Thread: Titration of an Amino Acid

One of the questions in my Biochemistry book asks when the side chain of Histidine has been completely titrated. It lists the pKa of the side chain as 6.0 and it gives a titration curve and lists several points on the curve. The answer in the book says that point 5 is when the side chain is completely titrated. What I don't understand is that point 5 is at a pH of about 7.5. Wouldn't the pH have to be above 8 before you could consider the side chain to be completely titrated? Am I misunderstanding what it means for something to be fully titrated?

Hi Decessus,
surely you know from the Handerson-Hasselbach equation how to calculate the ratio of a base to its conjugated acid, given the pH:

pKA = pH - log10([A]/[HA])

[A]/[HA] = 10^(pH-pKA)

In your case:

@pH=7.5 --> [A]/[HA] = 10^(7.5-6) = 31.6
@pH=8 --> [A]/[HA] = 10^(8-6) = 100

As you see these two ratios are still finite numbers, one a bit bigger than the other, but you will never see it go to infinite (i.e. no HA left at all).

The real question here is about 'titration', i.e. when is it that you've added a number of moles of base equal to the number of moles of acid you had originally?
This doesn't happen at a fixed pH for an acid with a given pKA, it also depends on the concentration of your solution (OK, in practice it doesn't always depend strongly on the concentration, but in theory it always does).

The usual way to determine the 'end point' of a titration is to look at the 'pH' vs 'volume of base added' curve and find where it has an inflection point (corresponding to a maximum of the first derivative, and a zero of the second derivative).
So your book is probably right.