Zwitterion

An amino acid contains both acidic (carboxylic acid fragment) and basic (amine fragment) centres. The isomer on the right is a zwitterion.

The zwitterion is formed in two stages. In stage 1, a proton is transferred from the carboxyl group to a water molecule.

${\displaystyle H_{2}N(R)CO_{2}H+H_{2}O\leftrightharpoons H_{2}N(R)CO_{2}^{-}+H_{3}O^{+}}$

In stage 2 a proton is transferred from the hydronium ion to the amine group

${\displaystyle H_{2}N(R)CO_{2}^{-}+H_{3}O^{+}\leftrightharpoons H_{3}N^{+}(R)CO_{2}^{-}+H_{2}O}$

The reverse reactions occur in the reverse order. Overall, the reaction is an isomerization reaction

${\displaystyle H_{2}N(R)CO_{2}H\leftrightharpoons H_{3}N^{+}(R)CO_{2}^{-}}$

The ratio of the concentrations of the two species in solution will be independent of pH as it is equal to the value of the equilibrium constant for the isomerization reaction.

${\displaystyle K={\frac {[H_{3}N^{+}(R)CO_{2}^{-}]}{[H_{2}N(R)CO_{2}H]}}}$

[X] signifies the concentration of the chemical species X at equilibrium. It is generally assumed that K>1, that is, that the zwitterion is the predominant amino acid isomer in solution. One explanation based on theoretical analysis is that the neutral form is less stable itself but becomes stabilized by hydrogen bonding with water molecules.[2] Analysis of neutron diffraction data for glycine showed that it was in the zwitterionic form in the solid state.[3] Theoretical calculations have been used to show that zwitterions may also be present in the gas phase for some cases different than the simple carboxylic acid-to-amine transfer.[4]

The pK_a values for deprotonation of the common amino acids span the approximate range 2.15 ± 0.2. This is also consistent with the zwitterion being the predominant isomer that is present in an aqueous solution. For comparison, the carboxylic acid propionic acid, RCO₂H (R=CH₃CH₂), has pK value of 4.88.

• 
  Sulfamic acid isomers, with the zwitterion (right)
• 
  Anthranilic acid
• 
  Structure of H₄EDTA

Sulfamic acid crystallizes in the zwitterion form.[5]

In crystals of anthranilic acid there are two molecules in the unit cell. One molecule is in the zwitterion form, the other is not.[6]

In the solid state, H₄EDTA is a zwitterion with two protons having been transferred from carboxylic acid groups to the nitrogen atoms.[7]

pyridoxal phosphate

Although the equilibrium, in solution, between a compound and its zwitterion isomer cannot be studied experimentally, some insight may be gained from the results of theoretical calculations. A good example is provided with pyridoxal phosphate, a form of vitamin B6. A tautomeric equilibrium was predicted to obtain in an aqueous solution of this compound, favouring the zwitterion in which a proton is transferred from the phenolic -OH group to the nitrogen atom.[8]

The compound trimethylglycine, which was isolated from sugar beet, was named as "betaine". Later, other compounds were discovered that contain the same structural motif, a quaternary nitrogen atom with a carboxylate group attached to it via a -CH₂- link. At the present time, all compounds whose structure includes this motif are known as betaines. Betaines do not isomerize because the chemical groups attached to the nitrogen atom are not labile. These compounds may be classed as permanent zwitterions, as isomerisation to a molecule with no electrical charges does not occur, or is very slow.[9]

Other examples of permanent zwitterions include phosphatidylcholines and psilocybin, which also contain a quaternary nitrogen atom, but with a negatively-charged phosphate group in place of a carboxylate group and pulmonary surfactants such as dipalmitoylphosphatidylcholine.

• 
  Trimethylglycine (trivial name betaine)
• 
  Example of a phosphatidylcholine
• 
  Psilocybin
• 
  Lauramidopropyl betaine, the major component of cocamidopropyl betaine

• Azomethine ylide