Nitrilotriacetic acid
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 462261723
| ImageFile = Nitrilotriacetic-acid-2D-skeletal.png
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageSize = 160
| ImageName = Skeletal formula of nitrilotriacetic acid
| PIN = 2,2′,2′′-Nitrilotriacetic acid{{cite book | title=Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = The Royal Society of Chemistry | date = 2014 | location = Cambridge | pages = 21, 679 | doi = 10.1039/9781849733069 | isbn = 978-0-85404-182-4| last1 = Favre | first1 = Henri A. | last2 = Powell | first2 = Warren H. }}
| OtherNames = N,N-Bis(carboxymethyl)glycine
2-[Bis(carboxymethyl)amino]acetic acid{{cite web|title=Nitrilotriacetic Acid - Compound Summary|url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=8758&loc=ec_rcs|work=PubChem Compound|publisher=National Center for Biotechnology Information|access-date=13 July 2012|location=USA|date=26 March 2005|at=Identification}}
Triglycine[http://www.chemspider.com/8428 Nitrilotriacetic acid] Trilon
|Section1={{Chembox Identifiers
| CASNo = 139-13-9
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo_Comment = (free acid)
| CASNo2 = 5064-31-3
| CASNo2_Ref = {{cascite|correct|CAS}}
| CASNo2_Comment = (trisodium salt)
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = KA90006V9D
| UNII1_Ref = {{fdacite|correct|FDA}}
| UNII1 = E3C8R2M0XD
| UNII1_Comment = (trisodium salt)
| PubChem = 8758
| ChemSpiderID = 8428
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| EINECS = 205-355-7
| UNNumber = 2811
| DrugBank = DB03040
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| KEGG = C14695
| KEGG_Ref = {{keggcite|changed|kegg}}
| MeSHName = Nitrilotriacetic+Acid
| ChEBI = 44557
| ChEBI_Ref = {{ebicite|correct|EBI}}
| RTECS = AJ0175000
| Beilstein = 1710776
| Gmelin = 3726
| SMILES = O=C(O)CN(CC(=O)O)CC(=O)O
| StdInChI = 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)
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MGFYIUFZLHCRTH-UHFFFAOYSA-N
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
}}
|Section2={{Chembox Properties
| C=6 | H=9 | N=1 | O=6
| Solubility = Insoluble. <0.01 g/100 mL at 23°C
| Appearance = White crystals
}}
|Section3={{Chembox Thermochemistry
| DeltaHf = −1.3130–−1.3108 MJ mol−1
}}
|Section4={{Chembox Hazards
| GHSPictograms = {{gHS exclamation mark}} {{gHS health hazard}}
| GHSSignalWord = WARNING
| HPhrases = {{h-phrases|302|319|351}}
| PPhrases = {{p-phrases|281|305+351+338}}
| FlashPtC = 100
| LD50 = 1.1 g kg−1 (oral, rat)
}}
|Section5={{Chembox Related
| OtherFunction_label = alkanoic acids
| OtherFunction = {{unbulleted list|EDTA|Iminodiacetic acid|EDDS}}
| OtherCompounds = {{unbulleted list|Triethanolamine|Tris(2-aminoethyl)amine}}
}}
}}
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+.[http://www.inchem.org/documents/iarc/vol48/48-12.html Nitrilotriacetic Acid and Its Salts], International Agency for Research on Cancer
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.{{Ullmann | year=2022|doi=10.1002/14356007.a17_377.pub3 |title = Nitrilotriacetic Acid |first1= Thomas |last1=Schmidt |first2=Charalampos |last2=Gousetis |first3=Hans-Joachim |last3=Opgenorth}} NTA is also cogenerated as an impurity in the synthesis of EDTA, arising from reactions of the ammonia coproduct.{{cite journal |last1=Hart |first1=J. Roger |title=Ethylenediaminetetraacetic Acid and Related Chelating Agents |journal=Ullmann's Encyclopedia of Industrial Chemistry |date=15 June 2000 |doi=10.1002/14356007.a10_095}} 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.{{cite journal |last1=Barnett |first1=B. L. |last2=Uchtman |first2=V. A. |title=Structural investigations of calcium-binding molecules. 4. Calcium binding to aminocarboxylates. Crystal structures of Ca(CaEDTA). 7H2O and Na(CaNTA) |journal=Inorganic Chemistry |date=1 October 1979 |volume=18 |issue=10 |pages=2674–2678 |doi=10.1021/ic50200a007}}
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.{{cite journal |last1=Chang |first1=Fang-Chih |last2=Wang |first2=Ya-Nang |last3=Chen |first3=Pin-Jui |last4=Ko |first4=Chun-Han |title=Factors affecting chelating extraction of Cr, Cu, and As from CCA-treated wood |journal=Journal of Environmental Management |date=June 2013 |volume=122 |pages=42–46 |doi=10.1016/j.jenvman.2013.02.012}}
=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.{{cite journal|last1=Liu|first1=Weijing|title=Layer-by-Layer Deposition with Polymers Containing Nitrilotriacetate, A Convenient Route to Fabricate Metal- and Protein-Binding Films|journal=ACS Applied Materials & Interfaces|date=2016|volume=8|issue=16|pages=10164–73|doi=10.1021/acsami.6b00896|pmid=27042860}} 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.[http://www1.qiagen.com/literature/handbooks/PDF/Protein/Expression/QXP_QIAexpressionist/1024473_QXPHB_0603.pdf qiaexpressionist]
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.{{Cite journal|last1=Lauer|first1=Sabine A.|last2=Nolan|first2=John P.|date=2002|title=Development and characterization of Ni-NTA-bearing microspheres|journal=Cytometry|volume=48|issue=3|pages=136–145|doi=10.1002/cyto.10124|pmid=12116359|issn=1097-0320|doi-access=free}}
For laboratory uses, Ernst Hochuli et al. (1987) coupled the NTA ligand and nickel ions to agarose beads.{{Cite journal|last1=Hochuli|first1=E.|last2=Döbeli|first2=H.|last3=Schacher|first3=A.|date=January 1987|title=New metal chelate adsorbent selective for proteins and peptides containing neighbouring histidine residues|journal=Journal of Chromatography A|volume=411|pages=177–184|doi=10.1016/s0021-9673(00)93969-4|pmid=3443622|issn=0021-9673}} 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 [Ni(NTA)(H2O)2]−.
File:Calcium complex of NTA trianion.svg|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. 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.{{cite journal |last1=Brouwer |first1=N. M. |last2=Terpstra |first2=P. M. J. |title=Ecological and toxicological properties of nitrilotriacetic acid (NTA) as a detergent builder |journal=Tenside Surfactants Detergents |date=May 1995 |volume=32 |issue=3 |pages=225–228 |doi=10.1515/tsd-1995-320305}}
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), {{chem2|HON(CH2CO2H)2}} (registry number = 87339-38-6){{cite journal |doi=10.1002/ejoc.200601053 |title=Stabilizing Factors for Vanadium(IV) in Amavadin |date=2007 |last1=Hubregtse |first1=Ton |last2=Hanefeld |first2=Ulf |last3=Arends |first3=Isabel W. C. E. |journal=European Journal of Organic Chemistry |volume=2007 |issue=15 |pages=2413–2422 }} See HIDA scan.