Nitrilotriacetic acid (NTA) is the

aminopolycarboxylic acid left, 120px, a metal complex with the EDTA anion 120px, Aspartic acid is an aminodicarboxylic acid and precursor to other ligands. An aminopolycarboxylic acid (sometimes abbreviated APCA) is a chemical compound containing one or more nitrogen at ...

with the formula N(CH₂CO₂H)₃. It is a colourless solid that is used as a

chelating agent Chelation is a type of bonding of ions and 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 ligands are ...

, which forms

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

s with metal ions (chelates) such as 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 compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...

formaldehyde Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...

, and

sodium cyanide Sodium cyanide is a poisonous compound with the formula Na C N. 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 exploits its hi ...

hydrogen cyanide Hydrogen cyanide, sometimes called prussic acid, is a chemical compound with the formula HCN and structure . It is a colorless, extremely poisonous, and flammable liquid that boils slightly above room temperature, at . HCN is produced on an ...

. Worldwide capacity is estimated at 100 thousand tonnes per year. NTA is also cogenerated as an impurity in the synthesis of

EDTA Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes eve ...

, arising from reactions of the ammonia coproduct.Hart, J. Roger (2005) "Ethylenediaminetetraacetic Acid and Related Chelating Agents" in ''Ullmann's Encyclopedia of Industrial Chemistry'', Wiley-VCH, Weinheim. Older routes to NTA included alkylation of ammonia with chloroacetic acid and oxidation of

triethanolamine Triethanolamine, or TEA is a viscous organic compound that is both a tertiary amine and a triol. A triol is a molecule with three alcohol groups. Approximately 150,000 tonnes were produced in 1999. It is a colourless compound although samples m ...

Coordination chemistry and applications

NTA is a tripodal

tetradentate In chemistry, tetradentate ligands are ligands that bind four donor atoms to a central atom to form a coordination complex. This number of donor atoms that bind is called denticity and is a method of classifying ligands. Tetradentate ligands ar ...

trianionic ligand. The uses of NTA are similar to those of EDTA, both being chelating agents. It 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 exten ...

and as a replacement to sodium and potassium

triphosphate Polyphosphates are salts or esters of polymeric oxyanions formed from tetrahedral PO4 (phosphate) structural units linked together by sharing oxygen atoms. Polyphosphates can adopt linear or a cyclic ring structures. In biology, the polyphosphate e ...

in detergents, and cleansers. In one application, NTA as a chelating agent 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 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 hexa histidine-tag, 6xHis-tag, His6 tag, by the US trad ...

method. The modified NTA is used to immobilize

nickel Nickel is a chemical element with 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 slow to ...

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 Chelation is a type of bonding of ions and 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 ligands are ...

complexes. Previously,

iminodiacetic acid Iminodiacetic acid is the organic compound with the formula HN(CH2CO2H)2, often abbreviated to IDA. A white solid, the compound is a dicarboxylic acid amine (the nitrogen atom forms a secondary amino group, not an imino group as the name suggests ...

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 seaweed. 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 ...

beads. Thi
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

Nitriloacetic acid can cause eye, skin, and respiratory tract irritation; and can cause kidney and bladder damage. The compound is anticipated to have the potential to cause human cancers. 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.Brouwer, N.; Terpstra, P. Ecological and Toxicological Properties of Nitrilotriacetic Acid (NTA) as a Detergent Builder. Tenside Surfactants Detergents 1995, 32, 225-228.

References

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