Nitrilotriacetic acid

Nitrilotriacetic acid
Names
	Preferred IUPAC name 2,2′,2′′-Nitrilotriacetic acid
	Other names N,N-Bis(carboxymethyl)glycine; 2-[Bis(carboxymethyl)amino]acetic acid; Triglycine Trilon
Identifiers
CAS Number	139-13-9 (free acid) ; 5064-31-3 (trisodium salt) ;
3D model (JSmol)	Interactive image;
Beilstein Reference	1710776
ChEBI	CHEBI:44557 ;
ChemSpider	8428 ;
DrugBank	DB03040 ;
ECHA InfoCard	100.004.869
EC Number	205-355-7;
Gmelin Reference	3726
KEGG	C14695 ;
MeSH	Nitrilotriacetic+Acid
PubChem CID	8758;
RTECS number	AJ0175000;
UNII	KA90006V9D ; E3C8R2M0XD (trisodium salt) ;
UN number	2811
CompTox Dashboard (EPA)	DTXSID6020939 ;
	InChI InChI=1S/C6H9NO6/c8-4(9)1-7(2-5(10)11)3-6(12)13/h1-3H2,(H,8,9)(H,10,11)(H,12,13) Key: MGFYIUFZLHCRTH-UHFFFAOYSA-N ;
	SMILES O=C(O)CN(CC(=O)O)CC(=O)O;
Properties
Chemical formula	C6H9NO6
Molar mass	191.14
Appearance	White crystals
Melting point	246 °C (475 °F; 519 K)
Solubility in water	Insoluble. <0.01 g/100 mL at 23°C
Thermochemistry
Std enthalpy of; formation (ΔfH⦵298)	−1.3130–−1.3108 MJ mol−1
Hazards
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H302, H319, H351
Precautionary statements	P281, P305+P351+P338
Flash point	100 °C (212 °F; 373 K)
	Lethal dose or concentration (LD, LC):
LD50 (median dose)	1.1 g kg−1 (oral, rat)
Related compounds
Related alkanoic acids	EDTA; Iminodiacetic acid; EDDS;
Related compounds	Triethanolamine; Tris(2-aminoethyl)amine;
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

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⁺.^[5]

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.^[6] NTA is also cogenerated as an impurity in the synthesis of EDTA, arising from reactions of the ammonia coproduct.^[7] 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.^[8]

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.^[9]

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.^[10] 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.^[11]

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.^[12]

For laboratory uses, Ernst Hochuli et al. (1987) coupled the NTA ligand and nickel ions to agarose beads.^[13] This Ni-NTA Agarose is the most used tool to purify His-tagged proteins via affinity chromatography.

NTA complexes
Three views of the structure of [Ni(NTA)(H₂O)₂]⁻.
Structure of the nitrilotriacetate anion [Ca(NTA)(H₂O)₃]⁻.

Toxicity and environment

In contrast to EDTA, NTA is easily biodegradable and is almost completely removed during wastewater treatment.^[6] 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.^[14]

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)^[15] See HIDA scan.

References

^ "Nitrilotriacetic Acid - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 26 March 2005. Identification. Retrieved 13 July 2012.
^ Nitrilotriacetic acid
^ Favre, Henri A.; Powell, Warren H. (2014). Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. pp. 21, 679. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.
^ ^a ^b ^c ChemBK Chemical Database http://www.chembk.com/en/chem/Nitrilotriacetic%20acid
^ Nitrilotriacetic Acid and Its Salts, International Agency for Research on Cancer
^ ^a ^b Thomas Schmidt, Charalampos Gousetis, Hans-Joachim Opgenorth (2022). "Nitrilotriacetic Acid". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a17_377.pub3. ISBN 978-3527306732.{{cite encyclopedia}}: CS1 maint: multiple names: authors list (link)
^ Hart, J. Roger (2005) "Ethylenediaminetetraacetic Acid and Related Chelating Agents" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim. doi:10.1002/14356007.a10_095
^ B. L. Barnett, V. A. Uchtman (1979). "Structural Investigations of Calcium-Binding Molecules. 4. Calcium Binding to Aminocarboxylates. Crystal Structures of Ca(CaEDTA)^.7H₂O and Na(CaNTA)". Inorg. Chem. 18 (10): 2674–2678. doi:10.1021/ic50200a007.
^ Fang-Chih, C.; Ya-Nang, W.; Pin-Jui, C.; Chun-Han, K. Factors affecting chelating extraction of Cr, Cu, and As from CCA-treated wood. J. Environ. Manag. 2013, 122.
^ Liu, Weijing (2016). "Layer-by-Layer Deposition with Polymers Containing Nitrilotriacetate, A Convenient Route to Fabricate Metal- and Protein-Binding Films". ACS Applied Materials & Interfaces. 8 (16): 10164–73. doi:10.1021/acsami.6b00896. PMID 27042860.
^ qiaexpressionist
^ Lauer, Sabine A.; Nolan, John P. (2002). "Development and characterization of Ni-NTA-bearing microspheres". Cytometry. 48 (3): 136–145. doi:10.1002/cyto.10124. ISSN 1097-0320. PMID 12116359.
^ Hochuli, E.; Döbeli, H.; Schacher, A. (January 1987). "New metal chelate adsorbent selective for proteins and peptides containing neighbouring histidine residues". Journal of Chromatography A. 411: 177–184. doi:10.1016/s0021-9673(00)93969-4. ISSN 0021-9673. PMID 3443622.
^ Brouwer, N.; Terpstra, P. Ecological and Toxicological Properties of Nitrilotriacetic Acid (NTA) as a Detergent Builder. Tenside Surfactants Detergents 1995, 32, 225-228.
^ Hubregtse, Ton; Hanefeld, Ulf; Arends, Isabel W. C. E. (2007). "Stabilizing Factors for Vanadium(IV) in Amavadin". European Journal of Organic Chemistry. 2007 (15): 2413–2422. doi:10.1002/ejoc.200601053.

