Iodoacetic acid: Difference between revisions

{{jargon|date=April 2024}}

| Verifiedfields = changed

|

ImageFile = Iodoacetic-acid-2D-skeletal.png

| ImageSize = 150px

| ImageName = Skeletal formula

| ImageFile1 = Iodoacetic-acid-3D-vdW.png

| ImageSize1 = 160px

| ImageName1 = Space-filling model

| ImageCaption1 = {{legend|rgb(64, 64, 64)|[[Carbon]], C}}{{legend|white|[[Hydrogen]]}}{{legend|red|[[Oxygen]], O}}{{legend|rgb(128, 0, 128)|[[Iodine]], I}}

| PIN = Iodoacetic acid

| OtherNames =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| CASNo_Ref = {{cascite|correct|CAS}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = WF5188V710

| PubChem= 5240

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 74571

| SMILES=C(C(=O)O)I

}}

| Formula = {{chem2|ICH2CO2H}}

| C=2|H=3|I=1|O=2

| =

|

MeltingPtC=81

| 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=

}}

|={{Chembox Hazards

| = [http://msds.chem.ox.ac.uk/IO/iodoacetic_acid.html Oxford MSDS]

| GHSPictograms = {{GHS06}}{{GHS05}}

| GHSSignalWord = danger

| HPhrases = {{HPhrases|H301|H314}}

| PPhrases = {{PPhrases|P280|P260|P301+P310+P330|P331|P303+P361+P353|P305+P351+P338|P310}}

| GHS_ref = <ref>GHS: [https://gestis.dguv.de/data?name=510268 GESTIS 510268]</ref>

| FlashPt=

| AutoignitionPt =

}}

| Section8 = {{Chembox Related

| OtherCompounds = {{ubl|[[Acetic acid]]|[[Fluoroacetic acid]]|[[Chloroacetic acid]]|[[Bromoacetic acid]]|[[Tribromoacetic acid]][[Iodoacetamide]]|[[Ethyl bromoacetate]]}}

}}

'''Iodoacetic acid''' is a derivative of [[acetic acid]]. It is a toxic compound, because, like many alkyl , it is an [[alkylating agent]].

It reacts with [[cysteine]] residues in [[proteins]]. It is often used to modify [[thiol|{{chem2|\sSH}} groups]] to prevent the re-formation of [[disulfide bond]]s after the reduction of [[cystine]] residues to cysteine during [[protein sequencing]].

In 1929, Dr. [[Einar Lundsgaard]] (1899-1968) discovered that [[muscle]] [[poisoned]] [[in vitro]] with iodoacetic acid is unable to produce [[Lactic acid|lactate]] as [[glycolysis]] from muscle [[glycogen]] 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 [[Brian McArdle|Dr. Brian McArdle]] 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>

==Peptidase inhibitor==

Iodoacetate is an irreversible inhibitor of all [[cysteine protease|cysteine peptidases]], with the mechanism of inhibition occurring from alkylation of the catalytic cysteine residue (see schematic). In comparison with its amide derivative, [[iodoacetamide]], iodoacetate reacts substantially . 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 is the reason for the increased activity of <ref>{{cite journal|author=, L|title=Deuterium isotope effects on papain acylation. Evidence for lack of general base catalysis and for enzyme-leaving group interaction|journal= |volume=98|issue=2 |pages=369–374 |=1979|pmid=488108}}</ref>[[Image:Iodoacetic acid mechanism.svg|thumb|left||Mechanism of irreversible inhibition of cysteine with iodoacetate.]]{{clearleft}}

Several studies have shown iodoacetate has anti-tumor effects. In 2002 [[Fawzia Fahim]] 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 |=Fahim, Esmat, A Mady Ibrahim |title=Antitumor Activities of Iodoacetate and Dimethylsulphoxide Against Solid Ehrlich Carcinoma Growth in Mice |journal= |volume=36 |issue=2 |pages=253–262 | 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 |= S. , A. S. |title=Effect of Iodoacetate on the Bone Marrow Immunocompetence of AKR Mice|journal=Cancer Research|volume=35 |= |= |pmid=1093673 |= }}</ref> In 1966 Charles A. Apffel, Barry G. Arnason & John H. Peters showed anti-tumor activity for iodoacetate.<ref>{{cite journal |= A. , G. H. |title=Induction of tumour immunity with tumour cells treated with iodoacetate|journal=Nature|volume=209 |issue=5021 |pages=694–696 | pmid=5922128 |doi=10.1038/209694a0}}</ref>

==As a disinfection by-product==

[[Iodide]] is a naturally occurring ion that can be found in many source waters and it is easily [[oxidized]] by wastewater disinfectants. One of the products of iodide oxidation is [[hypoiodous acid]] or [[hypoiodite]] (HOI and {{chem2|OI−}} respectively) which are capable of reacting with background organic materials to generate iodinated [[disinfection by-product]]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 [[median lethal dose]] on the order of magnitude of 10⁻⁵ M. It was the most genotoxic of more than 60 DBPs studied and is the most genotoxic DBP identified thus far.<ref name=[4]>{{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 [[carcinogen]], however, it has not been proven to be carcinogenic.<ref name=[7]>{{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 [[teratogenicity]], with iodoacetic acid's potency surpassing that of its brominated and chlorinated analogs.<ref name=[5]>{{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 [[alkylating agent]], which will modify [[cysteine]] residues in proteins.<ref name=[9]>{{cite web|title=Product #35603|url=http://www.piercenet.com/product/iodoacetic-acid|website=Thermo Scientific. Pierce Protein Biology Products.}}</ref> [[Haloacetic acids|Monohaloacetic acids]] are the most toxic, with toxicity increasing with halogen size. Iodoacetic acid is more toxic than [[bromoacetic acid]] and much more toxic than [[chloroacetic acid]].<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>

| title = Inactivation of the RTEM-1 cysteine beta-lactamase by iodoacetate. The nature of active-site functional groups and comparisons with the native enzyme

| title = Interaction of halogenacetates and SH compounds. The reaction of halogenacetic acids with glutathione and cysteine. The mechanism of iodoacetate poisoning of glyoxalase.

* The [[MEROPS]] online database for peptidases and their inhibitors: [http://meropstest.sanger.ac.uk/cgi-bin/smi_summary?mid=J00006 Iodoacetate]

{{DEFAULTSORT:Iodoacetic Acid}}

[[Category: acids]]

[[Category:Organoiodides]]

[[Category:Iodoacetates| ]]