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Specialty Chemistry Forums => Biochemistry and Chemical Biology Forum => Topic started by: orgo814 on September 21, 2014, 04:05:32 PM

Title: Acidity
Post by: orgo814 on September 21, 2014, 04:05:32 PM
Trying to determine in which compound would the think group be the most acidic: cysteine, N-acetylcysteine, or Cysteinemethylester

Would the N-acetyl be lowest because it has two carbonyl a having more electron withdrawing groups? Confused..
Title: Re: Acidity
Post by: Dan on September 21, 2014, 05:24:13 PM
Quote from: butlerw2 on September 21, 2014, 04:05:32 PM
in which compound would the think group be the most acidic

What's a "think group"?
Title: Re: Acidity
Post by: salteen on September 21, 2014, 06:38:58 PM
I'm guessing you mean the thiol group?  Silly autocorrect...

Sure, electron-withdrawing effects adjacent to the thiol will definitely improve its acidity.  But I'm not sure a N-acetyl group would be the most withdrawing (consider the protonation states of cysteine at pH 7).
Title: Re: Acidity
Post by: orgo814 on September 21, 2014, 08:13:15 PM
Yup! Autocorrect problem...

And I just can't see why cysteine methylester would make the SH more acidic than N acetyl. I know it's not just regular cysteine.
Title: Re: Acidity
Post by: salteen on September 21, 2014, 08:45:38 PM
Again, you have to consider the protonation states of the ionizable groups on the molecule. At pH 7 and with no acetyl group, the amine will be protonated and bear a formal positive charge - this is a strong electron withdrawing feature, which you were right to consider originally.  That positive charge won't be present with the n-acetyl group, so the thiol will be less able to ionize.

So, for cysteine vs cysteine methyl ester, what will be the overall charge of the molecule in each case with the deprotonated thiol? One of these is much more stable. Try drawing out both examples.
Title: Re: Acidity
Post by: orgo814 on September 22, 2014, 12:36:26 AM
The methylester?
Title: Re: Acidity
Post by: Dan on September 22, 2014, 03:17:10 AM
Quote from: butlerw2 on September 22, 2014, 12:36:26 AM
The methylester?

Can you explain why?
Title: Re: Acidity
Post by: orgo814 on September 22, 2014, 09:30:10 AM
OCH3 is less easily made basic so that the NH3+ can easily stabilize the SH negative charge after it's deprotonated?
Title: Re: Acidity
Post by: salteen on September 22, 2014, 11:14:20 AM
That's correct.  Deprotonation of the thiol will also cancel out the positive charge of the amine, giving the molecule a net 0 charge in the case of the methyl ester. 
Title: Re: Acidity
Post by: Dan on September 22, 2014, 01:33:31 PM
Quote from: salteen on September 22, 2014, 11:14:20 AM
Deprotonation of the thiol will also cancel out the positive charge of the amine, giving the molecule a net 0 charge in the case of the methyl ester.

I doubt the -NH3+/-S- zwitterion is a major form in solution (pKa of the amino acid methyl ester -NH3+ ≈ 7, whereas pKa of -SH ≈ 10).

I would argue that for cysteine and N-Ac-cysteine, SH deprotonation would occur after COOH and -NH3+ deprotonation - meaning that SH deprotonation forms a bis(anion) in these cases.

Contrast that with cysteine methyl ester - what is the overall charge of the species you are forming from SH deprotonation in this case?