I have some structures where I used Marvin to generate the major microspecies at pH 2.5.
There are several compounds where the predicted major microspecies is inconsistent with the predicted pKa. There are nitrogen atoms with predicted pKa values ranging from 3.92 to 7.32 and the major microspecies still shows no protonated centers. As far as I can tell from looking at other compounds, if the microspecies is specified at pH 2.5, a center with the a predicted pKa of 2.5 or greater will show as protonated. This is for the first pka as none of these compounds show any protonated centers. Certainly if the first pKa for a compound is over 3.5 it should show as protonated at pH 2.5.
Here is a list of problem compounds, the pKa is given first
The first compound has a predicted pKa of 2.65 and shows as protonated. The rest all have higher predicted pKa values and don't show as protonated. Each of these compounds has at least one alpha beta unsaturated ketone group in a conjugated system with an amine. One can question the predicted pKa since many of these nitrogen atoms will exhibit amide like characteristics because of the conjugated connection to the strongly withdrawing ketone, but at the least the major microspecies predictions should be consistent with the pKa prediction.
Any suggestions here?