detailed tabulations of fragment and factor values are given by Hansch and Leo (1979), Rekker (1977) and Lyman (1990b) together with elaborated instructions and examples. 

Alternative approaches to the calculation of log P values from fragment contributions comprise solvent regression equations - extrapolations from 

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Chou, J.T., Jurs, PC. (1979) Computation of partition coefficients from molecular structures by a fragment addition method. In Physical Chemical Properties of Drugs. Medical Research Series, Vol. 10, Yalkowsky, S.H., Sindula, A.A., Valvani, S.C., Editors, Marcel Dekker, New York. pp. 163-199. 

Chou, J.T. and Jurs, P.C. Computer-assisted computation of partition coefficients from molecular structures using fragment constants, / Chem. Info. Comp. Sci., 19(3) 172-178, 1979. 

The similar accuracies of different well-parameterized continuum models implies that they will also perform similarly for the computation of partition coefficients, and that has proven to be the case in most studies to date (see, for example, Bordner, Cavasotto, and Abagyan 2002 and Curutchet et al. 2003b). In Table 11.4 the previously presented SMx results for the chloroform/water partitioning of die methylated canonical nucleic acid bases are compared to results from die MST-ST/HF/6-31G method, and also to purely electrostatic results obtained using a multipole expansion SCRF method. As the latter does not include any accounting for non-electrostatic effects, its performance is significantly degraded compared to the other two. 

Chou, J. T., and P. C. Jurs, Computer-Assisted Computation of Partition Coefficients from Molecular Structure Using Fragment Constants. J. Chem. Inf. Comput. Sci., 1979 19,172-178. 

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. 

Klopman, G., Iroff, L. D. Calculation of partition coefficients by the charge density method. J. Comput. Chem. 1981, 2,157-160. 

Blood-tissue uptake rates (l< ) can often be approximated from data at early (t < 10 minutes) time points in IV studies, provided the blood has been washed from the organ (e.g., liver) or the contribution from blood to the tissue residue is subtracted (fat). High accuracy is not usually required since these parameters can be optimized to fit the data when they are used in more complex models. Tissue-blood recycling rates (A y) and residence times can be computed from partition coefficients if estimates of uptake rates are available. 

Richards, N., Williams, P. B., and Tute, M. (1991) Empirical methods for computing molecular partition coefficients. I. Upon the need to model the specific hydration of polar groups in fragment based approaches. Int. J. Quant. Chem. 18, 299-316. 

Klopman, G., and S. Wang, A Computer Automated Structure Evaluation (CASE) Approach to Calculation of Partition Coefficient. J. Comput. Chem., 1991 12,1025-1032. 

Klopman, G., J.-Y. Li, S. Wang, and M. Dimayuga. 1994. Computer Automated log P Calculations Based on an Extended Group Contribution Approach. J. Chem. Inf. Comput. Sci. 34, 752-781. Klopman, G., and S. Wang. 1991. A Computer Automated Structure Evaluation (CASE) Approach to Calculation of Partition Coefficients. J. Comput. Chem. 8 1025-1034. 

Klopman, G. and Iroff, L. (1981). Calculation of Partition Coefficients by the Charge Density Method. J.Comput.Chem., 2,157-160. 

Klopman, G., Namboodiri, K. and Schochet, M. (1985). Simple Method of Computing the Partition Coefficient. J.ComputChem., 6,28-38. 

Huuskonen JJ, Livingstone DJ, Tetko IV. Neural network modeling for estimation of partition coefficient based on atom-type electrotopological state indices. I Chem Inf Comput Sci 2000 40 947-55. 

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. 

Mopman, G. and Wang, S. (1991) A computer automated structure evaluation (CASE) approach to calculation of partition coefficient. /. Comput. Chem., 12, 1025-1032. 

For solving heterogeneous models it is necessary to take into account the effect of such processes as dissolution and mineral formation, surface complex formation and ion exchange. That is why beside stability constants of complexes in water it is necessary to have values of ion exchange coefficients, solubility products and also surface acidity and constant of surface complex formation for individual minerals. For nonpolar and chemically passive components are needed values of partition coefficients or solubility. Due to the shortage of these data and complexity of computations at... 

Kossoy, A. D., Risley, D. S., Kleyle, R. M., and Nurock, D. (1992). Novel computational method for the determination of partition coefficients by planar chromatography. Anal. Chem. 64 1345-1349. 

To compute the partition coefficient, you can use the lattice model for the chemical potential of s in each liquid. According to Equations (15.15) and (15.16),... 

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