In chemistry, a zwitterion is a neutral molecule that has equal numbers of positive and negative charged functional groups. The charged functional groups connect to the rest of the molecule by covalent bonds.
The zwitterion definition comes from the German word Zwitter, which means “hybrid” or “hermaphrodite.” The name reflects that a zwitterion has equal regions of positive and negative electrical charge. Sometimes zwitterions go by the name “inner salts.” But, this name may lead to confusion because salts contain ionic bonds, while zwitterions contain covalent bonds.
Some molecules are zwitterions only within certain pH ranges. Other molecules only exist as zwitterions and never have uncharged functional groups. These compounds are called permanent zwitterions.
Examples of Zwitterions
- Amino acids: The best-known examples of zwitterions are amino acids. An amino acid has an amino group and a carboxyl functional group. On its own, an amino acid is not a zwitterion, but in aqueous solution the amino group gains a proton (hydrogen atom) and has a positive charge, while the carboxyl group loses a proton and gets a negative charge. This occurs in an isomerization reaction. The zwitterion is neutral overall, but has equal and opposite charged functional groups. At neutral pH in water, there is an equilibrium between the “parent” amino acid and its zwitterion.
H2N(R)CO2H ↔ H3N+(R)CO2– + H2O
At low pH, the amino acid forms a cation. At high pH, it form an anion.
- Betaines: Betaines are permanent zwitterions. Examples of betaines are trimethylglycine and cocamidopropyl betaine.
- Sulfamic acid: Like amino acids, sulfamic acid exists in an all-neutral form and a zwitterion form. Sulfamic acid crystallizes in its zwitterion form.
- Anthranilic acid: Anthranilic acid crystals contain equal amounts of the parent molecule and the zwitterion.
What Is Not a Zwitterion?
In order to understand what zwitterions are, it helps to see examples of what they are not. Molecules that have regions of partial charge are not zwitterions. Salts are not zwitterions. Examples of compounds that are not zwitterions include:
- Water (H2O): Although water is a neutral covalent compound, the hydrogen and oxygen atoms are regions of only partial charge. Water auto-dissociates and forms separate hydronium and hydroxide ions.
- Sodium chloride (NaCl): Sodium chloride and other salts are not zwitterions because they are connected by ionic bonds. Further, they dissociate in water rather than form molecules with regions of positive and negative charge.
- Ammonium chloride (NH4Cl): Ammonium chloride does contain covalent bonds within the ammonium cation, but ammonium connects to chloride via ionic bonds. Ammonium chloride dissociates in water rather than forming a neutral molecule with charged regions.
Zwitterions display certain properties:
- A zwitterion is neutral, but has both positive and negative regions of charge.
- Zwitterions contain covalent bonds.
- Many form from ampholytes that have both acidic and basic functional groups.
- Zwitterions tend to have higher melting points than other molecules of the same size. The charged regions strongly attract other molecules, so it takes more energy to separate them.
- A zwitterion such as an amino acid has an isoelectric point (pI). This the the pH value where the molecule has a neutral charge.
Importance of Zwitterions
Zwitterions have important uses commercially and in nature:
- Biochemistry: For example, phosphatidyl choline is a phospholipid that is an important component of cell membranes. The charged regions give the molecule both hydrophobic and hydrophilic properties.
- Medicine and supplements: Many alkaloids are zwitterions. Their pharmacology depends on their properties. Some supplements, such as L-lysine, are zwitterions. Zwitterions are important in sensors and medical implants.
- Buffers: Some buffers are zwitterions, such as MOPS and HEPES. These buffers do not permeate cell membranes.
- Molecular biology: Zwitterions find use in SDS PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). The main use here is for protein separation.
- Coatings: Zwitterions help prevent bacteria and other organisms from settling onto surfaces. Such coatings occur in medicine and the marine industry.
- Jensen, Jan H.; Gordon, Mark S. (1995). “On the Number of Water Molecules Necessary to Stabilize the Glycine Zwitterion”. Journal of the American Chemical Society. 117 (31): 8159–8170. doi:10.1021/ja00136a013
- Nelson, D. L.; Cox, M. M. (2000). Lehninger, Principles of Biochemistry (3rd ed.). New York: Worth Publishing. ISBN 1-57259-153-6.
- Price, William D.; Jockusch, Rebecca A.; Williams, Evan R. (1997). “Is Arginine a Zwitterion in the Gas Phase?”. Journal of the American Chemical Society. 119 (49): 11988–11989. doi:10.1021/ja9711627. PMC 1364450
- Skoog, Douglas, A.; West, Donald M.; Holler, F. James; Crouch, Stanley R. (2004). Fundamentals of Analytical Chemistry (8th ed.). Thomson/Brooks/Cole. ISBN 0-03-035523-0.