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Iodoacetic acid: Difference between revisions

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Revision as of 09:56, 24 February 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,071 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: ChEMBL.← Previous edit Latest revision as of 15:41, 11 August 2024 edit undoShyamal (talk | contribs)Autopatrolled, Administrators98,716 editsNo edit summaryTag: Visual edit 
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{{jargon|date=April 2024}}
{{chembox {{chembox
| Verifiedfields = changed
| verifiedrevid = 396496039
| ImageFile = Iodoacetic-acid-2D-skeletal.png | verifiedrevid = 415664778
| ImageFile = Iodoacetic-acid-2D-skeletal.png
| ImageSize = 150px | ImageSize = 150px
| ImageName = Skeletal formula | ImageName = Skeletal formula
| ImageFile1 = Iodoacetic-acid-3D-vdW.png | ImageFile1 = Iodoacetic-acid-3D-vdW.png
| ImageSize1 = 160px | ImageSize1 = 160px
| ImageName1 = Space-filling model | ImageName1 = Space-filling model
| ImageCaption1 = {{legend|rgb(64, 64, 64)|], C}}{{legend|white|]}}{{legend|red|], O}}{{legend|rgb(128, 0, 128)|], I}}
⚫ | OtherNames =
| PIN = Iodoacetic acid
⚫ | OtherNames = 2-Iodoacetic acid
|Section1={{Chembox Identifiers |Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5050 | ChemSpiderID = 5050
| InChI = 1/C2H3IO2/c3-1-2(4)5/h1H2,(H,4,5) | InChI = 1/C2H3IO2/c3-1-2(4)5/h1H2,(H,4,5)
| InChIKey = JDNTWHVOXJZDSN-UHFFFAOYAA | InChIKey = JDNTWHVOXJZDSN-UHFFFAOYAA
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 376280 | ChEMBL = 376280
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
Line 19: Line 24:
| StdInChIKey = JDNTWHVOXJZDSN-UHFFFAOYSA-N | StdInChIKey = JDNTWHVOXJZDSN-UHFFFAOYSA-N
| CASNo= 64-69-7 | CASNo= 64-69-7
| CASNo_Ref = {{cascite|correct|CAS}} | CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
⚫ | PubChem= 5240
| UNII = WF5188V710
⚫ | SMILES=C(C(=O)O)I
⚫ | PubChem= 5240
⚫ }}
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 74571
⚫ | SMILES=C(C(=O)O)I
⚫ }}
|Section2={{Chembox Properties |Section2={{Chembox Properties
| Formula = {{chem2|ICH2CO2H}}
| C = 2 | H = 3 | I = 1 | O = 2 | C=2|H=3|I=1|O=2
| Appearance=
| Density= | Appearance=
| MeltingPtC=81 | Density=
| MeltingPtC=81
| BoilingPtC=208 | BoilingPtC=208
| pKa = 3.12<ref>{{cite journal |last1=Dippy |first1=J. F. J. |last2=Hughes |first2=S. R. C. |last3=Rozanski |first3=A. |title=The dissociation constants of some symmetrically disubstituted succinic acids |journal=Journal of the Chemical Society |date=1959 |pages=2492–2498|doi=10.1039/jr9590002492 }}</ref>
| Solubility= | Solubility=
}} }}
|Section3={{Chembox Hazards |Section7={{Chembox Hazards
| ExternalMSDS = | ExternalSDS =
| EUClass = Toxic (T); Corrosive (C)
| GHSPictograms = {{GHS06}}{{GHS05}}
⚫ | FlashPt=
| GHSSignalWord = danger
| Autoignition=
| HPhrases = {{HPhrases|H301|H314}}
⚫ }}
| PPhrases = {{PPhrases|P280|P260|P301+P310+P330|P331|P303+P361+P353|P305+P351+P338|P310}}
| GHS_ref = <ref>GHS: </ref>
⚫ | FlashPt=
| AutoignitionPt =
⚫ }}
| Section8 = {{Chembox Related
| OtherCompounds = {{ubl|]|]|]|]|]]|]}}
}}
}} }}
'''Iodoacetic acid''' is a derivative of ]. It is a toxic compound, because, like many alkyl halides, it is an ]. It reacts with ] residues in proteins. It is often used to modify ]-groups to prevent the re-formation of ]s after the reduction of ] residues to cysteine during ] sequencing. '''Iodoacetic acid''' is an ] with the ] {{chem2|ICH2CO2H|auto=1}}. It is a derivative of ]. It is a toxic compound, because, like many ]s, it is an ].


