What Is an Amino Acid Zwitterion? The Dipolar Form Explained

What this guide covers

Why does glycine, a molecule with no metal in it and only ten atoms, refuse to melt until the hot plate passes 200 degrees? Most organic molecules that small are liquids or low-melting solids. Glycine is a hard white crystal that breaks down before it melts.

The answer is the zwitterion. In plain terms, an amino acid hands a proton from one end of itself to the other, so it ends up with a plus at one end and a minus at the other. The two charges cancel, and the molecule as a whole is neutral, but each end still pulls hard on its neighbors. That is what makes the crystal behave like a salt.

This guide explains what the zwitterion is, why it is the dominant form near neutral pH, what the solid-state evidence looks like, how the form shifts as pH changes, and how a single amino acid's charge behavior differs from a peptide's. For the five parts of the molecule itself, start with the guide to the parts of an amino acid.

What is an amino acid zwitterion?

An amino acid zwitterion is the form of an amino acid in which the carboxyl group has lost its proton and the amino group has gained one. The carboxyl becomes a carboxylate, written -COO-, and the amino group becomes an ammonium, written -NH3+. One negative charge and one positive charge sit on the same molecule, so the net charge is zero. A species with both a negatively charged group and a positively charged group is what chemists call a zwitterion, from the German word for hybrid.

The proton does not come from outside. It moves within the molecule, from the acidic carboxyl group to the basic amino group, which is why the zwitterion forms even with no water present. The Chemguide teaching site describes it as an internal transfer of a hydrogen ion from the -COOH group to the -NH2 group, and notes that this is the form amino acids hold even in the solid state.

Textbook drawings usually show the neutral form, with -NH2 and -COOH intact. That is a convention. The IUPAC-IUB nomenclature recommendations say their formulas are written in hypothetical forms with the amino groups unprotonated and the carboxyl groups undissociated, and that this should not be taken to imply that those structures represent an appreciable fraction of the amino acid molecules. The drawing is for naming. The zwitterion is what is there.

PubChem keeps the two forms as separate records. Glycine (CID 750) has the formula C2H5NO2 and a molecular weight of 75.07. The zwitterion, recorded as alpha-glycine (CID 5257127), has the same formula and the same weight, and its IUPAC name is 2-azaniumylacetate, which spells out the ammonium and the carboxylate in one word. Same atoms, same mass, different arrangement of one proton.

Why do amino acids exist mostly as zwitterions near neutral pH?

Amino acids exist mostly as zwitterions near neutral pH because the two ionizable groups have pKa values on opposite sides of 7. For glycine, PubChem lists a carboxyl pKa of 2.34 and an amino pKa of 9.60, from the Merck Index, with an IUPAC-compiled value of 2.37 at 20 degrees for the carboxyl group.

A carboxyl group with a pKa near 2.3 is a weak acid, and at pH 7 the solution is more than four units above that pKa. By the usual acid-base arithmetic, nearly every carboxyl group has given up its proton and sits as -COO-. The amino group has a pKa near 9.6, so at pH 7 the solution is more than two units below it, and nearly every amino group holds a proton as -NH3+. Both conditions are true at once. Both charges are present at once. That is the zwitterion.

The pH at which the positive and negative forms balance exactly is the isoelectric point, pI. For an amino acid with one amino group and one carboxyl group, pI is the average of the two pKa values. From the Merck figures, (2.34 + 9.60) / 2 = 5.97, which is our arithmetic. Chemguide gives 6.07 for glycine, 6.11 for alanine and 5.68 for serine. Either way, the number is near 6 rather than 7. Chemguide explains why: the zwitterion is a slightly stronger acid than it is a base, so in pure water a few more molecules lose a proton than gain one, and it takes a touch of acid to even the count.

The companion guide to amino acid pKa values tabulates these numbers for all twenty standard residues, including the side chains that carry a third ionizable group.

What is the evidence from the solid state?

The strongest everyday evidence that amino acids are zwitterions is how they behave as solids. A general chemistry text describes amino acids as colorless, nonvolatile, crystalline solids that melt and decompose above 200 degrees Celsius, and adds that these melting temperatures are more like those of inorganic salts than those of amines or organic acids. That is the point. A molecule of glycine's size with no charges would be expected to melt low. Instead its CRC Handbook entry, recorded in PubChem, reads 290 degrees Celsius with decomposition.

