Octanol Water Partition Coefficients

The log M-octanol/water partition coefficient (log represents one of the most informative physicochemical parameters available to medicinal or environmental chemists. It is defined for dilute solutions as the molar concentration ratio of a single species (A) between two phases at equilibrium  

Two different predictive methods to estimate log P iv, were developed within our own Center. Considering the diversity of retrometabolic drug design approaches, such versatility is needed since at different ends of the retrometabolic loop one has to deal with vei7 different molecular structures. 

Molecular orbital calculation-based model (BLOGP) 

Most methods used by medicinal chemists to estimate the partition properties of a compound are so-called fragment contribution methods. The basic idea behind all these methods is quite similar. Molecules are broken down into predefined fragments and their corresponding contributions are summed up to obtain the final log P value based on the following equation  

Here f, represents the fragmental contribution and Oj represents the number of occurrences of fragment type /, Fj represents the contribution and bj represents the number of occurrences of correction factor type j. Understandably, the performance of any such method strongly depends on the definition of its basic fragment library what is and what is not considered as a separate entity on its own. 

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The flic presented contains 11 data items. The header lines arc property names as used by CACTVS [64, 65], and arc sufficiently self-descriptive. For example, E NHDONORS is the number of hydrogen bond donor.s, E SM1LES" is the SMILES string representing the structure of sulfamidc, and E LOGP is the logP value (octanol/water partition coefficient) for this substance. 

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. 

A series of studies has been made by Yalkowsky and co-workers. The so-called general solubility equation was used for estimating the solubility of solid nonelectrolytes [17, 18]. The solubility log S (logarithm of solubility expressed as mol/L) was formulated with log P logarithm of octanol/water partition coefficient), and the melting point (MP) as shown in Eq. (11). This equation generally... 

The octanol—water partition coefficient, which is used as an iadicator of the tendency of an organic chemical to accumulate ia living tissue, was low. This iadicates that naphthalene is unlikely to accumulate ia the body. 

Other evaluations (27,28) of environmental considerations report vapor pressure, water solubiHty, and the octanol/water partition coefficient for trimethylbenzenes. 

Silicones have been detected in water from various rivers and in effluent from wastewater treatment faciUties. They are barely detectable in water from municipal treatment faciUties. Water solubiUty (S) of siUcones has been found to correlate with the octanol—water partition coefficients for a... 

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. 

Table 14. Effect of Siloxane Molecular Weight on Water Solubility and Octanol-Water Partition Coefficient...

In the case of mercaptopropionic acid, biodegradation of 96% was achieved within 28 d ia a closed botde test based oa the consumption of oxygea. The pass level of 60% was reached within 10 d of exceeding the 10% level thus, mercaptopropionic acid can be considered as readily biodegradable. It is not expected to bio accumulate, owing to the low (log P — 0.09) -octanol/water partition coefficient. 

An overview of some basic mathematical techniques for data correlation is to be found herein together with background on several types of physical property correlating techniques and a road map for the use of selected methods. Methods are presented for the correlation of observed experimental data to physical properties such as critical properties, normal boiling point, molar volume, vapor pressure, heats of vaporization and fusion, heat capacity, surface tension, viscosity, thermal conductivity, acentric factor, flammability limits, enthalpy of formation, Gibbs energy, entropy, activity coefficients, Henry s constant, octanol—water partition coefficients, diffusion coefficients, virial coefficients, chemical reactivity, and toxicological parameters. 

Many additional consistency tests can be derived from phase equiUbrium constraints. From thermodynamics, the activity coefficient is known to be the fundamental basis of many properties and parameters of engineering interest. Therefore, data for such quantities as Henry s constant, octanol—water partition coefficient, aqueous solubiUty, and solubiUty of water in chemicals are related to solution activity coefficients and other properties through fundamental equiUbrium relationships (10,23,24). Accurate, consistent data should be expected to satisfy these and other thermodynamic requirements. Furthermore, equiUbrium models may permit a missing property value to be calculated from those values that are known (2). 

