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Don’t You Mean logP …not logD?
Posted by: Antony Williams in ChemSpider Chemistry, ChemSpider ServicesCopyright©2007 Antony Williams
If you have examined the predicted physchem properties associated with a structure on ChemSpider you will see something of this nature, on occasion. Notice that there is a logP value but there is also a logD value..in fact two values, one at pH 5.5 and one at pH 7.4. These chosen values were representative of typical physiological pH values of interest. But what IS logD?
Let’s visit the Wikipedia definition of both logP and logD to start:
logP - The partition coefficient is the ratio of concentrations of un-ionized compound between the two solutions. To measure the partition coefficient of ionizable solutes, the pH of the aqueous phase is adjusted such that the predominant form of the compound is un-ionized. The logarithm of the ratio of the concentrations of the un-ionized solute in the solvents is called log P
logD- The distribution coefficient is the ratio of the sum of the concentrations of all forms of the compound (ionized plus unionized) in each of the two phases. For measurements of distribution coefficient, the pH of the aqueous phase is buffered to a specific value such that the pH is not significantly perturbed by the introduction of the compound. The logarithm of the ratio of the sum of concentrations of the solute’s various forms in one solvent, to the sum of the concentrations of its forms in the other solvent is called Log D. In addition, log D is pH dependent, hence the one must specify the pH at which the log D was measured. Of particular interest is the log D at pH = 7.4 (the physiological pH of blood serum). For un-ionizable compounds, log P = log D at any pH.
With these definitions in mind what would we expect for an ionizable compound such as Zyrtec shown below?
The curve below shows the logD as a function of pH for Zyrtec.
At the two pHs of interest what are the structures of the ionized species? See below:
Why would this be important? In fact it’s crucial in the design of drugs in terms of how they act in the body across the physiological profile exhibited by the human body. But, I’m not going to tell you the story…instead I am going to point you to an article “The Rule of Five Revisited: Applying Log D in Place of Log P in Drug Likeness Filters”. This was one of the most accessed articles published in Molecular Pharmaceutics in 2007. It’s featured on the Most Accessed Articles website here.
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December 13th, 2007 at 12:34 am
logP isn’t as useful to me as logD, especially when I’m dealing with amphoteric compounds in chromatography. I had a separation a couple of weeks ago where I was dealing with a compound that had both a carboxylic acid and an amine goup on it. I usually develop separations at high pH or low pH, rarely neutral, and so the compound is always going to be ionized and this will preclude the use of logP. Since you know the pH of your separation beforehand, it is more informative to deal with logD instead of logP.