Limitations Free Wilson analysis

By its definition the Free Wilson analysis is limited to linear additive structure-activity relationships (its application to nonlinear relationships and the combination with Hansch analysis to a mixed approach are described in chapter 4.3). A detailed discussion of the scope and limitations of the Free Wilson model is given in refs. [390, 391] some applications are discussed in chapter 8. 

Scope and Limitations of Hansch and Free-Wilson Analysis... 

It has been suggested (9) that both the Hansch and the Free-Wilson methods be used in QSAR analysis, but in general the methods are used exclusively. The Hansch method is best applied to a congeneric series in which a systematic change in a single substituent is made. The need for reliable physicochemical parameters for the substituents on the studied molecules is usually restrictive. The Free-Wilson method, on the other hand, is not limited by the physicochemical parameters (since only indicator variables are used) but needs large variations in substitution patterns to avoid singularities. Clearly the methods compliment each other. 

Like the continuous physico-chemical descriptor Z variables, indicators of the presence or absence of certain substructures have also been treated by multiple regression analysis. As modified by Fujita and Ban (Seydel and Schaper, 1979), this group contribution method can be a useful alternative to the LFER approach, if only limited knowledge is available about the relevant molecular properties or no uniform physico-chemical descriptors for the various compounds in the data set are accessible. For activities and properties of compounds that may be attributed to the occurrence of certain substructures in the molecules (e.g. biodegradation section 4.8), Free-Wilson-type substructure models have their major application in environmental sciences. 

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