It reacts with ] residues in ]. It is often used to modify ] to prevent the re-formation of ]s after the reduction of ] residues to cysteine during ].
⚫ ==Peptidase inhibitor==

⚫ Iodoacetate is an irreversible inhibitor of all ], with the mechanism of inhibition occurring from alkylation of the catalytic cysteine residue (see schematic). In comparison with its amide derivative, ], iodoacetate reacts substantially faster. This observation appears contradictory to standard chemical reactivity, however the presence of a favourable interaction between the positive imidazolium ion of the catalytic histidine and the negatively charged carboxyl-group of the iodoacetate is the reason for the increased activity of iodoacetate<ref>{{cite journal|doi=10.1111/j.1432-1033.1979.tb13196.x|author=Polgar, L|title=Deuterium isotope effects on papain acylation. Evidence for lack of general base catalysis and for enzyme-leaving group. interaction|journal=Eur. J. Biochem. |volume=98|issue=2 |pages=369–374 |year=1979|pmid=488108}}</ref>.]{{clear-left}}
In 1929, Dr. ] (1899-1968) discovered that ] ] ] with iodoacetic acid is unable to produce ] as ] from muscle ] is blocked, causing the muscle to result in an electrically silent contracture.<ref>{{Cite journal |last1=Shorr |first1=E. |last2=Barker |first2=S. B. |last3=Malam |first3=M. |date=1938-02-18 |title=The Influence of Iodoacetic Acid on the Respiratory Metabolism of Mammalian Tissues |url=https://www.science.org/doi/10.1126/science.87.2251.168 |journal=Science |language=en |volume=87 |issue=2251 |pages=168–169 |doi=10.1126/science.87.2251.168 |pmid=17740354 |bibcode=1938Sci....87..168S |issn=0036-8075}}</ref><ref>Lundsgaard, E., Biochem. Z., 217,162 (1930).</ref>{{cln|reason=What da hell is "electrically silent contracture"??? Please someone clear this jargon for an average mortal human being!|date=April 2024}} It was remembering this discovery, that lead ] in 1951, to speculate that one of his patients that had electromyographically silent muscle contractures brought on by high-intensity aerobic activity and anaerobic activity must have a defective muscle glycogen mechanism.<ref>{{Cite journal |last=Layzer |first=Robert B. |date=1985-02-07 |title=McArdle's Disease in the 1980s |url=http://www.nejm.org/doi/abs/10.1056/NEJM198502073120609 |journal=New England Journal of Medicine |language=en |volume=312 |issue=6 |pages=370–371 |doi=10.1056/NEJM198502073120609 |pmid=3855500 |issn=0028-4793}}</ref>

⚫ ==]==
⚫ Iodoacetate is an irreversible inhibitor of all ], with the mechanism of inhibition occurring from alkylation of the ] ] residue (see schematic). In comparison with its amide derivative, ], iodoacetate reacts substantially slower. This observation appears contradictory to standard chemical reactivity, however the presence of a favourable interaction between the positive imidazolium ion of the catalytic histidine and the negatively charged carboxyl-group of the iodoacetic acid is the reason for the increased activity of iodoacetamide.<ref>{{cite journal | author = Polgár, L. | title = Deuterium isotope effects on papain acylation. Evidence for lack of general base catalysis and for enzyme-leaving group interaction | journal = European Journal of Biochemistry | year = 1979 | volume = 98 | issue = 2 | pages = 369–374 | doi = 10.1111/j.1432-1033.1979.tb13196.x | pmid = 488108 | doi-access = free}}</ref>]s with iodoacetate.]]{{clear left}}