Octanol—Water Partition Coefficient. In environmental calculations, the octanol—water partition coefficient, is related to a chemical s Hpophilicity and... 

Once the composition of each equiHbrium phase is known, infinite dilution activity coefficients for a third component ia each phase can then be calculated. The octanol—water partition coefficient is directly proportional to the ratio of the infinite dilution activity coefficients for a third component distributed between the water-rich and octanol-rich phases (5,24). The primary drawback to the activity coefficient approach to estimation is the difficulty of the calculations involved, particularly when the activity coefficient model is complex. 

A sampling of appHcations of Kamlet-Taft LSERs include the following. (/) The Solvatochromic Parameters for Activity Coefficient Estimation (SPACE) method for infinite dilution activity coefficients where improved predictions over UNIEAC for a database of 1879 critically evaluated experimental data points has been claimed (263). (2) Observation of inverse linear relationship between log 1-octanol—water partition coefficient and Hquid... 

By modeling the substance behavior at the interface of two liquid phases, in particular, stationary and mobile phases in liquid chromatography, 1-octanol - water partition coefficients or partition coefficients in... 

Several Hansch-Leo n substituent parameters denved from octanol-water partition coefficients (P), = log p (ce sX) - log P (C H ), are hsted m Table 9... 

Properties of Fluonnated Compounds Table 10. Octanol-Water Partition Coefficients... 

Closely related to water solubility as a polarity measure is the partition coefficient of a substance between water and an immiscible organic solvent. Most commonly the organic solvent is selected to be n-octanol, and the symbol P is given to the octanol/water partition coefficient. Then log P is a quantitative measure of hydro-phobicity and, therefore, of nonpolarity. Table 8-3 gives log P values for many of... 

Table 8-3. Octanol/Water Partition Coefficients of Solvents...

The toxicological or cumulative effect of illicit drugs on the ecosystems has not been studied yet. Moreover, their fate and transport in the environment is to a big extent still unknown. Due to their physical-chemical properties (octanol-water partition coefficient, solubility, etc.) some of them, such as cannabinoids, are likely to bioaccumulate in organisms or concentrate in sediments whereas the rest, much more polar compounds, will tend to stay in aqueous environmental matrices. However, continuous exposure of aquatic organisms to low aquatic concentrations of these substances, some of them still biologically active (e.g., cocaine (CO), morphine (MOR) and MDMA) may cause undesirable effects on the biota. 

The BUSES model provides an estimate of the organic carbon/water partition coefficient (Koc) based on the octanol/water partition coefficient (Kow)- From these data, it is evident that the methyltins are less likely to partition onto organic carbon (in sediments, soils, biota) than are the butyl- and octyltin compormds due to then-lower partition coefficients and higher water solubilities. The 7/oc value can then be used to derive sohds/water partition coefficients in suspended matter, in sediment, and in soil using values of 10%, 5%, and 2% for organie carbon, representing typical organic carbon contents of suspended matter, sediment, and soil, respeetively. 

Swann R, Laskowski D, McCAll P, et al. 1983. A rapid method for the estimation of the environmental parameters octanol/water partition coefficient, soil sorption constant, water to air ratio, and water solubility. Residue Rev 85 18-28. 

Octanol-Water Partition Coefficient (Kq )—The equilibrium ratio of the concentrations of a chemical in TT-octanol and water, in dilute solution. 

An important factor in determining the course of uptake, transport, and distribution of xenobiotics is their polarity. Compounds of low polarity tend to be lipophilic and of low water solubility. Compounds of high polarity tend to be hydrophilic and of low fat solubility. The balance between the lipophilicity and hydrophilicity of any compound is indicated by its octanol-water partition coefficient (K J, a value determined when equilibrium is reached between the two adjoining phases ... 

Connell, D.W. (1994). The octanol-water partition coefficient, Chapter 13 ofVol. 2, in Calow (Ed.). Handbook of Ecotoxicology. Oxford, U.K. Blackwell. 

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