Zwitterions and Amino Acids

A zwitterion is a molecule with functional groups, of which at least one has a positive and one has a negative electrical charge. The net charge of the entire molecule is zero.

Amino acids are the best-known examples of zwitterions. They contain an amine group (basic) and a carboxylic group (acidic). The -NH2 group is the stronger base, and so it picks up H+ from the -COOH group to leave a zwitterion (i.e. the amine group deprotonates the carboxylic acid):1

amino acid and zwitterion

The (neutral) zwitterion is the usual form amino acids exist in solution. Depending on the pH, there are two other forms, an anion and a cation:

zwitterion with anion and cation

This parallels the behavior of a diprotic acid:

zwitterion vs diprotic acid

with two dissociation steps controlled by two acidity constants K1 and K2.

When an amino acid dissolves in water, the zwitterion interacts with H2O molecules — acting as both an acid and a base. But, unlike simple amphoteric compounds that may only form either a cationic or anionic species, a zwitterion simultaneously has both ionic states.

Glycine vs Carbonic Acid

The simplest amino acid is glycine (NH2-CH2-COOH), which we abbreviate by HGly, or shorter by HA with A- = Gly-. Its structural formula shown above has the shortest side chain R = H. The three species are:

  [0] = [H2A+] =   [H2Gly+] : NH3+-CH2-COOH (glycinium cation)
  [1] = [HA] =   [HGly] : NH3+-CH2-COO- (neutral zwitterion)
  [2] = [A-] =   [Gly-] : NH2-CH2-COO- (glycinate anion)

The two acidity constants (compared to carbonic acid) are:

  glycine: pK1 = 2.35 pK2 = 9.78
  carbonic acid: pK1 = 6.35 pK2 = 11.33

The pH dependence of the three species (abbreviated by [j]=[0], [1], [2]) is shown in the form of ionization fractions aj = [j]/CT:

ionization fractions of glycine and carbonic acid

Titration Curves. The titration curves display what happens to glycine as you change the pH by adding either a strong acid (HCl) or a strong base (NaOH):

titration curves of glycine

In the left diagram, four amounts CT of glycine are considered; the calculations are based on simple analytical formulas.2 The right diagram compares the analytical calculation for CT = 0.1 M (orange curve) with the numerical calculations using aqion (blue dots). The numerical model takes into account the activity corrections and is therefore more accurate.

Buffer Capacity and Buffer Intensity

The mathematical description of buffer capacities and intensities is the same as for common acids (except the offset Z=1). The diagrams below show the buffer capacity (blue titration curve) together with the corresponding buffer intensity β (green) and its derivative dβ/dpH (red). This is done for two cases: infinitely high concentrated glycine and for CT = 500 mM.

buffer capacity and intensity of glycine

The small dots are the zeros of dβ/dpH, which indicate the extrema of the buffer intensity β and mark inflection points of the titration curves. The blue titration curve in the previous left diagram is the same as in the last diagram except that the x- and y-axis are swapped.

More examples for zwitterionic acids are given here.

Remarks & Footnotes

  1. R denotes the side chain (glycine: R = H, alanine: R = CH3, and so on). 

  2. A detailed mathematical description is provided as review (2021) or lecture (2023). 

[last modified: 2023-07-17]