 | |
| Names | |
|---|---|
| IUPAC name N,N′-(Ethane-1,2-diyl)bis[N-(carboxymethyl)glycine][1] | |
| Systematic IUPAC name 2,2′,2′′,2′′′-(Ethane-1,2-diyldinitrilo)tetraacetic acid[1] | |
Other names
| |
| Identifiers | |
3D model (JSmol) | |
| Abbreviations | EDTA, H4EDTA |
| 1716295 | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
|
| DrugBank |
|
| ECHA InfoCard | 100.000.409 |
| EC Number |
|
| 144943 | |
| KEGG |
|
| MeSH | Edetic+Acid |
| RTECS number |
|
| UNII |
|
| UN number | 3077 |
| |
| |
| Properties | |
| C10H16N2O8 | |
| Molar mass | 292.244 g·mol−1 |
| Appearance | Colourless crystals |
| Density | 0.860 g cm−3 (at 20 °C) |
| logP | −0.836 |
| Acidity (pKa) | 2.0, 2.7, 6.16, 10.26[2] |
| Thermochemistry | |
Std enthalpy of formation(ΔfH⦵298) | −1765.4 to −1758.0 kJ mol−1 |
Std enthalpy of combustion(ΔcH⦵298) | −4461.7 to −4454.5 kJ mol−1 |
| Pharmacology | |
| S01XA05 (WHO) V03AB03 (WHO) (salt) | |
| |
| Hazards | |
| GHS labelling: | |
 | |
| Warning | |
| H319 | |
| P305+P351+P338 | |
| NFPA 704 (fire diamond) | |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose) | 1000 mg/kg (oral, rat)[3] |
| Related compounds | |
Related alkanoic acids | |
Related compounds | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Ethylenediaminetetraacetic acid (EDTA), also calledEDTA acid, is anaminopolycarboxylic acid with the formula[CH2N(CH2CO2H)2]2. This white, slightly water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-solublecomplexes even at neutral pH. It is thus used to dissolve Fe- and Ca-containing scale as well as to deliver iron ions under conditions where its oxides are insoluble. EDTA is available as several salts, notablydisodium EDTA,sodium calcium edetate, andtetrasodium EDTA, but these all function similarly.[4]
EDTA is widely used in industry. It also has applications in food preservation, medicine, cosmetics, water softening, in laboratories, and other fields.
EDTA is mainly used tosequester (bind or confine) metal ions in aqueous solution. In thetextile industry, it prevents metal ion impurities from modifying colours of dyed products. In thepulp and paper industry, EDTA inhibits the ability of metal ions, especiallyMn2+, from catalysing thedisproportionation ofhydrogen peroxide, which is used inchlorine-free bleaching.
Aqueous [Fe(EDTA)]− is used for removing ("scrubbing")hydrogen sulfide from gas streams. This conversion is achieved by oxidising the hydrogen sulfide to elemental sulfur, which is non-volatile:
In this application, the iron(III) centre isreduced to its iron(II) derivative, which can then be reoxidised by air. In a similar manner,nitrogen oxides are removed from gas streams using[Fe(EDTA)]2−
.
In a similar manner, EDTA is added to some food as apreservative or stabiliser to prevent catalytic oxidative decolouration, which is catalysed by metal ions.[5]
The reduction of water hardness in laundry applications and the dissolution of scale in boilers both rely on EDTA and relatedcomplexants to bindCa2+,Mg2+, as well as other metal ions. Once bound to EDTA, these metal complexes are less likely to form precipitates or to interfere with the action of thesoaps anddetergents.[citation needed] For similar reasons, cleaning solutions often contain EDTA. In a similar manner EDTA is used in the cement industry for the determination of freelime and freemagnesia in cement andclinkers.[6][page needed]
Thesolvation ofFe3+ ions at or below near neutralpH can be accomplished using EDTA. This property is useful inagriculture including hydroponics. However, given the pH dependence of ligand formation, EDTA is not helpful for improving iron solubility in above neutral soils.[7] Otherwise, at near-neutral pH and above, iron(III) forms insoluble salts, which are lessbioavailable to susceptible plant species.
