Octanol/water partition coefficients overview

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. 

The purpose of this review is to summarize the conditions used to derive chromatographic lipophilicity indices, to appraise associated difficulties, and to provide an overview of their relation with octanol-water partition coefficients. In this aspect, both techniques will be discussed in parallel. 

Overviews of QSAR studies for aquatic toxicity of chemicals which show narcosis are extensively discussed in several publications [93,94]. At first sight, it is quite remarkable that QSAR equations for all kinds of different species are so similar. On the other hand, the explanation is rather simple. It is generally accepted that the mechanism of narcosis is not a very specific process and each compoimd has the same intrinsic activity. In other words the external concentration of a compound at a fixed effect (e.g. narcosis or death) is only a fimction of the probability of a compound to reach its site of action. For many chemicals for which bioaccumulation is not influenced by biotransformation reactions, this probability is correlated to the octanol-water partition coefficient (K ) and this explains directly the correlation between and the external effect concentrations. 

An overview of the application of the following Eqs. 8-12 for QSAR-estimation is given in the flow chart in Fig. 3. The three QSARs for baseline toxicity towards green algae, water, and fish that we used are listed in Table 2. They are based on the octanol-water partition coefficient logfCow and are of the form given in Eq. 9 ... 

Figure 3 Ro5 descriptor space summary of the NIH chemical probes. Rule-of-five overview molecular weight (MW), computed octanol/water partition coefficient (ClogP S) and polar surface area (PSA) for the 64 chemical probes, colored by their qualitative score (see Fig. 2).

The confusion between these two characteristics is common in medicinal chemistry. It comes from the usual empirical measurement of the lipophilicity, which is the logarithm of the partition coefficient between 1-octanol and water (log P). This parameter gives a representative overview of a compound absorbed by a lipidic membrane, an essential datum in medicinal chemistry. It is often considered that the higher the log P value is, the more lipophilic the compound is. Acmally, the log P value is only a measurement of relative solubility. Considering that the solubility of a fluorinated substance decreases more in water than in octanol, this measurement leads one to think that fluorinated compounds are more lipophilic. Actually, this represents the relative lack of affinity of fluorinated compounds for both phases. 

---