Error in Microspecies Distribution for PABA

The microspecies distribution for p-aminobenzoic acid appears to have the neutral and zwitterion reversed. Mid-pH the zwittterion should be the most abundant species but Marvin shows the neutral as being the most abundant.

Pyridoxine is known to exist primarily as a zwitterion in solution but Marvin shows the major component to be the neutral.

Dear Carls,

Quote:

Mid-pH the zwittterion should be the most abundant species

Why do you think this?





Jozsi

Oops. I meant the zwitterion should be the most abundant species between (mid-point) the 2 macro pKa's, not the neutral.

Dear Carl,

Quote:

Oops. I meant the zwitterion should be the most abundant species between (mid-point) the 2 macro pKa's, not the neutral.

OK. Why do you think that the zwitterion should be the most abundant species ?





Jozsi

This is my assumption regarding PABA (acidic pKa 4.77, basic pKa 2.7). For pyridoxine, I have a reference that states the zwitterion is the predominant species between the 2 pKa's (acidic pKa 8.96, basic pKa 5.0). I'm assuming this is a general phenomenon and not specific to pyridoxine.

Dear Carl,











You can apply the next practical rule:





The zwitterionic form will be the major one if one of these conditions is satisfied:


1. pKa(acidic) < pKa (basic)





or





The difference between the acidic and the basic pKa is small


2. pKa(acidic) ~ pKa (basic)











Pyridoxine


Neither of the above conditions is true for Pyridoxine


pKa(acidic) > pKa (basic)





The difference of the acidic and the basic pKa:


DpKa=4.0;





This pKa difference is very large. Therefore concentration of the zwitterionic form will be very small.








PABA


pKa(acidic) > pKa (basic)





The difference of the acidic and the basic pKa:


DpKa=2.0;





This pKa difference is moderately large, therefore, zwitterionic form will be present at small concentration. (maximum is at the isoelectric point)








Our model


In our model the distribution of the microspecies as function of pH calculated from the ratio of the micro pKa values. See. the attached figures.





Our result obeys to the above practical rule.











Jozsi

Phenylalanine, for example, does not obey these rules (pKa acid 2.6 < pKa base 9.2, delta pKa = 6.6). I can see, however, that the acid will be dissociated and the base protonated througout a significant portion of the pH range. How do you treat these cases? Is it possible for me to calculate the microspecies using Excel, i.e. is there a simple formula?

The reason I ask is I am preparing a conference presentation where I discuss the effect of organic solvents on weak acid and base pKa's and the resulting change in their ionization state. I need to be able to specify the pKa for each group since they change depending on the concentration and type of organic. I can estimate the pKa's but I am unsure of how to calculate the resulting microspecies distributions

Dear Carl,








Sorry, in my previous message I interchanged the "<“ and the ">" symbols. I edited that message even now. Please read once more.





Jozsi

Can I get Marvin to display the micro pKa's its using for these calculations?

Dear Carl,








Yes. You need to set the micro pKa calculation mode on the pKa option panel .





See the attached figure.





Jozsi

I ran this for p-aminobenzoic acid and only get 2 pKas. Shouldn't there be a third pKa for the zwitterion?

Dear Carl,








PABA has 4 microspecies. See the attached figure.








Jozsi

Can I get Marvin to return all micro pKas? PABA has 4, right? neutral to dissociated acid, neutral to protonated base, protonated base to zwitterion and dissocaited acid to zwitterion

Dear Carl,

Quote:

Can I get Marvin to return all micro pKas? PABA has 4, right?

Yes. See the attached figure.





Jozsi

OK, I got it. Use the micro pKa option and change ionization (atom charge) of parent molecule.





Would you be interested in collaborating on future projects?

Did Marvin draw this figure automatically or did you calculate the micro pKas and draw the figure manually?

Isn't the micro pKa 3.9 for the protonated base/zwitterion equilibrium?

disregard last comment.

Does it make sense that the aniline N becomes more basic (stronger base) after the carboxy is deprotonated?

Dear Carl,

Quote:

Would you be interested in collaborating on future projects?

If you have confidential support question you can use this e-mail address:


support _at_ chemaxon.com

Quote:

Did Marvin draw this figure automatically or did you calculate the micro pKas and draw the figure manually?

I drew the figure manually.

Quote:

Does it make sense that the aniline N becomes more basic (stronger base) after the carboxy is deprotonated?

Yes, since the COO(-) group is very weak electron withdrawing group and at the same time the COOH group is a stronger electron-withdrawing group.

















Jozsi