MoBio pH and pKa Chapter 2

A molecule, or an atom group in a molecule, may lose or gain a proton when the molecule is placed in an aqueous solution. The exact probability that a molecule will be protonated or deprotonated depends on the pKa of the molecule and the pH of the solution.

Let AH be an atom group in a molecule. AH may be neutral or charged. After AH loses a proton, it is denoted by A-. The protonation/deprotonation reaction may be written as

From the last equation, we can see that half of molecules will lose protons if they are in a solution with pH = pKa. The higher the pH value, the more likely a molecule will lose a proton. On the other hand, from the definition of pH, we find that the proton concentration of a solution becomes lower at higher pH, thereby capable of accepting more protons. This physical concept is consistent with the result we just obtained from the equation.


Figure 2-A-4. pKa values of amino group, carboxyl group and a few R groups.

This information tells us that in a neutral solution:

  • The carboxyl group is most likely negatively charged.
  • The amino group is most likely positively charged
  • The R group of aspartate and glutamate are most likely negatively charged.
  • The R group of lysine and arginine are most likely positively charged.
  • The R group of tyrosine at pH = 7 is most likely neutral.
  • The R group of histidine has 10% probability to become positively charged at pH = 7, but the probability increases to 50% at pH = 6. Thus, histidine is very sensitive to pH change in the physiological range.

Figure 2-A-5. pKa values of phosphate groups. This information tells us that in a neutral solution H3PO4 is very likely to lose a proton and become H2PO4-. The latter has a 50% chance of losing another proton, becoming HPO42-. The chance for HPO42- to lose an additional proton is very small. Hence, the average charge of a phosphate group is about 1.5 electron charges.