Zwitterions

• A zwitterion is a molecule or ion that contains both positive and negative charges within the same molecule, making it electrically neutral.
• It is also known as an inner salt or dipolar ion.
• The term "zwitter" is derived from the German word "zwitterhaft", which means hermaphrodite or hybrid.
• Zwitterions are typically found in amino acids, peptides, and proteins, and they have unique properties that make them important in various fields such as biology, medicine, and materials science.

Properties of zwitterions

Electrically neutral: Zwitterions have both a positive and negative charge within the same molecule, which cancels out the charges and makes the molecule electrically neutral.

Amphipathic: Zwitterions have both polar and nonpolar regions within the same molecule, which makes them soluble in both polar and nonpolar solvents. This property makes them important in the development of surfactants and detergents.

pH dependent: The ionization state of zwitterions is dependent on pH, with the relative concentration of the acidic and basic groups changing as the pH changes. This property is important in biological systems, as it allows zwitterions to act as both acids and bases and participate in a variety of chemical reactions.

High melting and boiling points: Zwitterions typically have higher melting and boiling points than their nonionic counterparts, due to the strong ionic interactions between the positive and negative charges within the molecule.

High stability: Zwitterions are typically more stable than their ionic or nonionic counterparts, due to the cancellation of charges within the molecule.

Chiral: Many zwitterions are chiral, which means they exist in two mirror-image forms. This property is important in the development of chiral catalysts and drugs.

Synthesis methods of zwitterion

Amidation: One of the most common methods for synthesizing zwitterions is through the amidation of an amine and a carboxylic acid. This reaction results in the formation of a peptide bond, which is the basis for the formation of amino acids and proteins. The reaction can be catalyzed by various reagents, such as carbodiimides, which activate the carboxylic acid group and facilitate the reaction.

Salt formation: Another common method for synthesizing zwitterions is through the formation of salts. This can be achieved by reacting an acidic and a basic functional group in the same molecule, such as an amino acid, with an appropriate base or acid. The resulting salt will have both positive and negative charges, making it a zwitterion.

Enzymatic reactions: Enzymes can be used to catalyze the formation of zwitterions in biological systems. For example, the enzyme carbonic anhydrase catalyzes the reaction between carbon dioxide and water to form bicarbonate, which is a zwitterion.

Heterocyclic compounds: Certain heterocyclic compounds, such as imidazolium salts, can also act as zwitterions. These compounds can be synthesized by reacting an amine with a carboxylic acid, followed by a cyclization reaction to form the heterocyclic ring.

Direct synthesis: Zwitterions can also be synthesized through direct synthesis methods, such as the reaction between an isocyanate and an amine, which results in the formation of a zwitterionic urea derivative.

Applications of zwitterions

Zwitterions have a wide range of applications in various fields due to their unique properties. Here are some of the key applications of zwitterions:

Drug design: Zwitterions are important in drug design because they have improved solubility and bioavailability compared to their charged or uncharged counterparts. Zwitterionic drugs also have longer half-lives in the body, leading to improved therapeutic effects.

Separation and purification: Zwitterions can be used in chromatographic separations and purification processes due to their amphipathic nature, which allows them to interact with both polar and nonpolar solvents.

Materials science: Zwitterions are important in the development of materials with improved properties, such as hydrogels, polymers, and coatings. Zwitterionic materials have high biocompatibility and are resistant to fouling and biofouling, making them useful in biomedical and environmental applications.

Surfactants and detergents: Zwitterionic surfactants and detergents have unique properties, such as high biocompatibility and low toxicity, which make them suitable for use in personal care and cleaning products.

Biomedical applications: Zwitterions have been used in various biomedical applications, such as drug delivery, tissue engineering, and biomaterials. Zwitterionic coatings can also prevent protein and cell adhesion, which can be useful in the development of implantable medical devices

Analytical chemistry: Zwitterions can be used as mobile phases in liquid chromatography and as additives in mass spectrometry, due to their high stability and solubility in both polar and nonpolar solvent.

Why amino acid is called zwitterions?

Amino acids are zwitterions because they contain both a basic amino group (-NH2) and an acidic carboxyl group (-COOH) in the same molecule. In a neutral solution, the amino group can accept a proton (H+) to become positively charged, while the carboxyl group can donate a proton to become negatively charged. As a result, the amino acid molecule as a whole has both positive and negative charges, making it a zwitterion.

The formation of a zwitterion in an amino acid molecule occurs due to the presence of a hydrogen atom in the alpha-carbon position (-Cα-) between the amino and carboxyl groups. This hydrogen atom is slightly acidic and can dissociate to form a hydronium ion (H3O+). The negative charge on the carboxyl group can then interact with the hydronium ion, while the positive charge on the amino group can interact with a hydroxide ion (OH-), resulting in the formation of a zwitterion.

