Lipophilicity intrinsic

From these equations it is possible to predict the effective lipophilicity (log D) of an acidic or basic compound at any pH value. The data required in order to use the relationship in this way are the intrinsic lipophilicity (log P), the dissociation constant (pKa) and the pH of the aqueous phase. The overaU effect of these relahonships is the effechve hpophilicity of a compound, at physiological pH, is approximately the log P value minus one unit of hpophilicity, for every unit of pH the pKa value is below (for acids) and above (for bases) pH 7.4. Obviously for compounds with mul-hfunchonal ionizable groups the relahonship between log P and log D, as weU as log D as a function of pH become more complex [65, 68, 70]. For diprotic molecules there are already 12 different possible shapes of log D-pH plots. 

The partition coefficient (log P) describes the intrinsic lipophilicitY of the collection of functional groups and carbon skeleton, which combine to make up the structure of the compound, in the absence of dissociation or ionization. Methods to measure partition and distribution coefficients have been described [3,4]. 

The intrinsic lipophilicity (P) of a compound refers only to the equilibrium of the unionized drug between the aqueous phase and the organic phase. It follows that the... 

Use of a hydrocarbon solvent such as cyclohexane can discriminate these compounds either as the only measured value or as a value to be subtracted from the octanol value (Alog P) [19-21]. Unfortunately, cyclohexane is a poor solvent for many compounds and does not have the utility of octanol. Groups which hydrogen bond and attenuate actual membrane crossing compared to their predicted ability based on octanol are listed in Figure 1.4. The presence of two or more amide, carboxyl functions in a molecule will significantly impact on membrane crossing ability and will need substantial intrinsic lipophilicity in other functions to provide sufficient hydrophobicity to penetrate the lipid core of the membrane. 

None of these methods gives a perfect prediction, particularly because H-bonding potential needs to be overlaid over intrinsic lipophilicity. For this reason Lipinski s rule-of-five becomes valuable in defining the outer limits in which chemists can work [9]. Lipinski defined the boundaries of good absorption potential by demonstrating that poor permeability is produced by ... 

The partition coefficient refers to the intrinsic lipophilicity of the drug, in the context of the equilibrium of unionized drug between the aqueous and organic phases. If the drug has more than one ionization center, the distribution of species present will depend on the pH. The concentration of the ionized drug in the aqueous phase will therefore have an effect on the overall observed partition coefficient. This leads to the definition of the distribution coefficient (log D) of a compound, which takes into account the dissociation of weak acids and bases. 

It can be seen that combining this equation with equation 1 gives an equation relating the distribution to the intrinsic lipophilicity (log P), the pKa of the molecule and the pH of the aqueous phase ... 

Iridium complexes are intrinsically lipophilic, so they are easily taken up by cells but tend to give nonspecific localization, mainly staining the cytoplasm [109-114], Intracellular concentration and localization studies have been mostly done by Lo et al. whose review of the field is quite exhaustive [%]. 

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