pKa theophylline

I checked the predicted pKa value of theophylline using the online version of Marvin and received a value of 4.86. This value is muych higher than expected so checked the pKa of the tautomer and found the result more in line with expectation, pKa 1.66.





I was under the immpression that Marvin accounted for tautomers when predicting pKa's.





Any comments?





Carl

Hi Carl,





theophylline has two pKa values: aromatic 'N' pKa= 1.0 and aromatic 'NH' pKa=9.0.








The pKa calculator does not generate the most significant tauotmeric form of the submitted molecule automatically.








In many cases it is simpler if you find out the most stable tauotmeric form by yourself and submit this for the pKa calculator.








On the other hand you can invoke the canonical tauotmeric form and submit this for the pKa calculator.





For this purpose you can use the tautomer generator tool that can generate canonical tautomeric form.








Jozsi