# Is there a pH at which all proteins are negatively charged? How can it be determined?

I know that depending on the amino-acid-composition of the peptide the distance to the isoelectric point determines the charge. Is there a universal point at which all proteins are definitely negatively charged?

• $14%Ha, not even misusing MathJax here!$ – Jan Jan 22 '17 at 19:58

Proteins will consist primarily of the 20 proteinogenic amino acids. Among those, lysine and arginine are positively charged at neutral $\mathrm{pH}$ while aspartate and glutamate are negatively charged. All proteins also have an amino terminus which is positively charged at neutral $\mathrm{pH}$ and an acid terminus which is negatively charged.
We don’t need to care about the acidic groups; they are already negatively charged. But if we want a $\mathrm{pH}$ level where the protein is definitely negatively charged, we want to deprotonate all positively charged groups.
The amino groups of the N-terminus and lysine have a $\mathrm{p}K_\mathrm{a}\approx 10$. Thus, raising the $\mathrm{pH}$ value to $\mathrm{pH}\ 12$ should get them fully deprotonated. The guanidinium group of arginine is a little less acidic; $\mathrm{p}K_\mathrm{a} \approx 13.6$ (approximated from the value of unsubstituted guanidinium; value found on Wikipedia). We therefore need to raise the $\mathrm{pH}$ a little bit more for certain deprotonation. If we go to the absolute limits of aquaeous $\mathrm{pH}$ of larger than $14$ (i.e. more than $1~\mathrm{M}\ \ce{NaOH}$) we should get these protonated. However, the two logarithmic units one typically assumes would mean $100~\mathrm{M}\ \ce{NaOH}$ — not possible. We can get the $\mathrm{pH}$ to around $15$, and then that’s the end of it. The fully deprotonated form should be the principal species in solution there, though.