The explanation is the lattice. In a zwitterion crystal, the ammonium end of one molecule sits next to the carboxylate end of the next, and those ionic attractions take far more energy to break than the weak forces between neutral organic molecules. Chemguide makes the same argument and draws the same conclusion: ionic attractions between neighboring zwitterions account for the high melting points given how small the molecules are.

Solubility tells the same story from the other side. Amino acids are generally soluble in water and insoluble in nonpolar organic solvents such as hydrocarbons. Water can surround each charged end and replace the ionic attractions of the lattice. A hydrocarbon cannot, so too little energy is released to pull the crystal apart. Chemguide also notes that water solubility varies with the size and nature of the side chain without an obvious pattern, which is a reminder that the R group modifies a trend set by the zwitterion backbone.

Crystallography adds detail. The stable crystal form of glycine, alpha-glycine, is built from hydrogen-bonded cyclic dimers, according to a 2025 study of glycine nucleation, and glycine crystallizes in more than one polymorph depending on conditions.

How does the zwitterion change with pH?

The zwitterion is the middle of three forms, and pH moves the molecule between them. Add acid, and the carboxylate end of the zwitterion picks up a proton. The molecule now carries -NH3+ and -COOH, a net charge of plus one. Add alkali, and hydroxide removes the proton from the ammonium end. The molecule now carries -NH2 and -COO-, a net charge of minus one.

Electrophoresis is the classic way to see this. In acid solution the positive ion travels toward the cathode. In alkaline solution the negative ion travels toward the anode. At one specific pH the amino acid does not move at all, and that pH is the isoelectric point. Chemguide uses exactly this lack of movement as its definition of pI.

Two things are worth keeping straight. First, the three forms are not switched on and off at sharp pH values. They are equilibria, and a solution a unit or so away from a pKa still holds a measurable share of the neighboring form. Second, the simple three-form picture only holds for amino acids with one amino group and one carboxyl group. Aspartate, glutamate, lysine, arginine, histidine, tyrosine and cysteine each add a side-chain group with its own pKa, and the guide to acidic and basic amino acids walks through those.

How to work out which form dominates at a given pH

For any amino acid and any pH, the dominant form follows from the pKa values. Take glycine at pH 7.4.

1. List the ionizable groups. Glycine has two: the alpha-carboxyl (pKa 2.34) and the alpha-amino (pKa 9.60).
2. Compare the pH with each pKa. At pH 7.4 the solution is 5.06 units above the carboxyl pKa and 2.20 units below the amino pKa.
3. Assign the state of each group. Far above its pKa, an acid group is deprotonated: -COO-. Far below its pKa, a basic group is protonated: -NH3+.
4. Add the charges. One minus and one plus give zero. At pH 7.4 glycine is almost entirely zwitterion.
5. Find the pI if you need it. Average the two pKa values that bracket the neutral form: (2.34 + 9.60) / 2 = 5.97.
6. For a residue with an ionizable side chain, add that pKa to the list in step 1 and repeat. The pI is then the average of the two pKa values on either side of the zero-charge form, which may no longer be the alpha groups.

How does a single amino acid differ from a peptide?

A free amino acid has exactly one amino group and one carboxyl group on the alpha carbon, so it has one zwitterion to talk about. A peptide is different. When amino acids join, the carboxyl of one and the amino of the next are consumed in the peptide bond. The IUPAC-IUB recommendations describe the backbone as the repeating run of C-1, C-2 and N-2 through each residue, with the remainder forming a side chain. Those backbone amide groups carry no charge.

So a peptide has only two alpha groups left that can ionize: the free amino group at the N-terminus and the free carboxyl at the C-terminus. Everything else that carries charge comes from side chains. A dipeptide of two glycines still forms a zwitterion across its two ends. A longer chain with lysines and glutamates inside it can carry several positive and several negative charges at once, and its net charge at a given pH is the sum of all of them.

That is why the isoelectric point of a peptide is a calculation over the whole sequence rather than an average of two numbers. The guide to the peptide isoelectric point shows that calculation step by step, including a worked example. The single-amino-acid case on this page is the building block it starts from.

