I am working with a lipid and I have firm reasons to believe that its pKa is around 8. This lipid is a cationic lipid where the nitrogen is a quaternary amine with two lipid chains and two methyl groups.

Now, my question is that at a pH above the pKa of this lipid, the quaternary ammonium ion should get deprotonated, or basically act as an acid. But the quaternary ammonium cation doesn't have any protons to lose, so what would happen to it? My guess would be it accepts a lone pair and becomes negatively charged.

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    $\begingroup$ You seem to think that the pKa of a quaternary salt is the same as the pKa of any other ammonium salt (ie around 9), but that’s not true. The pKa of something is a direct measure of how easily it’s deprotonated. Ammonium salts like R3NH+ are relatively easy to deprotonate, so their pKas are relatively small. A quaternary ammonium salt having no N-H bonds is not easy to deprotonate, so its pKa is large. Things can certainly happen at high pH values, eg elimination or substitution, but a pH of 14 (for example) is not larger than the pKa of the quaternary salt, and it won’t behave as an acid. $\endgroup$
    – orthocresol
    Apr 30 '18 at 0:03
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    $\begingroup$ If you have "firm reasons" that the $\ce{pK_a}$ is around 8, then acid group must be located at the lipid chains. So what lipid groups are you talking of? $\endgroup$
    – aventurin
    Apr 30 '18 at 6:13
  • $\begingroup$ there is no acid chain. the long chains are long aliphatic chains. with no double bonds or other groups present... my basic question is that in case of a quaternary ammonium ion with no H+ to deprotonate what really happens when pH exceeds its pKa? $\endgroup$
    – ansari
    Apr 30 '18 at 14:26
  • $\begingroup$ You keep saying pKa. What is the pKa of a quaternay ammonium ion? What exactly is the deprotonation you're looking at? $\endgroup$
    – Zhe
    May 1 '18 at 13:21
  • $\begingroup$ hi! its me again. I am trying to find more data on quaternary ammonium ion exchanging their counter ions, like at what pH it is triggered, or in what conditions. or is it possible that above a certain pH the counterions can shield the quaternary ammonium ion from interacting with other species in the solvent.. can someone help with these questions or guide me to some literature regarding this? $\endgroup$
    – ansari
    Aug 20 '18 at 9:00

Amine compounds in which the nitrogen is bound to four carbon atoms through covalent bonds are known as quaternary ammonium salts. They are stable compounds that will not converted back to their relevant amines by treatment with base. Generally, they are very soluble in water because of their ionic nature, and also soluble in commonly used organic solvents due to (long chain) organic substituents (e.g.: phase-transfer catalysts). Because they do not contain a free electron pair on nitrogen, in general, the quaternary ammonium ions are inert towards chemical reactions. Thus, pH changes course only them to change their counter ions.

In fact, not only quaternary ammonium salts are relatively unreactive, but also, they do not diffuse readily across biological membranes when used in medicine, because they exist as permanent cations.

  • $\begingroup$ thank you! my experiments do show that that the cationic lipid retains its charge. but i just needed some explanation as to what could happen in such a scenario. also, how high could be the pKa of the basic nitrogen of the quaternary ammonium salt? maybe my assumption of its pka being 8 was wrong. $\endgroup$
    – ansari
    Apr 30 '18 at 14:29
  • $\begingroup$ There is no exchangeable $\ce{H}$ on Quaternary $\ce{N}$, thus, theoretically, it doesn't have $K_\mathrm{a}$. $\endgroup$ Apr 30 '18 at 15:40

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