What are the pKa values of histidine? (This point will be the pH of 1/2 neutralization)
The amino acid histidine has three acidic groups of pKa's 1.82 (carboxylic acid) 6.04 (pyrrole NH) and 9.17 (ammonium NH). Histidine can exist in four forms, first one (A) having three extra protons, the second (B) having two extra protons, the third (C) having one extra proton and the fourth (D) completely deprotonated. Any of these forms prevail depending on the solution pH, from acidic pH to basic pH. Starting from the most acidic pH, we can imagine that as we add base, the most acidic proton is removed first (COOH), then the pyrrole NH then finally the amino NH. These take us through each of the forms in turn.
At pH < 1.82, A is the dominant form.
In the range 1.82 < pH < 6.02 B is the dominant form.
In the range 6.02 < pH < 9.17 C is the dominant form, and
when pH > 9.17, D is the major form in solution.