Biological group contributions

We can now consider the place of special chemicals in the lives of these organisms. Some of these chemicals link different organisms and others act within individual species. Chemicals in the first group participate directly in the biological chain between acorns and ticks. Those in the second group contribute to a particular species success and so influence these interactions indirectly. All the chemicals are a normal part of these creatures lives and all have a meaningful place here. We begin with oaks and then deal with the animals. 

In an independent publication, Free and Wilson (1964) formulated their mathematical model. This model describes the biological activity in a logarithmic scale as the sum of the biological activities of the reference compound and the group contributions of all substituents that are attached to various positions of this molecule (Kubinyi 2002) ... 

Log 1/C = Ea + i (ai are the group contribution of the individual substituents X to the biological activity values and p, is the calculated biological activity of a reference compound, most often the unsubstituted analogue). 

Solubility data of biological compounds taken from literature are considered in this work. Different thermodynamic models based on cubic equations of state and UNIFAC are used in the correlation of experimental data. Interaction parameters are obtained by group contribution approach in order to establish correlations suitable for the prediction of the solid solubility. 

Group contribution methods search for relationships between structural properties and a physico-chemical or biological response based on the following models ... 

Structure/Response Correlations, Hansch analysis, Hammett equation, Free-Wilson analysis. Linear Solvation Energy Relationships, Linear Free Energy Relationships, group contribution methods, substituent descriptors, extrathermodynamic approach, and biological activity indices. 

Additive (group contribution) methods have a long tradition of successful use in predicting the properties of both ordinary molecules and macromolecules (polymers). They have formed the backbone of the quantitative structure-activity relationships (QSAR) [1,2] used to predict the chemical reactivity and the biological activity of molecules in medicinal and agricultural chemistry. They have also been used extensively in many quantitative structure-property relationships (QSPR) developed for the physical and chemical properties of polymers. 

In the following decades, various a scales were derived for different systems and several attempts were made to derive such relationships also for biological activities of organic compounds. Bruice et al. [10] formulated group contributions to biological activity values in a series of thyroid hormone analogs, which may be considered as a first Free-Wilson-type analysis. Zahradnik and Chvapil [11] and Zahradnik [12,13] tried to apply the concept of the Hammett equation also to biological data (Eq. (5)) ... 

Free-Wilson analysis can be used for a first inspection of biological activity data [30-32]. The values of the group contributions indicate which physicochemical properties might be responsible for the variations in biological activity values and whether nonlinear lipophilicity-activity relationships are involved. Free-Wilson contributions can be derived from Hansch equations (e.g., by Eq. (18) from Eq. (14), or by Eq. (19) from Eq. (15)) [30] ... 

Free and Wilson gave a more general description of this mathematical (empirical) model in 1964 (30). According to their method, the defined biological response (BR) of a congener in a homologous series is equal to the sum of the substituent group contributions to the activity plus that of the parent structure (/x), Equation 5. For example, Purcell has used... 

While the success of QSAR analyses may be taken as sufficient evidence for the additivity of group contributions to biological activity values, the following question arises are these group contributions more or less constant from one system to the other or do they depend on the choice of the compounds and/or the biological system ... 

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