Hansch and Leo

Physical and Chemical Properties. The physical/chemical properties of endosulfan are sufficiently well characterized to enable assessment of the environmental fate of the compound (Budavari 1996 Coleman and Dolinger 1982 EPA 1982c, 1987b Hansch and Leo 1995 HSDB 1999 Metcalf 1995 NIOSH 1997 Sitfig 1980 Suntio et al. 1988 Tomlin 1994). The relative persistence of the two isomers and the potential for conversion from one isomer to another may also deserve further study. 

Attempts have been made to apply the structure-activity concept (Hansch and Leo 1995) to environmental problems, and this has been successfully applied to the rates of hydrolysis of carbamate pesticides (Wolfe et al. 1978), and of esters of chlorinated carboxylic acids (Paris et al. 1984). This has been extended to correlating rates of biotransformation with the structure of the substrates and has been illustrated with a number of single-stage reactions. Clearly, this approach can be refined with the increased understanding of the structure and function of the relevant degradative enzymes. Some examples illustrate the application of this procedure ... 

Hansch and Leo [13] described the impact of Hpophihdty on pharmacodynamic events in detailed chapters on QSAR studies of proteins and enzymes, of antitumor drugs, of central nervous system agents as well as microbial and pesticide QSAR studies. Furthermore, many reviews document the prime importance of log P as descriptors of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties [5-18]. Increased lipophilicity was shown to correlate with poorer aqueous solubility, increased plasma protein binding, increased storage in tissues, and more rapid metabolism and elimination. Lipophilicity is also a highly important descriptor of blood-brain barrier (BBB) permeability [19, 20]. Last, but not least, lipophilicity plays a dominant role in toxicity prediction [21]. 

The octanol-water partition coefficient Kow is widely used as a descriptor of hydrophobicity. Variation in /fow is primarily attributable to variation in activity coefficient in the aqueous phase (Miller et al. 1985) thus, the same correlations used for solubility in water are applicable to /fow. Most widely used is the Hansch-Leo compilation of data (Leo et al. 1971, Hansch and Leo 1979) and related predictive methods. Examples of Kow correlations are ... 

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