pKa values

Hi,





I am trying to create a database of all the pKa values of my project compounds but I only need the "most common value" of pKa. I mean I am interested only in the value you are going to get as an experimental data, not all the protonation and deprotonation ones. Is there any way to deduce which is the most common?





I hope somebody will be able to help me with that, thank you!





Pedro

Hi,

Quote:

Is there any way to deduce which is the most common?

The aqueous pK_a value of drug like molecules usually observed by experimental techniques in this range :   2<pKa<12





I hope this helps.














Jozsi

Hi Jozsi,





Thank you, but the problem is that depending on which proton is going to leave the molecule or to be added I get a lot of values. Sometimes 7 or 8 different pKa depending on what I said and sometimes the difference between them is about less than 1: 11.4, 12.2, 11.9...








When comparing with the experimental value I can see "Ah OK! this was the correct value" but not before. My intention is to get some rule to choose the correct one or the most common.





Any ideas?





Thank you and regards, Pedro

Hi,














What kind of options did you adjusted on the pKa control panel: micro or macro mode?

















Jozsi

This is a good point!





Example: 2,3-BUTANEDIOL.





If I select MACRO I get two different values for deprotonation and two for protonation. The red values are the closest ones to the experimental data I have: 15.68 and 14.22 (theorical) and 14.9 (experimental). But if I choose MICRO, for the red values I get the same in both sides of the molecule: 14.52, and this is so close to the 14.9 experimental too.





Should I select MICRO always?





However, if I try with 2-Furanmethanamine, the closer value to the experimental one is one of the blue pKa. So... Im confused again. I still need a "rule" for deciding which pKa value given by the program should I select.





Thanks

Hi,

Quote:

Should I select MICRO always?

   It is better if you select MACRO mode.








   








Jozsi

OK, I will use MACRO but... which pKa value should I take as the most similar  to the experimental one?





Thanks again

Hi,

Quote:

...which pKa value should I take as the most similar  to the experimental one?

The purpose of the MACRO pKa calculation is to estimate the experimental pKa value as good as possible.














Jozsi

Im sorry, but I think my explanation was not good enough. I mean there are different values of pKa in the same molecule. Could you tell me which one is the correct? (the closest to the experimental value, because we know there is only one valid, isn't it?)





Thank you again

Hi,





It depends on which pKa value of the compound was measured in the literature where you obtained the data. Marvin calculates all pKa values, in addition, it indicates which one is acidic, and which one is basic. If you have only a single experimental pKa value for your compound, it doesn't mean there must be no more acidic or basic group in it, it just mean that only that one was measured. If your source does not indicate whether the experimental value is acidic or basic, it means they probably suppose that it isobvious for the reader  In addition, if they measure only one value even if there are more ionizable groups in the structure, they probably do this only because the other groups are not relevant/interesting for their research. So try to find a source where you have enough information to assign the measured value to the appropriate ionizable group.





I also suggest you to read the following page carefully:





http://www.chemaxon.com/marvin/help/calculations/pKa.html





This will probably answer several of your remaining questions.





Best regards,





Akos

Thank you very much for your explanation. I think now I understand what you mean, so I will take into account the experimental conditions for these values.





Best Regards





Pedro