Tetrad of equilibria

The topic of drug partitioning between water and lipids concerns chemical equilibria. For a monoprotic weak acid (and base), the partitioning equilibria may be represented as 

As mentioned in Chapater 3, the law of mass action sets the concentration relations of the reactants and products. So, the equilibrium constants, termed the partition coefficients, are the quotients 

To distinguish partition coefficients of neutral species from ionized species, the notation log PN and log/j/ may be used, respectively, or the symbol C or A may be used as a substitute for superscript /, denoting a cation or anion, respectively. [362], 

It is convenient to summarize the various reactions in a box diagram, such as Fig. 4.1 [17,275,280], illustrated with the equilibria of the weak base, propranolol. In Fig. 4.1 is an equation labeled pA °et. This constant refers to the octanol pKa, a term first used by Scherrer [280]. When the concentrations of the uncharged and the charged species in octanol are equal, the aqueous pH at that point defines p which is indicated for a weak acid as 

Characteristic of a box diagram, the difference between the partition coefficients is equal to the difference between the two pKa values [229,275,280,362]  

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Figure 5.1 Phospholipid membrane-water tetrad equilibria. Only half of a bilayer is shown. [Avdeef, A., Cun Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

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