Octanol/water partition coefficients historical

Two approaches to quantify/fQ, i.e., to establish a quantitative relationship between the structural features of a compoimd and its properties, are described in this section quantitative structure-property relationships (QSPR) and linear free energy relationships (LFER) cf. Section 3.4.2.2). The LFER approach is important for historical reasons because it contributed the first attempt to predict the property of a compound from an analysis of its structure. LFERs can be established only for congeneric series of compounds, i.e., sets of compounds that share the same skeleton and only have variations in the substituents attached to this skeleton. As examples of a QSPR approach, currently available methods for the prediction of the octanol/water partition coefficient, log P, and of aqueous solubility, log S, of organic compoimds are described in Section 10.1.4 and Section 10.15, respectively. 

Historically, this is the most popular mathematical approach to QSAR. The major contribution of Hansch analysis is in recognizing the importance of logP, where P is the octanol-water partition coefficient. LogP is perhaps the most important measure of a... 

The fundamental idea of QSAR consists of the possibility of a relationship between a set of descriptors, which are derived from molecular structure, and a molecular response. Within this scope, several molecular descriptors, which discretely parameterize a given molecular set, have been devised. From the early work of Cross [1], where a relationship between toxicity and water solubility was observed, several other parameters have been proposed, such as Hammett s sigma [5], which accounts for electronic effects due to molecular backbone substitution, or the octanol/water partition coefficient [6], widely used to describe lipophilicity. Later on, other frameworks have been formulated in order to include molecular shape, size, polarizability, and many other structural features, also based on the three-dimensional molecular character. A number of reviews have been published [7-9], concerning the historical development, descriptor generation, and their application into the QSAR field. 

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 ... 

At this point in the chapter, you should be familiar with aU these chemical properties except for the partition coefficient. Experimentally, partition coefficient values (P) are determined by measuring the amount of a given substance in each layer of a partition media between water and n-octanol, the latter oil being chosen historically to resemble how a substance might partition between the lipophilic nature of a lipid bUayer or... 

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