[GeLe5000]

Hello.

Does someone know what is responsible for the low pKa of Omeprazole (2,8 on Wikipedia, French page) ? It's lower than chloroacetic acid !

In vain I look at the molecular structure, I can't see where from these protons can come ?

[Arkcon]

There's a detailed explanation right here:  https://en.wikipedia.org/wiki/Omeprazole#Chemistry

Furthermore, in the structure you have pictured, do you see some hydrogens that should be very eager to leave?

[GeLe5000]

That's the point, I don't see any proton eager to leave. There's one on a Nitrogen, but it would leave a negative charge on it. And then ? It is not explained on the Wikipedia page. If a delocalization of the charge follows, I don't see what structure it will give.
Or would the molecule react with hydroxyl ions present in water and displace the reaction   2 H2O -> H3O+ + OH- ?
Since there's no pKa value given on the English Wikipedia page, I wonder if the value given on the French page is not erroneous.

[Arkcon]

The H₃CO- groups, how are they holding together?

[ETA] I see I though those groups had a different structure than the wikipedia molecule suggests.  However, there are some resonance structures in the wikipedia article that suggest how H+ can be held.

[GeLe5000]

I measured the pH from a capsule containing 40 mg Omeprazole. At a concentration of 1,4 10-3 M (the solubility limit in water), with a pKa = 2,8, the pH should be 3. With a universal indicator I get 6-7. Thus it is not the acid I thought it was.

[clarkstill]

OK, i'm unfamiliar with the french language version of wikipedia. This source:

http://capsugel.com/media/library/formulation-of-proton-pump-inhibitors.pdf

gives two plausible pka values for omeprazole of 3.98 and 8.7, for deprotonation of the protonated pyridinium and benzimidazolium respectively. i.e. it isn't neutral omeprazole that has a low pH, rather it is its various protonated conjugate acids that form when it is placed in a protic environment.

Hope this makes sense.

[GeLe5000]

Thank you clarkstill.

The lowest pKa is 4, instead of 2,8. That's a big difference. Moreover I read a solubility of 0,15 mg/l instead of 0,5 mg/l on the French Wikipedia page. That's also a big difference. I'll be more careful with Wikipédia, in the case of sophisticated molecules.