The n-Octanol-Water Partition Constant

Finally, with respect to the H-acceptor properties of the solvents (a-term), water and n-octanol are quite similar. Therefore, for a hydrogen-bonding solute like 4-BuPh, the corresponding product, a-(a), is close to zero. This is not the case for the hexadecane-water system where loss of hydrogen bonding in this alkane solvent causes both the H-acceptor and H-donor terms to contribute factors of about 100 to 4-BuPh s value of K.  

For sets of compounds with the same functional group and variations in their apolar structural portion, we can also see that is either constant or varies proportionally to yjw (Fig. 7.2). Thus, for such groups of compounds, we find one-parameter LFERs of the type  

Since %w is more or less equal to for many low solubility compounds (yw ca. 50), we have y,w = (FW Q L))-1. Considering such sets of compounds, we can rewrite Eq. 7-10 as  

Such correlation equations have been derived for many classes of compounds (Table 7.3). These examples illustrate that very good relationships are found when only members of a specific compound class are included in the LFER. One can also reasonably combine compound classes into a single LFER if only compounds that exhibit similar intermolecular interaction characteristics are used (e.g., alkyl and chlorobenzenes aliphatic ethers and ketones polychlorinated biphenyls and polychlorinated dibenzodioxins). 

When properly applied, LFERs of these types may be quite useful for estimating Kiow from YiW or QJ (L). Additionally, these relationships can be used to check new Kiovi and/or Cf (L) values for consistency. 

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When is the n-octanol-water partition constant an acceptable parameter for the quantification of nonspecific membrane toxicity In what situations does it fail ... 

Furthermore, for some cationic surfactants, quantitative structure-activity relationships have been established for daphnids and fish. Increments used in the ECOSAR toxicity estimation software (Syracuse Research Center, freely available from the US Environmental Protection Agency as part of the software EPI Suite) are -0.13 and -0.37 for each carbon atom in monoalkyl quaternary ammonium surfactants in daphnids and fish, respectively. These increments are much smaller than the ones found here. Our increments for the n-alkyl chain in Rj position are more in accordance with increments for CH2 groups in n-octanol/water partitioning constant estimation procedures, which are, e.g., 0.66 and 0.49 in Hansch and Leo s method and Meylan and Howard s method, respectively [20]. This suggests that uptake into the cells is governed by lipophilicity, or maybe more exactly by membrane/water partitioning [21, 22]. 

Table 6.17 Mass fraction (w) and mole fraction (x) solubilities of water in RTILs and of RTILs in water and their n-octanol/water partition constants logP°w at ambient temperatures (specified in the references)... 

The following physico-chemical properties of the analyte(s) are important in method development considerations vapor pressure, ultraviolet (UV) absorption spectrum, solubility in water and in solvents, dissociation constant(s), n-octanol/water partition coefficient, stability vs hydrolysis and possible thermal, photo- or chemical degradation. These valuable data enable the analytical chemist to develop the most promising analytical approach, drawing from the literature and from his or her experience with related analytical problems, as exemplified below. Gas chromatography (GC) methods, for example, require a measurable vapor pressure and a certain thermal stability as the analytes move as vaporized molecules within the mobile phase. On the other hand, compounds that have a high vapor pressure will require careful extract concentration by evaporation of volatile solvents. 

We start, however, with some general thermodynamic considerations (Section 7.2). Then, using our insights gained in Chapter 6, we compare solvent-water partition constants of a series of model compounds for different organic solvents of different polarity (Section 7.3). Finally, because n-octanol is such a widely used organic solvent in environmental chemistry, we will discuss the octanol-water partition constant in somewhat more detail (Section 7.4). 

The use of computer techniques in the correlation of biological activity with substrate physical-chemical properties has received much attention in the area of medicinal chemistry. The use of these techniques, denoted Quantitative Structure Activity Relationships (QSAR), were developed mostly by Hansch and his coworkers eind have been reviewed by Tute te), Purcell et. al. (9) and Dunn (10). These techniques were utilized by Greenberg (1 l) ln the correlation of odor threshold and suprathreshold data with Log P, the log (n-octanol/water partition coefficient). In the same study it was reported that steric and polar effects as measured by the Taft Steric and Polar Constants poorly correlated with odor intensity data. 

Historically Hansch correlated the Hammett o constant and log (n-octanol-water partition coefficient) of phenoxyacetic acids with their plant growth regulator activity producing equation 1 ... 

The log C n-octanol/water partition coefficients (log P) for compounds selected for this study were obtained from those reported by Hansch et. (25), or were calculated from fragmental-constants as reported by Nys and Rekker (26). The Taft Steric (E ) and polar (o- ) constants were obtained from those values reported by Taft (27). 

A mainstay of the classical partition model is the experimental observation that the major thermodynamic driving force for sorption is the hydrophobic effect. The hydrophobic effect results from gain in free energy when non- or weakly-polar molecular surface is transferred out of the polar medium of water 2-4), The hydrophobic effect is manifested by a linear free energy relationship (LFER) between the NOM-normalized partition coefficient (A om) and the w-octanol-water partition coefficient K ) [i.e.. In nom a n + b where a and b are regression constants], or the inverse of the compound s liquid (or theoretical subcooled liquid) saturated water solubility CJ) [i.e.. In AT om = -c In + d. ... 

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 n, 0+, and smeta values were experimentally determined, and the ASA, vdW and log/5 (o/w) were determined in MOE. [n = lipophilicity parameter o+ = Hammett constant for ben-zylic cations smeta = Tafts steric parameter ASA = water accessible surface area vol = van der Waals volume logP (o/w) = log of the octanol/water partition coefficient.]... 

Kishino and Kobayashi (1994) determined the n-octane-water (Kioclw) and n-octanol-water (Kiow) partition constants of a series of chlorinated phenols (see Table below). Plot the log Kioctw values versus the log Kiov/ values of the 13 compounds. Inspect the data and derive meaningfull LFERs of the type Eq. 7-7 for subsets of compounds. Discuss your findings in terms of the molecular interactions that govern the partitioning of the chlorinated phenols in the two different solvent-water systems. 

On the other hand, fluorination can exert an influence on the lipophilicity of organic molecules, particularly at positions adjacent to atoms or groups having n electrons. Hansch constants derived from octanol/water partition coefficients of substituted benzenes (ref. 4) are summarized in Table 1. 

Octanol-water partition coefficient. This parameter is usually reported as log A ow or log Pow- It is defined as the ratio of the equilibrium concentrations of a compound in two phases — water and n-octanol. Water solubihty is the maximum amount of a substance, which can be dissolved in water at equihbrium at a given temperature and pressure. Henry s law constant. The concentration ratio of a substance in water and in the air directly above (i.e., at equilibrium). 

Environmental Chemistry and Toxicology of Polychlorinated n-Alkanes This series of compounds are produced from Cio to C30 with chlorine levels ranging from 30 to 70%. The C10-C13 series are the more important from the environmental perspective. Aqueous solubility, vapor presure, Henry s law constant, and octanol-water partition coefficient are provided along with information on degradation processes. 

Yes, and the predictions are quite good. Two different methods emerge from a host of others and are most commonly used to predict octanol-water partition coefficients for the many organic compounds that exist. One approach is to calculate from a knowledge of structural constants, whereas the second approach requires that a chemical s partition coefficient be measured between a solvent other than octanol and water, Kf, . Kf, can then be calculated from linear regression equations that relate log (for a particular solvent) and log Kf, . Two forms of the structural constant approach are most popular (1) the Hansch n hydrophobic character of... 

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