Wikipedia

Iodoacetic acid

Iodoacetic acid is an organic compound with the chemical formula ICH2CO2H. It is a derivative of acetic acid. It is a toxic compound, because, like many alkyl halides, it is an alkylating agent.

Iodoacetic acid
Skeletal formula
Space-filling model
  Carbon, C
  Hydrogen
  Oxygen, O
  Iodine, I
Names
Preferred IUPAC name
Iodoacetic acid
Other names
2-Iodoacetic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.537 Edit this at Wikidata
UNII
  • InChI=1S/C2H3IO2/c3-1-2(4)5/h1H2,(H,4,5) checkY
    Key: JDNTWHVOXJZDSN-UHFFFAOYSA-N checkY
  • InChI=1/C2H3IO2/c3-1-2(4)5/h1H2,(H,4,5)
    Key: JDNTWHVOXJZDSN-UHFFFAOYAA
  • C(C(=O)O)I
Properties
ICH2CO2H
Molar mass 185.948 g·mol−1
Melting point 81 °C (178 °F; 354 K)
Boiling point 208 °C (406 °F; 481 K)
Acidity (pKa) 3.12[1]
Hazards
GHS labelling:[2]
GHS06: ToxicGHS05: Corrosive
Danger
H301, H314
P260, P280, P301+P310+P330, P303+P361+P353, P305+P351+P338, P310, P331
Safety data sheet (SDS) Oxford MSDS
Related compounds
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

It reacts with cysteine residues in proteins. It is often used to modify −SH groups to prevent the re-formation of disulfide bonds 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 lactate as glycolysis from muscle glycogen is blocked, causing the muscle to result in an electrically silent contracture.[3][4][clarification needed] It was remembering this discovery, that lead 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.[5]

Peptidase inhibitor

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Iodoacetate is an irreversible inhibitor of all 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 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.[6]

 
Mechanism of irreversible inhibition of cysteine peptidases with iodoacetate.

Possible cancer therapy

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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."[7] In 1975 Melvin S. Rhein, Joyce A. Filppi and Victor S. Moore showed that iodoacetate improved the immune response of bone marrow.[8] In 1966 Charles A. Apffel, Barry G. Arnason & John H. Peters showed anti-tumor activity for iodoacetate.[9]

As a disinfection by-product

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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 OI− respectively) which are capable of reacting with background organic materials to generate iodinated disinfection by-products (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.[10] Iodoacetic acid has exhibited traits indicating it as a potential carcinogen, however, it has not been proven to be carcinogenic.[11] The trend continues in teratogenicity, with iodoacetic acid's potency surpassing that of its brominated and chlorinated analogs.[12] Its toxicity correlates to its ability as an alkylating agent, which will modify cysteine residues in proteins.[13] 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.[14]

References

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  1. ^ Dippy, J. F. J.; Hughes, S. R. C.; Rozanski, A. (1959). "The dissociation constants of some symmetrically disubstituted succinic acids". Journal of the Chemical Society: 2492–2498. doi:10.1039/jr9590002492.
  2. ^ GHS: GESTIS 510268
  3. ^ Shorr, E.; Barker, S. B.; Malam, M. (1938-02-18). "The Influence of Iodoacetic Acid on the Respiratory Metabolism of Mammalian Tissues". Science. 87 (2251): 168–169. Bibcode:1938Sci....87..168S. doi:10.1126/science.87.2251.168. ISSN 0036-8075. PMID 17740354.
  4. ^ Lundsgaard, E., Biochem. Z., 217,162 (1930).
  5. ^ Layzer, Robert B. (1985-02-07). "McArdle's Disease in the 1980s". New England Journal of Medicine. 312 (6): 370–371. doi:10.1056/NEJM198502073120609. ISSN 0028-4793. PMID 3855500.
  6. ^ Polgár, L. (1979). "Deuterium isotope effects on papain acylation. Evidence for lack of general base catalysis and for enzyme-leaving group interaction". European Journal of Biochemistry. 98 (2): 369–374. doi:10.1111/j.1432-1033.1979.tb13196.x. PMID 488108.
  7. ^ Fahim, F. A.; Esmat, A. Y.; Mady, E. A.; Ibrahim, E. K. (2003). "Antitumor Activities of Iodoacetate and Dimethylsulphoxide Against Solid Ehrlich Carcinoma Growth in Mice". Biological Research. 36 (2): 253–262. doi:10.4067/S0716-97602003000200015. PMID 14513720.
  8. ^ Rhein, M. S.; Filppi, J. A.; Moore, V. S. (1975). "Effect of Iodoacetate on the Bone Marrow Immunocompetence of AKR Mice" (PDF). Cancer Research. 35 (6): 1514–1519. PMID 1093673.
  9. ^ Apffel, C. A.; Arnason, B. G.; Peters, J. H. (1966). "Induction of tumour immunity with tumour cells treated with iodoacetate". Nature. 209 (5021): 694–696. Bibcode:1966Natur.209..694A. doi:10.1038/209694a0. PMID 5922128. S2CID 4296138.
  10. ^ Plewa, Michael J.; Wagner, Elizabeth D.; Richardson, Susan D.; Thruston, Alfred D. Jr.; Woo, Yin-Tak; McKague, A. Bruce (2004). "Chemical and Biological Characterization of Newly Discovered Iodoacid Drinking Water Disinfection Byproducts". Environmental Science & Technology. 38 (18): 4713–4722. Bibcode:2004EnST...38.4713P. doi:10.1021/es049971v. PMID 15487777.
  11. ^ Wei, Xiao; Wang, Shu; Zheng, Weiwei; Wang, Xia; Liu, Xiaolin; Jiang, Songhui; Pi, Jingbo; Zheng, Yuxin; He, Gengsheng; Qu, Weidong (2013). "Drinking Water Disinfection Byproduct Iodoacetic Acid Induces Tumorigenic Transformation of NIH3T3 Cells". Environmental Science & Technology. 47 (11): 5913–5920. Bibcode:2013EnST...47.5913W. doi:10.1021/es304786b. PMID 23641915.
  12. ^ Richard, Ann M.; Hunter, E. Sidney III (1996). "Quantitative Structure-Activity Relationships for the Developmental Toxicity of Haloacetic Acids in Mammalian Whole Embryo Culture". Teratology. 53 (6): 352–360. doi:10.1002/(SICI)1096-9926(199606)53:6<352::AID-TERA6>3.0.CO;2-1. PMID 8910981.
  13. ^ "Product #35603". Thermo Scientific. Pierce Protein Biology Products.
  14. ^ Richardson, Susan D.; Plewa, Michael J.; Wagner, Elizabeth D.; Shoeny, Rita; DeMarini, David M (2007). "Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research". Mutation Research. 636 (1–3): 178–242. doi:10.1016/j.mrrev.2007.09.001. PMID 17980649.

Further reading

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