Lipophilicity experimental description

Practical problems in the estimation of the lipophilicity of araliphatic and aliphatic compoimds led to the / hydrophobicity scales of Rekker and Leo/Hansch. However, all such descriptor scales depend on experimental determinations. New molecular descriptors were developed from scratch, starting with the work of Randic, Kier and Hall, i.e. the various molecular connectivity parameters %. Later the electrotopological state parameters and the Todeschini WHIM parameters were added. Whereas topological descriptors are mathematical constructs that have no unique chemical meaning, they are clearly related to some physicochemical properties and are suited to the description of compound similarities in a quantitative manner. Thus, despite several critical comments in the past, they are now relatively widely used in QSAR studies. Only a meaningless and excessive application in quantitative models, as far as the number of tested and included variables is concerned, still deserves criticism. 

It was a century ago that researchers started to study the factors affecting the behaviour of water-oil-surfactant systems but it is only with the introduction of Winsor s R theory (1954) that the formulation effects could be interpreted. Winsor s R theory was the first qualitative description of the formulation, paving the way to an understanding of how intermolecular interactions among the different chemical species present in a system are related to its behaviour. Throughout the following decades, several empirical experimental correlations such as the phase inversion temperature (PIT), semiempirical ones such as the cohesive energy ratio (CER), and models based on thermodynamics such as the surfactant affinity difference (SAD) or the hydrophilic-lipophilic deviation (HLD) [15, 143, 144] led... 

Figure 3.6 Example of a non-linear log PQ -dependent model (Veith, Call and Brooke, 1983) in comparison to experimental data on fish toxicity (log I/LC50 in mmol/1). The bilinear function provides a good description of the activity data for the compounds with log < log Pow(max.) whereas the model is less well defined for the highly lipophilic substances because their data are extremely variable.

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