Tautomer selection for pKa estimation

User afdc6e23db

16-04-2013 15:09:10

am using version 5.12.3 of the Calculator Plugins, to estimate pKa values for
compounds that often have multiple tautomers. Which tautomer is most likely to
give pKa estimates that are close to measured values? I would expect it to be
the major tautomer but, as the ascorbic acid example below shows, this is not
always the case. Measured pKa for ascorbic acid are around 4.1 and 11.6.
Estimated pKa for the input tautomer (left of figure) are pretty close to the
measured values, but estimated pKa for the predicted major tautomer (right) are
not. Is this a bug, or should I use a different tautomer for pKa estimation
than the predicted major tautomer? What tautomer do you use to train the pKa

User 851ac690a0

24-04-2013 12:44:41



Thank you very much for reporting this bug! This is a scoop for me. 

The major tautomeric form of the ascorbic acid is the di-enol form. 

The "1,3 diketo" and the "pyruvate"  are only minor tautomeric forms.    


The bug fix will be available in the next bug fix release in the  5.12.x  (x>3) version.



User afdc6e23db

30-04-2013 15:34:30

Hi Jozsi,

Thank you for your reply. Does this mean that the major tautomer of a compound is most likely to give pKa estimates that are close to experimental values?


ChemAxon 2136dd2f4b

30-04-2013 15:56:28


Yes, that's right.


User 6c619df658

28-05-2013 15:13:12

I've just notice that. thank you