EDTA was used in separation of thelanthanide metals byion-exchange chromatography. Perfected by F. H. Speddinget al. in 1954, the method relies on the steady increase instability constant of the lanthanide EDTA complexes withatomic number.[8] Usingsulfonatedpolystyrene beads andCu2+ as a retaining ion, EDTA causes the lanthanides to migrate down the column of resin while separating into bands of pure lanthanides. The lanthanides elute in order of decreasing atomic number. Due to the expense of this method, relative tocountercurrent solvent extraction, ion exchange is now used only to obtain the highest purities of lanthanides (typically greater than 99.99%).[citation needed]
Sodium calcium edetate, an EDTA derivative, is used to bind metal ions in the practice ofchelation therapy, such as for treatingmercury andlead poisoning.[9] It is used in a similar manner to remove excessiron from the body. This therapy is used to treat the complication of repeatedblood transfusions, as would be applied to treatthalassaemia.
Inmedical diagnosis and organ function tests (here,kidney function test), thechromium(III) complex [Cr(EDTA)]− (as radioactivechromium-51 (51Cr)) is administeredintravenously and its filtration into theurine is monitored. This method is useful for evaluatingglomerular filtration rate (GFR) innuclear medicine.[10]
EDTA is used extensively in the analysis of blood. It is ananticoagulant for blood samples forCBC/FBCs, where the EDTA chelates the calcium present in the blood specimen, arresting the coagulation process and preserving blood cell morphology.[11] Tubes containing EDTA are marked withlavender (purple) or pink tops.[12] EDTA is also in tan top tubes for lead testing and can be used in royal blue top tubes for trace metal testing.[12]
EDTA is a slime dispersant, and has been found to be highly effective in reducing bacterial growth during implantation ofintraocular lenses (IOLs).[13]
Dentists andendodontists use EDTA solutions to remove inorganic debris (smear layer) and lubricate theroot canals in endodontics. This procedure helps prepare root canals forobturation. Furthermore, EDTA solutions with the addition of asurfactant loosen upcalcifications inside a root canal and allow instrumentation (canal shaping) and facilitate apical advancement of a file in a tight or calcified root canal towards the apex.
It serves as apreservative (usually to enhance the action of another preservative such asbenzalkonium chloride orthiomersal) in ocular preparations andeyedrops.
Somealternative practitioners believe EDTA acts as anantioxidant, preventingfree radicals from injuringblood vessel walls, therefore reducingatherosclerosis.[14] These ideas are unsupported by scientific studies, and seem to contradict some currently accepted principles.[15] TheU.S. FDA has not approved it for the treatment of atherosclerosis.[16]
Inshampoos, cleaners, and other personal care products, EDTA salts are used as a sequestering agent to improve their stability in air.[17]
In the laboratory, EDTA is widely used for scavenging metal ions: Inbiochemistry andmolecular biology, ion depletion is commonly used to deactivatemetal-dependent enzymes, either as an assay for their reactivity or to suppress damage toDNA,proteins, andpolysaccharides.[18] EDTA also acts as a selectiveinhibitor against dNTP hydrolyzing enzymes (Taq polymerase,dUTPase, MutT),[19] liverarginase[20] andhorseradish peroxidase[21] independently of metal ionchelation. These findings urge the rethinking of the utilisation of EDTA as a biochemically inactive metal ion scavenger in enzymatic experiments. In analytical chemistry, EDTA is used incomplexometric titrations and analysis ofwater hardness or as amasking agent to sequester metal ions that would interfere with the analyses.
EDTA finds many specialised uses in the biomedical labs, such as inveterinaryophthalmology as ananticollagenase to prevent the worsening ofcorneal ulcers in animals. Intissue culture, EDTA is used as a chelating agent that binds tocalcium and prevents joining ofcadherins between cells, preventing clumping of cells grown in liquid suspension, or detaching adherent cells forpassaging. Inhistopathology, EDTA can be used as a decalcifying agent making it possible to cut sections using amicrotome once the tissue sample is demineralised.
EDTA is also known to inhibit a range ofmetallopeptidases, the method of inhibition occurs via thechelation of the metal ion required for catalytic activity.[22] EDTA can also be used to test forbioavailability of heavy metals insediments. However, it mayinfluence the bioavailability of metals in solution, which may pose concerns regarding its effects in the environment, especially given its widespread uses and applications.
