Nitrilotriacetic acid (NTA) is the aminopolycarboxylic acid with the formula N(CH₂CO₂H)₃. It is a colourless solid. Its conjugate base nitrilotriacetate is used as a

chelating agent Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

for Ca²⁺, Co²⁺, Cu²⁺, and Fe³⁺.

Production and use

Nitrilotriacetic acid is commercially available as the free acid and as the sodium salt. It is produced from

ammonia Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...

formaldehyde Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...

, and

sodium cyanide Sodium cyanide is a compound with the formula Na C N and the structure . It is a white, water-soluble solid. Cyanide has a high affinity for metals, which leads to the high toxicity of this salt. Its main application, in gold mining, also expl ...

hydrogen cyanide Hydrogen cyanide (formerly known as prussic acid) is a chemical compound with the chemical formula, formula HCN and structural formula . It is a highly toxic and flammable liquid that boiling, boils slightly above room temperature, at . HCN is ...

. NTA is also cogenerated as an impurity in the synthesis of

EDTA Ethylenediaminetetraacetic acid (EDTA), also called EDTA acid, is an aminopolycarboxylic acid with the formula . This white, slightly water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-solubl ...

, arising from reactions of the ammonia coproduct. Older routes to NTA included alkylation of ammonia with chloroacetic acid and oxidation of

triethanolamine Triethanolamine, or TEOA, is an organic compound with the chemical formula . It is a colourless, viscous liquid. It is both a tertiary amine and a triol. A triol is a molecule with three alcohol groups. Approximately 150,000 tonnes were produ ...

Coordination chemistry and applications

The conjugate base of NTA is a tripodal tetradentate trianionic ligand, forming

coordination compound A coordination complex is a chemical compound consisting of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of chemical bond, bound molecules or ions, that are in turn known as ' ...

s with a variety of metal ions. Like

, its sodium salt is used for

water softening Water softening is the removal of calcium, magnesium, and certain other metal cations in hard water. The resulting soft water requires less soap for the same cleaning effort, as soap is not wasted bonding with calcium ions. Soft water also extend ...

to remove Ca²⁺. For this purpose, NTA is a replacement for

triphosphate A polyphosphate is a salt or ester of polymeric oxyanions formed from tetrahedral PO4 (phosphate) structural units linked together by sharing oxygen atoms. Polyphosphates can adopt linear or a cyclic (also called, ring) structures. In biology, th ...

, which once was widely used in detergents, and cleansers, but can cause

eutrophication Eutrophication is a general term describing a process in which nutrients accumulate in a body of water, resulting in an increased growth of organisms that may deplete the oxygen in the water; ie. the process of too many plants growing on the s ...

of lakes. In one application, sodium NTA removes Cr, Cu, and As from wood that had been treated with

chromated copper arsenate Chromated copper arsenate (CCA) is a wood preservative containing compounds of chromium, copper, and arsenic, in various proportions. It is used to impregnate timber and other wood products, especially those intended for outdoor use, in order to pr ...

Laboratory uses

In the laboratory, this compound is used in complexometric titrations. A variant of NTA is used for protein isolation and purification in the

His-tag A polyhistidine-tag, best known by the trademarked name His-tag, is an amino acid motif in proteins that typically consists of at least six histidine (''His'') residues, often at the N- or C-terminus of the protein. It is also known as a hexa hi ...

method. The modified NTA is used to immobilize

nickel Nickel is a chemical element; it has symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive, but large pieces are slo ...

on a solid support. This allows purification of proteins containing a tag consisting of six histidine residues at either terminus. The His-tag binds the metal of metal chelator complexes. Previously, iminodiacetic acid was used for that purpose. Now, nitrilotriacetic acid is more commonly used. For laboratory uses, Ernst Hochuli et al. (1987) coupled the NTA ligand and nickel ions to

agarose Agarose is a heteropolysaccharide, generally extracted from certain red algae. It is a linear polymer made up of the repeating unit of agarobiose, which is a disaccharide made up of D-galactose and 3,6-anhydro-L-galactopyranose. Agarose is on ...

beads. This Ni-NTA Agarose is the most used tool to purify His-tagged proteins via affinity chromatography. Ni(NTA)(aq)23views.png, Three views of the structure of i(NTA)(H₂O)₂sup>−. File:Calcium complex of NTA trianion.svg, Structure of the nitrilotriacetate anion a(NTA)(H₂O)₃sup>−.

Toxicity and environment

In contrast to EDTA, NTA is easily biodegradable and is almost completely removed during wastewater treatment. The environmental impacts of NTA are minimal. Despite widespread use in cleaning products, the concentration in the water supply is too low to have a sizeable impact on human health or environmental quality.

Related compounds

* N-Methyliminodiacetic acid (MIDA), the N-methyl derivative of IDA * Imidodiacetic acid, the amino diacetic acid * N-(2-Carboxyethyl)iminodiacetic acid, a more biodegradable analogue of NTA * N-hydroxyiminodiacetic acid (HIDA), ( registry number = 87339-38-6) See HIDA scan.

References

{{Authority control Amines Acetic acids Chelating agents IARC Group 2B carcinogens Tripodal ligands