== Possible cancer therapy == == Possible cancer therapy ==
Several studies have shown iodoacetate has anti-tumor effects. In 2002 Dr. ] showed that "a single IAA treatment of tumor-bearing mice significantly increased the levels of plasma lactate dehydrogenase (LDH) activity, while it also significantly decreased the levels of plasma glucose and liver total protein, RNA and DNA, compared to normal controls."<ref>{{cite journal |author=Fawzia A Fahim, Amr Y Esmat, Essam A Mady and Emad K Ibrahim |title=Antitumor Activities of Iodoacetate and Dimethylsulphoxide Against Solid Ehrlich Carcinoma Growth in Mice |journal=Biol. Res.|volume=36 |issue=2 |pages=253–262 |year=2003 |pmid=14513720 }}</ref> In 1975 Melvin S. Rhein, Joyce A. Filppi and Victor S. Moore showed that iodoacetate improved the immune response of bone marrow.<ref>{{cite journal |author=Melvin S. Rhein, Joyce A. Filppi and Victor S. Moore |title=Effect of Iodoacetate on the Bone Marrow Immunocompetence of AKR Mice.|journal=Cancer Research|volume=35 |pages=1514–1519 |year=1975 |pmid=1093673 |issue=6 }}</ref> In 1966 Charles A. Apffel, Barry G. Arnason & John H. Peters showed anti-tumor activity for iodoacetate.<ref>{{cite journal |author=Charles A. Apffel, Barry G. Arnason & John H. Peters |title=Induction of tumour immunity with tumour cells treated with iodoacetate.|journal=Nature|volume=209 |issue=5021 |pages=694–696 |year=1966 |pmid=5922128 |doi=10.1038/209694a0}}</ref> Several studies have shown iodoacetate has anti-tumor effects. In 2002 ] showed that "a single IAA treatment of tumor-bearing mice significantly increased the levels of plasma lactate dehydrogenase (LDH) activity, while it also significantly decreased the levels of plasma glucose and liver total protein, RNA and DNA, compared to normal controls."<ref>{{cite journal |author1=Fahim, F. A. |author2=Esmat, A. Y. |author3=Mady, E. A. |author4=Ibrahim, E. K. | title = Antitumor Activities of Iodoacetate and Dimethylsulphoxide Against Solid Ehrlich Carcinoma Growth in Mice | journal = Biological Research | year = 2003 | volume = 36 | issue = 2 | pages = 253–262 | pmid = 14513720 | doi = 10.4067/S0716-97602003000200015 | doi-access = free}}</ref> In 1975 Melvin S. Rhein, Joyce A. Filppi and Victor S. Moore showed that iodoacetate improved the immune response of bone marrow.<ref>{{cite journal |author1=Rhein, M. S. |author2=Filppi, J. A. |author3=Moore, V. S. | title = Effect of Iodoacetate on the Bone Marrow Immunocompetence of AKR Mice | journal = Cancer Research | year = 1975 | volume = 35 | issue = 6 | pages = 1514–1519 | pmid = 1093673 | url = http://cancerres.aacrjournals.org/content/35/6/1514.full.pdf}}</ref> In 1966 Charles A. Apffel, Barry G. Arnason & John H. Peters showed anti-tumor activity for iodoacetate.<ref>{{cite journal |author1=Apffel, C. A. |author2=Arnason, B. G. |author3=Peters, J. H. | title = Induction of tumour immunity with tumour cells treated with iodoacetate | journal = Nature | year = 1966 | volume = 209 | issue = 5021 | pages = 694–696 | pmid = 5922128 | doi = 10.1038/209694a0 | bibcode = 1966Natur.209..694A |s2cid=4296138}}</ref>