[pc1-1] "Nitrilotriacetic Acid - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 26 March 2005. Identification. Retrieved 13 July 2012.

[2] Nitrilotriacetic acid

[iupac2013-3] Favre, Henri A.; Powell, Warren H. (2014). Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. pp. 21, 679. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.

[ChemBK-4] ChemBK Chemical Database http://www.chembk.com/en/chem/Nitrilotriacetic%20acid

[5] Nitrilotriacetic Acid and Its Salts, International Agency for Research on Cancer

[Ullmann-6] Thomas Schmidt, Charalampos Gousetis, Hans-Joachim Opgenorth (2022). "Nitrilotriacetic Acid". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a17_377.pub3. ISBN 978-3527306732.{{cite encyclopedia}}: CS1 maint: multiple names: authors list (link)

[Ullmann/Roger-7] Hart, J. Roger (2005) "Ethylenediaminetetraacetic Acid and Related Chelating Agents" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim. doi:10.1002/14356007.a10_095

[8] B. L. Barnett, V. A. Uchtman (1979). "Structural Investigations of Calcium-Binding Molecules. 4. Calcium Binding to Aminocarboxylates. Crystal Structures of Ca(CaEDTA)^.7H₂O and Na(CaNTA)". Inorg. Chem. 18 (10): 2674–2678. doi:10.1021/ic50200a007.

[9] Fang-Chih, C.; Ya-Nang, W.; Pin-Jui, C.; Chun-Han, K. Factors affecting chelating extraction of Cr, Cu, and As from CCA-treated wood. J. Environ. Manag. 2013, 122.

[10] Liu, Weijing (2016). "Layer-by-Layer Deposition with Polymers Containing Nitrilotriacetate, A Convenient Route to Fabricate Metal- and Protein-Binding Films". ACS Applied Materials & Interfaces. 8 (16): 10164–73. doi:10.1021/acsami.6b00896. PMID 27042860.

[11] qiaexpressionist

[12] Lauer, Sabine A.; Nolan, John P. (2002). "Development and characterization of Ni-NTA-bearing microspheres". Cytometry. 48 (3): 136–145. doi:10.1002/cyto.10124. ISSN 1097-0320. PMID 12116359.

[13] Hochuli, E.; Döbeli, H.; Schacher, A. (January 1987). "New metal chelate adsorbent selective for proteins and peptides containing neighbouring histidine residues". Journal of Chromatography A. 411: 177–184. doi:10.1016/s0021-9673(00)93969-4. ISSN 0021-9673. PMID 3443622.

[14] Brouwer, N.; Terpstra, P. Ecological and Toxicological Properties of Nitrilotriacetic Acid (NTA) as a Detergent Builder. Tenside Surfactants Detergents 1995, 32, 225-228.

[15] Hubregtse, Ton; Hanefeld, Ulf; Arends, Isabel W. C. E. (2007). "Stabilizing Factors for Vanadium(IV) in Amavadin". European Journal of Organic Chemistry. 2007 (15): 2413–2422. doi:10.1002/ejoc.200601053.

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