Subject octanol-water partition

In a recent study of twenty disperse and solvent dyes, data for water solubility, octanol/ water partition coefficient, entropy of fusion and melting point were subjected to regression analysis. Complicating factors such as impurities, polymorphism, tautomerism, polarisation and hydrogen bonding precluded the development of reliable predictions of solubility and partition coefficient. Anthraquinone dyes exhibited much lower entropy of fusion than many of the azo dyes [64,65]. 

The octanol-air partition coefficient (KOA) has played an important role in the study of plant-air partitioning. At the end of the 1980s, when interest in this subject started to grow, octanol was already well established as a model for the partitioning properties of organic carbon and lipids in aquatic systems. Several researchers borrowed from this experience and postulated that the partitioning properties of the hydrophobic or lipid-like portions of plants also could be modelled using octanol (Schramm et al., 1987 Paterson and Mackay, 1989 McLachlan et al., 1989). Since the partner phase was air, the octanol-water partition coefficient could not be used and it became necessary to define an octanol-air partition coefficient. 

There have been a number of solvent systems utilized in the measurement of the partition coefficient (Livingstone 2003). By far the most commonly used in the last few decades has been the octanol-water solvent pair. The octanol-water partition coefficient is the most commonly measured and applied in QSAR analysis, and it will be the subject of this discussion. By convention the logarithm to the base 10 of the partition coefficient is taken, and known as log or log P. In a series of compounds, a higher log Kow represents more hydrophobic compounds (i.e., more soluble in lipid), and a lower log Kow represents more hydrophilic compounds (i.e., more water soluble). 

The octanol-water partition coefficient of a chemical can be directly measured however, the measurement is not an easy one since the concentration of a hydrophobic organic chemical in the water-rich phase will be very low (i.e., in the parts per million or parts per billion range, where accurate measurements are difficult). Further, the measurement can be subject to appreciable error because if any grease or extraneous organic matter is present in the equipment, a hydrophobic chemical will be absorbed from the water phase, resulting in an erroneously low concentration in that phase tand a high octanol-water partition coefficient). 

In recent years there has been a notable increase in research on structure-activity relationships (SARs), also called quantitative structure-activity relationships (QSARs), used to assess the toxicity of substances for which there are few experimental data. This approach involves establishing mathematical relationships derived from computer modeling, based on known toxicity data of similar (or dissimilar) types of compounds, octanol-water partition coefficients, molar connectivity index values, and other parameters. A detailed discussion on this subject is beyond the scope of this book. 

The concept of measuring such rates is not new, particularly in the pharmaceutical field. Van de Waterbeemd [14] measured rates of transfer of various drugs from octanol to water and empirically related these rates to the partition coefficient. Similarly Brodin [15], using a different experimental method, obtained rates of transfer for another series of compounds between cyclohexane and water. The rotating diffusion cell has been introduced for similar purposes [16-18]. It is necessary to look into the broader background of liquid-liquid interfacial kinetics, in order to illustrate aspects of the issues under consideration. The subject has been reviewed in part by Noble [19]. 

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