The oxidising properties of [Fe(EDTA)]− are used inphotography to solubilisesilver particles.[4]
EDTA is also used to remove crud (corroded metals) from fuel rods in nuclear reactors.[23]
EDTA exhibits low acute toxicity withLD50 (rat) of 2.0 g/kg to 2.2 g/kg.[4] It has been found to be bothcytotoxic and weaklygenotoxic in laboratory animals. Oral exposures have been noted to cause reproductive and developmental effects.[17] The same study[17] also found that both dermal exposure to EDTA in most cosmetic formulations and inhalation exposure to EDTA inaerosolised cosmetic formulations would produce exposure levels below those seen to be toxic in oral dosing studies.
The compound was first described in 1935 byFerdinand Münz,[24] who prepared the compound fromethylenediamine andchloroacetic acid.[25] Today, EDTA is mainly synthesised fromethylenediamine (1,2-diaminoethane),formaldehyde, andsodium cyanide.[26] This route yields the tetrasodium EDTA, which is converted in a subsequent step into the acid forms:
This process is used to produce about 80,000 tonnes of EDTA each year. Impurities cogenerated by this route includeglycine andnitrilotriacetic acid; they arise from reactions of theammonia coproduct.[4]
To describe EDTA and its variousprotonated forms, chemists distinguish betweenEDTA4−
, theconjugate base that is theligand, and H4EDTA, theprecursor to that ligand. At very low pH (very acidic conditions) the fully protonated H6EDTA2+ form predominates, whereas at very high pH or very basic condition, the fully deprotonatedEDTA4−
form is prevalent. In this article, the term EDTA is used to mean H4−xEDTAx−, whereas in its complexesEDTA4−
stands for the tetraanion ligand.
Incoordination chemistry,EDTA4−
is a member of theaminopolycarboxylic acid family of ligands.EDTA4−
usually binds to a metal cation through its two amines and four carboxylates, i.e., it is ahexadentate ("six-toothed")chelating agent. Many of the resultingcoordination compounds adoptoctahedral geometry. Although of little consequence for its applications, these octahedral complexes arechiral. Thecobalt(III) anion [Co(EDTA)]− has been resolved intoenantiomers.[28] Many complexes ofEDTA4−
adopt more complex structures due to either the formation of an additional bond to water,i.e. seven-coordinate complexes, or the displacement of one carboxylate arm by water. Theiron(III)complex of EDTA is seven-coordinate.[29] Early work on the development of EDTA was undertaken byGerold Schwarzenbach in the 1940s.[30] EDTA forms especially strong complexes withMn(II),Cu(II), Fe(III),Pb(II) and Co(III).[31][page needed]
Several features of EDTA's complexes are relevant to its applications. First, because of its highdenticity, this ligand has a high affinity for metal cations:
Written in this way, theequilibrium quotient shows that metal ions compete with protons for binding to EDTA. Because metal ions are extensively enveloped by EDTA, theircatalytic properties are often suppressed. Finally, since complexes ofEDTA4−
areanionic, they tend to be highly soluble in water. For this reason, EDTA is able to dissolve deposits ofmetal oxides andcarbonates.
ThepKa values of free EDTA are 0, 1.5, 2, 2.66 (deprotonation of the fourcarboxyl groups) and 6.16, 10.24 (deprotonation of the twoamino groups).[32]
EDTA is in such widespread use that questions have been raised whether it is apersistent organic pollutant. While EDTA serves many positive functions in different industrial, pharmaceutical and other avenues, the longevity of EDTA can pose serious issues in the environment. The degradation of EDTA is slow. It mainly occursabiotically in the presence of sunlight.[33]
The most important process for the elimination of EDTA from surface waters is directphotolysis at wavelengths below 400 nm.[34] Depending on the light conditions, the photolysishalf-lives of iron(III) EDTA in surface waters can range from as low as 11.3 minutes up to more than 100 hours.[35] Degradation of FeEDTA, but not EDTA itself, produces iron complexes of the triacetate (ED3A), diacetate (EDDA), and monoacetate (EDMA) – 92% of EDDA and EDMA biodegrades in 20 hours while ED3A displays significantly higher resistance. Many environmentally-abundant EDTA species (such asMg2+ andCa2+) are more persistent.