Where does the zwitterion show up in laboratory work?

The zwitterion is the reason an amino acid dissolves in water and crystallizes as a hard solid, so it sits behind the most routine handling in a peptide laboratory. Three places it matters:

• Mass measurement. The zwitterion and the neutral form have the same formula and the same molecular weight, 75.07 for glycine in both PubChem records. Mass spectrometry reports mass, so a certificate's LC-MS identity result is unaffected by which charge form the molecule held in the vial. The sequence sets the mass; the proton arrangement does not change it.
• Solubility. Water dissolves zwitterions because it can solvate both charged ends. The guide to peptide solubility covers how side chains and pH shift that for a longer chain.
• Separation. Electrophoresis sorts amino acids by the sign and size of their net charge, which pH controls. Any method that depends on charge is a method that depends on where the pH sits relative to the pKa values.

Every certificate LabFirst Peptides publishes reports identity by LC-MS, purity by RP-HPLC on a C18 column and net content as a separate line, each by lot number. None of those results depends on the charge form in the powder, because the mass is the same either way, and the certificate index lists the lots for which a certificate is posted.

Bottom line

An amino acid zwitterion is an amino acid with its carboxyl proton moved onto its amino group: -COO- at one end, -NH3+ at the other, zero net charge. It dominates near neutral pH because the carboxyl pKa is near 2 and the amino pKa is near 9 or 10, so at pH 7 the acid is deprotonated and the base is protonated at the same time. The salt-like melting points and the water solubility of crystalline amino acids are the visible evidence. Acid turns it into a cation, alkali into an anion, and the crossover pH is the isoelectric point, near 6 for the simple amino acids.

FOR LABORATORY AND IN-VITRO RESEARCH USE ONLY. NOT FOR HUMAN OR ANIMAL CONSUMPTION.

Common questions

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Sources

• PubChem compound record: Glycine (CID 750), via PUG REST and PUG View. Formula C2H5NO2 and molecular weight 75.07; pKa values 2.34 and 9.60 (Merck Index) and 2.37 at 20 degrees (Kortum et al., IUPAC); melting point 290 degrees Celsius with decomposition (CRC Handbook, 79th ed.).
• PubChem compound record: alpha-Glycine, the glycine zwitterion (CID 5257127), via PUG REST. IUPAC name 2-azaniumylacetate, formula C2H5NO2, molecular weight 75.07: the zwitterion recorded as a separate compound with the same formula and mass.
• IUPAC-IUB Joint Commission on Biochemical Nomenclature, Nomenclature and Symbolism for Amino Acids and Peptides, section 1 (general considerations). Formulas are written with amino groups unprotonated and carboxyl groups undissociated as a naming convention, which should not be taken to imply those structures represent an appreciable fraction of the molecules; the backbone repeats through C-1, C-2 and N-2 of each residue.
• Ball, Hill and Scott, The Basics of General, Organic, and Biological Chemistry, 18.1 Properties of Amino Acids (LibreTexts). Amino acids are colorless, nonvolatile, crystalline solids melting and decomposing above 200 degrees Celsius; the melting temperatures resemble inorganic salts rather than amines or organic acids, which is why the solid-state and neutral-solution structures are represented with both charges.
• Chemguide, An introduction to amino acids: the zwitterion and physical properties. Internal transfer of a hydrogen ion from -COOH to -NH2; the zwitterion is the form in the solid state; melting and decomposition in the 200-300 degree range; solubility in water and insolubility in hydrocarbons explained by the ionic lattice.
• Chemguide, The acid-base behaviour of amino acids. What happens to the zwitterion when acid or alkali is added, the direction of movement in electrophoresis, the definition of the isoelectric point, and the values 6.07 (glycine), 6.11 (alanine) and 5.68 (serine).
• Wang and Tiwary, Enhanced polymorph metastability drives glycine nucleation in aqueous salt solutions, PNAS 2025 2025 doi:10.1073/pnas.2503490122. Alpha-glycine, the thermodynamically stable crystal phase, forms through hydrogen-bonded cyclic dimers; glycine crystallizes in more than one polymorph depending on conditions.