Partition coefficients prediction from octanol

Kerler, F. and J. Schonherr. 1988. Accumulation of Lipophilic Chemicals in Plant Cuticles Prediction From Octanol/Water Partition Coefficients. Arch. Environ. Contam. Toxicol. 17, 1-6. 

Mobility in soil is the potential of a substance or the constituents of a mixture, if released to the environment, to move under natural forces to the groundwater or to a distance from the site of release. The potential for mobility in soil should be given where available. Information on mobility can be determined from relevant mobility data such as adsorption studies or leaching studies. For example, Koc values can be predicted from octanol/water partition coefficients (Kow>. Leaching and mobility can be predicted from models. 

Hence, merely obtaining octanol-water partition coefficient values from various tabulations in the literature can yield a predictive value for k because we have shown that k is directly related to the breakthrough volume, Vr-... 

We will first test the predictive power of this simple nonempirical model on chlorobenzenes and PAHs not included in the original study and on alkylbenzenes, heterocyclic-PAHs, amino- and hydroxy-PAHs, and chlorinated phenols by comparing our predictions with the corresponding experimental values. The results of this test will then be compared with the corresponding soil sorption coefficients predicted from their water solubility (S ) and/or 1-octanol/water partition coefficients (Kq, )- The first-order molecular connectivity indices of the new set of molecules were calculated and their soil sorption coefficients were predicted from the molecular connectivity model, equation 6. These results are shown in TABLE 1 together with the corresponding experimental soil sorption coefficients. 

An important and predicted penalty which followed from the addition of an extra phenoxy-group to 1 to give 3 was the loss of systemic activity, the result of the increase in partition coefficient [log P (octanol/water) estimated to be about 5.1 for 3 water-solubility (measured) = 0.03ppm]. Thus, solutions of 3, applied as a root drench to a range of cereal and broad-leaved crops, give no protection from fungal infection (spore suspension applied as a foliar spray, 24 hours later), while application of the same solutions via foliar spray provides excellent fungicidal activity. 

The HYBOT descriptors were successfully applied to the prediction of the partition coefficient log P (>i--octanol/water) for small organic componnds with one acceptor group from their calculated polarizabilities and the free energy acceptor factor C, as well as properties like solubility log S, the permeability of drugs (Caco-2, human skin), and for the modeling of biological activities. 

Two approaches to quantify/fQ, i.e., to establish a quantitative relationship between the structural features of a compoimd and its properties, are described in this section quantitative structure-property relationships (QSPR) and linear free energy relationships (LFER) cf. Section 3.4.2.2). The LFER approach is important for historical reasons because it contributed the first attempt to predict the property of a compound from an analysis of its structure. LFERs can be established only for congeneric series of compounds, i.e., sets of compounds that share the same skeleton and only have variations in the substituents attached to this skeleton. As examples of a QSPR approach, currently available methods for the prediction of the octanol/water partition coefficient, log P, and of aqueous solubility, log S, of organic compoimds are described in Section 10.1.4 and Section 10.15, respectively. 

This expression can be used to predict solubiUties from the octanol-water partition coefficients. SolubiUty and data for four oligomeric siloxanes are hsted in Table 14. 

From an analysis of the key properties of compounds in the World Dmg Index the now well accepted Rule-of-5 has been derived [25, 26]. It was concluded that compounds are most Hkely to have poor absorption when MW>500, calculated octanol-water partition coefficient Clog P>5, number of H-bond donors >5 and number of H-bond acceptors >10. Computation of these properties is now available as a simple but efficient ADME screen in commercial software. The Rule-of-5 should be seen as a qualitative absorption/permeabiHty predictor [43], rather than a quantitative predictor [140]. The Rule-of-5 is not predictive for bioavail-abihty as sometimes mistakenly is assumed. An important factor for bioavailabihty in addition to absorption is liver first-pass effect (metaboHsm). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [141, 142]. 

Livingstone, D. J., Ford, M. G., Huuskonen, J. J., Salt, D. W. Simultaneous prediction of aqueous solubility and octanol/water partition coefficient based on descriptors derived from molecular structure. J. Comput.-Aided Mol. Des. 2001, 15, 741-752. 

Haeberlein, M., Brinck, T. Prediction of water-octanol partition coefficients using theoretical descriptors derived from the molecular surface area and the electrostatic potential. J. Chem. Soc. 

