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 de-protonates the carboxylic acid):1

amino acid and zwitterion

The (neutral) zwitterion is the form amino acids exist in solution. Depending on the pH, however, two other forms exist (with non-zero charge as anion or 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 zwitterion is the amino acid 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 (in comparison with 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 [0], [1], [2]) is shown in form of the corresponding ionization fractions aj = [j]/CT:

ionization fractions of glycine and carbonic acid

Titration Curves. The titration curves displays what happens to the amino acid glycine (with four different values of amount CT) as you change the pH by adding either a strong acid (HCl) or a strong base (NaOH).

titration curves of glycine

The calculations are done with the analytical formulas presented here or in the pdf. The dots in the right diagram are numerical calculations with aqion.

Buffer Capacity and 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). 

[last modified: 2018-02-04]