General Factorization of Lipophilicity Valid For All Species

We have not yet introduced the influence of the presence of point charges on the lipophilicity of a chemical. Nevertheless, Sections 12.1.1.2 and 12.1.1.3 do warn that the lipophilic behavior of an ionized molecule might be very different from that of its parent neutral compound. Indeed, in order to investigate the balance of forces governing the lipophiUcity of ionized species we must do without Abraham s equations, since they do not exist when ions are considered. Recently, Abraham et al. also demonstrated what had long been perceived intuitively - descriptors for ions are not the same as those for nonelectrolytes [12]. 

To shed light on this topic, we propose a general equation (Eq. 5) that can be applied to all electrical species and all partitioning systems [3]  

The I term is of particular relevance since, in anisotropic media such as liposomes and artiflcial membranes in chromatographic processes, ionic charges are located on the polar head of phospholipids (see Section 12.1.2) and thus able to form ionic bonds with ionized solutes, which are therefore forced to remain in the nonaqueous phase in certain preferred orientations. Conversely, in isotropic systems, the charges fluctuate in the organic phase and, in general, there are no preferred orientations for the solute. Given this difference in the I term (but also the variation in polar contributions, less evident but nevertheless present), it becomes clear that log P in anisotropic systems could be very different from the value obtained in isotropic systems. 

Equation (5) is of more academic than practical use, but demonstrates the critical role that the introduction of a molecular charge has on the lipophilicity of drugs and drug candidates, which often bear an ionization center and may thus be partially or completely ionized at physiological pH. 

Some may argue that, in practical terms, we do not often have to do with log P , but rather with log This is true, but for the use of log in mathematical 

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