Olive oil was the original model lipid for partition studies, and was used by Overton in his pioneering research [518,524], It fell out of favor since the 1960s, over concerns about standardizing olive oil from different sources. At that time, octanol replaced olive oil as the standard for partition coefficient measurements. However, from time to time, literature articles on the use of olive oil appear. For example, Poulin et al. [264] were able to demonstrate that partition coefficients based on olive oil-water better predict the in vivo adipose-tissue distribution of drugs, compared to those from octanol-water. The correlation between in vivo log Kp (adipose tissue-plasma) and log (olive oil-water) was 0.98 (r2), compared to 0.11 (r2) in the case of octanol. Adipose tissue is white fat, composed mostly of triglycerides. The improved predictive performance of olive oil may be due to its triglyceride content. 

Winters and Lee134 describe a physically based model for adsorption kinetics for hydrophobic organic chemicals to and from suspended sediment and soil particles. The model requires determination of a single effective dififusivity parameter, which is predictable from compound solution diffusivity, the octanol-water partition coefficient, and the adsorbent organic content, density, and porosity. 

Nevertheless, Absolv gave us five additional parameters to work with. What is more, we used ALOGP, the predicted octanol/water partition coefficient also calculated by Absolv. We combined these descriptors with CLOGP, CMR and those from HYBOT. Forward step-wise regression gave Eq. (7) ... 

Wang, L., Zhao, Y., Hong, G. (1992) Predicting aqueous solubihty and octanol/water partition coefficients of organic chemicals from molar volume. Environ. Chem. 11, 55-70. 

Generally, it is clear how Kd can be predicted for organic hydrophobic pollutants which obey a linear isotherm relationship. First, the organic carbon partition coefficient (i. e.,K0C) is predicted based on either solubility or the octanol-water partition coefficient (K0Vf). Then based on an estimate of the organic carbon fraction in the fine and coarse sediments/soils, Kd can be estimated from Eqs. (a and b) (Table 1). 

The measurement of the solubility of drugs in polar and non-polar media is very important in the pharmaceutical field. One method proposed to describe this solubility is the partition coefficient between octanol and water. The mathematical calculation of an octanol-water partition coefficient from values for functional groups was first proposed by Hansch et al. as Hansch s n constants,1 and was later developed by Rekker as hydrophobic fragmental constants (logP).2 This method was further improved by the use of molecular connectivities.17 The prediction of logP values can be performed by either a computer program or by manual calculation. For example, approximate partition coefficients (log P) have been calculated by Rekker s method ... 

The octanol/buffer represents a partition coefficient between two bulk phases it is less affected by the structure of the analyte and therefore it cannot be used to predict the exact value of liposome membrane-to-buffer Xp, which is also affected by the geometry of the analyte (41 4). However, it is accepted and established that the octanol-to-buffer can help to predict transmembrane passive diffusion (40). In the case of liposomes such as Doxil, in which the internal aqueous phase (intraliposome aqueous phase) is different from the external liposome aqueous medium due to large differences in the composition and pH of these two aqueous phases, there are two different liposome membrane-to-aqueous phase partition coefficients this is referred to as asymmetry in the membrane-to-aqueous media partition coefficient. 

The approach to calculate the van der Waals and cavity terms from the molecular surface areas can be used for the calculation of partition coefficients. The results show that for the distribution of hydrocarbons between water and n-octanol the calculated partition coefficient is linear in carbon number. Qualitatively similar data are obtained for the distribution between other solvents and water and the results can be used to predict the retention in liquid>liquid chromatography. On the other hand, if retention in RPC occurs due to reversible binding at the surface of the stationary phase, the significant parameter is not the total surface area of the eiuite but rather the net decrease in the molecular surface area of the stationary phase ligates and that of the eiuite upon binding, i.e., the contact area in the complex. 

The correlation between partition coefficient and chromatographic retention has been examined by many workers in an attempt to predict log F, the logarithm of water-octanol partition coefficient used in establishing structure-function relationships, from retention data or vice versa. The data (92, 203, 215) seem to imply changes in log k are linear in changes in log P but that log k changes more slowly. Some literature data suggest that the retention is directly proportional to the partition coefficient. This apparent equality disappears, however, if the data are recalculated to identical experimental conditions. 

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