[dun13203171]

Hi guys I am looking at a compound (Tolmetin) with two pKa values, it consists of the functional groups RCOOH, Pyrole, ketone and a benzene.

Are the two pKa values related to the fact this compound can donate two protons, one from the carboxylic acid and one from the pyrolle. If so how do you know what functional group each pka value refers to?

Also in terms of pH, if pH of a solution= the pka value for the compounf, then 50% of the compound will be ionised. In the cae of a compound with two pKa values, how should this be interpreted?

Moving onto Log-P, if this compound had a log p of say 0.7, how would this be interpreted and does it have a relation to pKa or pH? I have not learned about logP yet but read about it recently but would like to hear how to relates to pKa and pH. From what I gathered, log p refers to the ratio of drug concentrations in oil and aqueous phases of a mixture at equilibrium, log p values greater than one, show better lypophilicity and greater absorption rates in terms of pharmaceutics and sub zero log p values, the reverse.

I would appreciated input.

many thanks

[Borek]

Are the two pKa values related to the fact this compound can donate two protons

Yes.

If so how do you know what functional group each pka value refers to?

Educated guess.

Also in terms of pH, if pH of a solution= the pka value for the compounf, then 50% of the compound will be ionised. In the cae of a compound with two pKa values, how should this be interpreted?

50/50 at pH=pKa is only a simplification of a more universal formula describing the ratio of the concentrations of the acid and its conjugate base, that you can relatively easily derive from the dissociation constant definition. Then you will have ratio of both forms governed by a given pKa in terms of pH and pKa - and you will be able to write set of equations, one for each dissociation equilibrium.

[dun13203171]

50/50 at pH=pKa is only a simplification of a more universal formula describing the ratio of the concentrations of the acid and its conjugate base, that you can relatively easily derive from the dissociation constant definition. Then you will have ratio of both forms governed by a given pKa in terms of pH and pKa - and you will be able to write set of equations, one for each dissociation equilibrium.
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Thanks for your reply borek.

So if you had the pH of the solution and your two pka values for the compound, you can use the HH equation to calculate each inidividually to determine percent ionised of the functional group each pka relates to. In the case of the compound I am looking at, I would say it is the carboxylic acid  has the pka of 3 and the pyrole has the pka of 8.

Sound good?

[Borek]

So if you had the pH of the solution and your two pka values for the compound, you can use the HH equation to calculate each inidividually to determine percent ionised of the functional group each pka relates to. In the case of the compound I am looking at, I would say it is the carboxylic acid  has the pka of 3 and the pyrole has the pka of 8.

Sounds reasonable.