Inindustrial wastewater treatment plants, EDTA can be degraded at about 80% usingmicroorganisms.[36] Resulting byproducts areethylenediaminetriacetic acid andiminodiacetic acid (IDA) – suggesting that both the backbone and acetyl groups were attacked. Some microorganisms have even been discovered to form nitrates out of EDTA, but they function optimally at moderately alkaline conditions of pH 9.0–9.5.[37]
Several bacterial strains isolated from sewage treatment plants efficiently degrade EDTA. Specific strains includeAgrobacterium radiobacter ATCC 55002[38] and the sub-branches ofPseudomonadota like BNC1, BNC2,[39] and strain DSM 9103.[40] The three strains share similar properties ofaerobic respiration and are classified asgram-negative bacteria. Unlike photolysis, the chelated species is not exclusive to iron(III) in order to be degraded. Rather, each strain uniquely consumes varying metal–EDTA complexes through several enzymatic pathways. Agrobacterium radiobacter only degrades Fe(III) EDTA[39] while BNC1 and DSM 9103 are not capable of degrading iron(III) EDTA and are more suited forcalcium,barium,magnesium andmanganese(II) complexes.[41] EDTA complexes require dissociation before degradation.
Interest in environmental safety has raised concerns about biodegradability ofaminopolycarboxylates such as EDTA. These concerns incentivize the investigation of alternative aminopolycarboxylates.[33] Candidate chelating agents includenitrilotriacetic acid (NTA), iminodisuccinic acid (IDS),polyaspartic acid,S,S-ethylenediamine-N,N′-disuccinic acid (EDDS), methylglycinediacetic acid (MGDA), andL-Glutamic acidN,N-diacetic acid, tetrasodium salt (GLDA).[42]
Commercially used since 1998,iminodisuccinic acid (IDS) biodegrades by about 80% after only 7 days. IDS binds to calcium exceptionally well and forms stable compounds with other heavy metal ions. In addition to having a lower toxicity after chelation, IDS is degraded byAgrobacterium tumefaciens (BY6), which can be harvested on a large scale. The enzymes involved,IDS epimerase and C−Nlyase, do not require anycofactors.[43]
Polyaspartic acid, like IDS, binds to calcium and other heavy metal ions. It has many practical applications including corrosion inhibitors, wastewater additives, and agricultural polymers. A polyaspartic acid-basedlaundry detergent was the first laundry detergent in the world to receive theEU flower ecolabel.[44] Calcium binding ability of polyaspartic acid has been exploited for targeting of drug-loaded nanocarriers to bone.[45] Preparation ofhydrogels based on polyaspartic acid, in a variety of physical forms ranging fromfiber toparticle, can potentially enable facile separation of the chelated ions from a solution.[46] Therefore, despite being weaker than EDTA, polyaspartic acid can still be regarded as a viable alternative due to these features as well asbiocompatibility andbiodegradability.[47]
Astructural isomer of EDTA,ethylenediamine-N,N′-disuccinic acid (EDDS) is readily biodegradable at high rate in itsS,S form.[48]
Trisodium dicarboxymethyl alaninate, also known as methylglycinediacetic acid (MGDA), has a high rate of biodegradation at over 68%, but unlike many other chelating agents can degrade without the assistance of adapted bacteria. Additionally, unlike EDDS or IDS, MGDA can withstand higher temperatures while maintaining a high stability as well as the entire pH range.[citation needed] MGDA has been shown to be an effective chelating agent, with a capacity for mobilization comparable with that ofnitrilotriacetic acid (NTA), with application to water for industrial use and for the removal ofcalcium oxalate from urine from patients withkidney stones.[49]
The most sensitive method of detecting and measuring EDTA in biological samples is selected reaction monitoringcapillary electrophoresismass spectrometry (SRM-CE/MS), which has adetection limit of 7.3 ng/mL in human plasma and aquantitation limit of 15 ng/mL.[50] This method works with sample volumes as small as 7–8 nL.[50]
EDTA has also been measured in non-alcoholic beverages usinghigh performance liquid chromatography (HPLC) at a level of 2.0 μg/mL.[51][52]
In the movieBlade (1998), EDTA is used as a weapon to kill vampires, exploding when in contact with vampire blood.[53]
Blood on the sock that was used as evidence againstO. J. Simpson, in thekilling of Nicole Brown Simpson and Ronald Goldman, had high levels of EDTA, according to defense attorneys.[54]
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