Nitrilotriacetic acid

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 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, formaldehyde, and sodium cyanide or hydrogen cyanide. Worldwide capacity is estimated at 100 thousand tonnes per year. NTA is also cogenerated as an impurity in the synthesis of EDTA, arising from reactions of the ammonia coproduct. Older routes to NTA included alkylation of ammonia with chloroacetic acid and oxidation of triethanolamine.

Coordination chemistry and applications
The conjugate base of NTA is a tripodal tetradentate trianionic ligand, forming coordination compounds with a variety of metal ions.

Like EDTA, its sodium salt is used for water softening to remove Ca2+. For this purpose, NTA is a replacement for triphosphate, which once was widely used in detergents, and cleansers, but can cause eutrophication of lakes.

In one application, sodium NTA removes Cr, Cu, and As from wood that had been treated with chromated copper arsenate.

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 method. The modified NTA is used to immobilize nickel 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 beads. This Ni-NTA Agarose is the most used tool to purify His-tagged proteins via affinity chromatography.

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), HON(CH2CO2H)2 (registry number = 87339-38-6) See HIDA scan.