pH and pKa

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 pK_a of the molecule and the pH of the solution.

Let AH be an atom group in a molecule.  AH could 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 = pK_a.  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.  pK_a values of amino group, carboxyl group and a few R groups.  This information tells us 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.  pK_a 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 HPO₄^2-.  The chance for HPO₄^2- to lose an additional proton is very small.   Hence, the average charge of a phosphate group is about 1.5 electron charges.