What amino acids is zwitterions?

All naturally occurring amino acids, except for glycine, are zwitterions at neutral pH. This includes alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

In a neutral pH solution, the amino group of these amino acids will be protonated, giving it a positive charge, while the carboxyl group will be deprotonated, giving it a negative charge. The overall charge on the molecule will be neutral, as the positive and negative charges cancel each other out.

However, at higher or lower pH values, the amino acid may become fully charged or uncharged depending on the pH conditions. For example, at low pH values, the amino group may become fully protonated, resulting in a positively charged amino acid, while at high pH values, the carboxyl group may become fully deprotonated, resulting in a negatively charged amino acid.

Why is zwitterion called internal salt ?

A zwitterion is often referred to as an internal salt because it contains both a positively and negatively charged group within the same molecule, which can neutralize each other, resulting in an overall neutral charge. This is similar to how an ionic compound such as table salt (NaCl) has both positively and negatively charged ions that are attracted to each other, resulting in an overall neutral compound.

In the case of a zwitterion, the positive and negative charges are usually located on separate functional groups within the same molecule. For example, in the case of an amino acid, the amino group (-NH2) has a positive charge at neutral pH, while the carboxyl group (-COOH) has a negative charge. These charges can interact with each other through electrostatic forces, resulting in a neutral molecule. Because the charges are internal to the molecule, rather than being on separate ions like in a salt, it is called an internal salt.

Is there any relation between isoelectric point and zwitterions?

Yes, there is a relationship between the isoelectric point (pI) and zwitterions. The isoelectric point is the pH at which a molecule has a net charge of zero, and it is an important property of zwitterions.

At the isoelectric point, the positive and negative charges on the zwitterion are equal in strength, and they cancel each other out, resulting in a net charge of zero. This occurs because the pH of the solution is such that the carboxylic acid group (-COOH) and the amino group (-NH3+) are both partially protonated, resulting in a net zero charge. This means that the molecule is no longer a zwitterion at the isoelectric point, but rather it exists as a neutral species.

The isoelectric point of an amino acid is particularly important because it is the pH at which the amino acid exists as a zwitterion. Above the isoelectric point, the amino acid exists primarily in its deprotonated (negatively charged) form, while below the isoelectric point, the amino acid exists primarily in its protonated (positively charged) form.

Thus, the isoelectric point is a critical pH value for zwitterions and plays an important role in their behavior and properties.

How does a proton transfer from -COOH to -NH2 in amino acid  to become a zwitterion?

In an amino acid, the -COOH group is acidic and can donate a proton (H+) to the -NH2 group, which is basic and can accept a proton, forming a zwitterion.

This proton transfer process occurs when an amino acid is dissolved in water or in a polar solvent. However, even in the solid state, some amino acids can exist as zwitterions due to their internal hydrogen bonding.

The -COOH group donates a proton to the -NH2 group, forming an intermediate species, the amino acid with a neutral charge:

H2N-CHR-COOH ⇌ H2N-CHR-COO- + H+

The -COO- group and the -NH3+ group can then be stabilized by internal hydrogen bonding, forming the zwitterion:

H3N+-CHR-COO-

In this zwitterion, the positive charge is delocalized over the nitrogen and the negative charge is delocalized over the carboxylate group, resulting in a neutral net charge.

The proton transfer from the -COOH group to the -NH2 group in amino acids is an example of an acid-base reaction, with the -COOH group acting as the acid and the -NH2 group acting as the base. This reaction results in the formation of a zwitterion, which is a characteristic feature of amino acids.

Difference between a zwitterion and a dipole

Definition: A zwitterion is a molecule that contains both positive and negative charges within the same molecule, typically due to the presence of both an acidic and basic functional group. A dipole, on the other hand, is a molecule that has a separation of electric charge, resulting in a partially positive and partially negative end or side.

Charge distribution: In a zwitterion, the positive and negative charges are localized within the same molecule and are usually in close proximity to each other. In contrast, in a dipole, the partial charges are separated from each other, resulting in an uneven distribution of electron density within the molecule.

Stability: Zwitterions are typically more stable than dipoles because the opposing charges within the molecule neutralize each other, leading to a lower overall energy state. In contrast, dipoles have higher energy due to the separation of charges, making them less stable.

Occurrence: Zwitterions are common in amino acids and other biomolecules, whereas dipoles can occur in a wide range of molecules, including polar molecules such as water and ammonia.

In summary, a zwitterion is a molecule with both positive and negative charges localized within the same molecule due to the presence of both an acidic and basic functional group, whereas a dipole is a molecule with a separation of electric charge, resulting in partial positive and negative charges on different ends or sides of the molecule.