==As a disinfection by-product==
==See also==

* ]
] is a naturally occurring ion that can be found in many source waters and it is easily ] by wastewater disinfectants. One of the products of iodide oxidation is ] or ] (HOI and {{chem2|OI−}} respectively) which are capable of reacting with background organic materials to generate iodinated ]s (DBPs) including iodoacetic acid. In a study performed by Plewa, et al., IAA was determined to be one of the most cytotoxic of those studied, with a ] on the order of magnitude of 10<sup>−5</sup> M. It was the most genotoxic of more than 60 DBPs studied and is the most genotoxic DBP identified thus far.<ref name=>{{cite journal|last1=Plewa|first1=Michael J.|last2=Wagner|first2=Elizabeth D.|last3=Richardson|first3=Susan D.|last4=Thruston|first4=Alfred D. Jr.|last5=Woo|first5=Yin-Tak|last6=McKague|first6=A. Bruce|title=Chemical and Biological Characterization of Newly Discovered Iodoacid Drinking Water Disinfection Byproducts|journal=Environmental Science & Technology|date=2004|volume=38|issue=18|pages=4713–4722|bibcode=2004EnST...38.4713P|doi=10.1021/es049971v|pmid=15487777}}</ref> Iodoacetic acid has exhibited traits indicating it as a potential ], however, it has not been proven to be carcinogenic.<ref name=>{{cite journal |last1=Wei |first1=Xiao |last2=Wang |first2=Shu |last3=Zheng |first3=Weiwei |last4=Wang |first4=Xia |last5=Liu |first5=Xiaolin |last6=Jiang |first6=Songhui |last7=Pi |first7=Jingbo |last8=Zheng |first8=Yuxin |last9=He|first9=Gengsheng|last10=Qu|first10=Weidong|title=Drinking Water Disinfection Byproduct Iodoacetic Acid Induces Tumorigenic Transformation of NIH3T3 Cells|journal=Environmental Science & Technology|date=2013|volume=47|issue=11 |pages=5913–5920 |doi=10.1021/es304786b|pmid=23641915 |bibcode=2013EnST...47.5913W}}</ref> The trend continues in ], with iodoacetic acid's potency surpassing that of its brominated and chlorinated analogs.<ref name=>{{cite journal|last1=Richard|first1=Ann M.|last2=Hunter|first2=E. Sidney III|title=Quantitative Structure-Activity Relationships for the Developmental Toxicity of Haloacetic Acids in Mammalian Whole Embryo Culture|journal=Teratology|date=1996|volume=53|issue=6|pages=352–360|pmid=8910981|doi=10.1002/(SICI)1096-9926(199606)53:6<352::AID-TERA6>3.0.CO;2-1}}</ref> Its toxicity correlates to its ability as an ], which will modify ] residues in proteins.<ref name=>{{cite web|title=Product #35603|url=http://www.piercenet.com/product/iodoacetic-acid|website=Thermo Scientific. Pierce Protein Biology Products.}}</ref> ] are the most toxic, with toxicity increasing with halogen size. Iodoacetic acid is more toxic than ] and much more toxic than ].<ref>{{cite journal|last1=Richardson|first1=Susan D.|last2=Plewa|first2=Michael J.|last3=Wagner|first3=Elizabeth D.|last4=Shoeny|first4=Rita|last5=DeMarini|first5=David M|title=Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research|journal=Mutation Research|date=2007|volume=636|issue=1–3|pages=178–242|pmid=17980649|doi=10.1016/j.mrrev.2007.09.001}}</ref>


==References== ==References==
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==Further reading== ==Further reading==
⚫ * {{cite journal |author1=Knap, A. K. |author2=Pratt, R. F. | title = Inactivation of the RTEM-1 cysteine beta-lactamase by iodoacetate. The nature of active-site functional groups and comparisons with the native enzyme | journal = ] | year = 1991 | volume = 273 | issue = 1 | pages = 85–91 |doi=10.1042/bj2730085 | pmid = 1989590 | pmc = 1149883}}
* {{cite journal
⚫ * {{cite journal | author = Dickens, F. | title = Interaction of halogenacetates and SH compounds. The reaction of halogenacetic acids with glutathione and cysteine. The mechanism of iodoacetate poisoning of glyoxalase | journal = ] | year = 1933 | volume = 27 | issue = 4 | pages = 1141–1151 | doi = 10.1042/bj0271141 | pmid = 16745202 | pmc = 1253000}}
| journal = ]
| year = 1991
| volume = 273
| pages = 85–91
⚫ | title = Inactivation of the RTEM-1 cysteine beta-lactamase by iodoacetate. The nature of active-site functional groups and comparisons with the native enzyme
| author = A. K. Knap and R. F. Pratt | url = http://www.biochemj.org/bj/273/bj2730085.htm
| pmid=1989590}}
* {{cite journal
| journal = ]
| year = 1933
| volume = 27
| pages = 1141–1151
⚫ | title = Interaction of halogenacetates and SH compounds. The reaction of halogenacetic acids with glutathione and cysteine. The mechanism of iodoacetate poisoning of glyoxalase.
| author = Dickens F
| pmid = 16745202
| url = http://www.biochemj.org/bj/027/bj0271141.htm
| issue = 4
| pmc = 1253000}}


==External links== ==External links==
* The ] online database for peptidases and their inhibitors: * The ] online database for peptidases and their inhibitors: {{dead link|date=April 2017 |bot=InternetArchiveBot |fix-attempted=yes}}


{{DEFAULTSORT:Iodoacetic Acid}}
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