碘乙酸

碘乙酸
	IUPAC名; Iodoacetic acid
别名	2-碘乙酸
识别
CAS号	64-69-7
PubChem	5240
ChemSpider	5050
SMILES	C(C(=O)O)I;
InChI	1/C2H3IO2/c3-1-2(4)5/h1H2,(H,4,5);
InChIKey	JDNTWHVOXJZDSN-UHFFFAOYAA
ChEBI	74571
性质
化学式	C2H3IO2
摩尔质量	185.95 g·mol−1
熔点	81 °C（354 K）
沸点	208 °C（481 K）
pKa	3.12
危险性
	GHS危险性符号;
GHS提示词	danger
H-术语	H301, H314
P-术语	P280, P260, P301+310+330, P331, P303+361+353, P305+351+338, P310
	若非注明，所有数据均出自标准状态（25 ℃，100 kPa）下。

碘乙酸是乙酸的一种衍生物，分子式为C
2H
3IO
2，碘乙酸有毒性和腐蚀性。与许多卤代烃一样，碘乙酸是一种烷基化试剂。碘乙酸能与蛋白质中的半胱氨酸残基反应，常被用于修饰巯基，以防止在蛋白质胱氨酸残基被还原为半胱氨酸后又重新形成二硫键^[2]^[3]。

Quick Facts 碘乙酸, 识别 ...

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碘乙酸是所有半胱氨酸蛋白酶的不可逆抑制剂，其反应机理如下图所示：

碘乙酸对半胱氨酸肽酶的不可逆抑制机理

与其酰胺衍生物碘乙酰胺相比，碘乙酸盐的烷基化反应速率更慢。这一现象似乎与常规的化学反应性相悖，有报道称，起催化作用的组氨酸中的咪唑𬭩离子和碘乙酸中的羧基负离子间存在有利的相互作用，借此解释碘乙酰胺反应性更强的原因^[2]^[4]。

有研究表明，碘乙酸具有抗肿瘤效果。2002年，生物化学家F. A. Fahim报告称，“与正常对照组相比，对肿瘤小鼠的单次碘乙酸治疗，能明显提高血清乳酸脱氢酶（LDH）的活性水平，同时可显著降低血糖和肝脏总蛋白、RNA和DNA的浓度”^[5]。1975年，有报道称，碘乙酸可能改善骨髓的免疫应答 ^[6]。1966年，有研究指出，碘乙酸盐能用于诱导肿瘤细胞的肿瘤免疫^{[注 1]}治疗^[7]。

碘离子是一种天然存在的离子，可以在许多原水中找到，并且极易被污水消毒液所氧化。其中一种氧化产物是次碘酸（HOI或OI⁻），它拥有与环境有机物反应的强反应性，产生碘化消毒副产物（I-DBPs），如碘乙酸。Plewa等人报道的研究表明，碘乙酸被认为是“饮用水内碘（代）酸类消毒副产物中细胞毒性最强的物质之一”，其半数致死量的中位数为10⁻⁵ M。碘乙酸被确认是迄今为止遗传毒性最强的消毒副产物^[8]。

尽管碘乙酸展现出了潜在致癌物的特征，但尚未被证实具有致癌性^[9]。碘乙酸的致畸性远胜其溴、氯化的类似物 ^[10]。其毒性与其作为烷基化剂的特性相关，会轻易地封闭蛋白质中的半胱氨酸残基^[11]。单卤乙酸的毒性最强，其毒性随着卤原子的大小增加而增加，碘乙酸的毒性强于溴乙酸，远强于氯乙酸 ^[12]。

[注 1]
tumour immunity

碘乙酰胺

[1]
Dippy, J. F. J.; Hughes, S. R. C.; Rozanski, A. The dissociation constants of some symmetrically disubstituted succinic acids. Journal of the Chemical Society. 1959: 2492–2498.
[2]
Smythe CV. The reactions of Iodoacetate and of Iodoacetamide with various Sulfhydryl groups, with Urease, and with Yeast preparations (PDF). J. Biol. Chem. 1936, 114 (3): 601–12.
[3]
Anson ML. The reactions of Iodine and Iodoacetamide with native Egg Albumin. J. Gen. Physiol. 1940, 23 (3): 321–31. PMC 2237930 . PMID 19873158. doi:10.1085/jgp.23.3.321.
[4]
Polgár, L. Deuterium isotope effects on papain acylation. Evidence for lack of general base catalysis and for enzyme-leaving group interaction. European Journal of Biochemistry. 1979, 98 (2): 369–374. PMID 488108. doi:10.1111/j.1432-1033.1979.tb13196.x.
[5]
Fahim, F. A.; Esmat, A. Y.; Mady, E. A.; Ibrahim, E. K. Antitumor Activities of Iodoacetate and Dimethylsulphoxide Against Solid Ehrlich Carcinoma Growth in Mice. Biological Research. 2003, 36 (2): 253–262. PMID 14513720. doi:10.4067/S0716-97602003000200015 .
[6]
Rhein, M. S.; Filppi, J. A.; Moore, V. S. Effect of Iodoacetate on the Bone Marrow Immunocompetence of AKR Mice (PDF). Cancer Research. 1975, 35 (6): 1514–1519. PMID 1093673.
[7]
Apffel, C. A.; Arnason, B. G.; Peters, J. H. Induction of tumour immunity with tumour cells treated with iodoacetate. Nature. 1966, 209 (5021): 694–696. Bibcode:1966Natur.209..694A. PMID 5922128. S2CID 4296138. doi:10.1038/209694a0.
[8]
Plewa, Michael J.; Wagner, Elizabeth D.; Richardson, Susan D.; Thruston, Alfred D., Jr.; Woo, Yin-Tak; McKague, A. Bruce. Chemical and Biological Characterization of Newly Discovered Iodoacid Drinking Water Disinfection Byproducts. Environmental Science & Technology. 2004, 38 (18): 4713–4722. Bibcode:2004EnST...38.4713P. PMID 15487777. doi:10.1021/es049971v.
[9]
Wei, Xiao; Wang, Shu; Zheng, Weiwei; Wang, Xia; Liu, Xiaolin; Jiang, Songhui; Pi, Jingbo; Zheng, Yuxin; He, Gengsheng; Qu, Weidong. Drinking Water Disinfection Byproduct Iodoacetic Acid Induces Tumorigenic Transformation of NIH3T3 Cells. Environmental Science & Technology. 2013, 47 (11): 5913–5920. Bibcode:2013EnST...47.5913W. PMID 23641915. doi:10.1021/es304786b.
[10]
Richard, Ann M.; Hunter, E. Sidney, III. Quantitative Structure-Activity Relationships for the Developmental Toxicity of Haloacetic Acids in Mammalian Whole Embryo Culture. Teratology. 1996, 53 (6): 352–360. PMID 8910981. doi:10.1002/(SICI)1096-9926(199606)53:6<352::AID-TERA6>3.0.CO;2-1.
[11]
Product #35603. Thermo Scientific. Pierce Protein Biology Products. [2023-01-03]. （原始内容存档于2014-12-31）.
[12]
Richardson, Susan D.; Plewa, Michael J.; Wagner, Elizabeth D.; Shoeny, Rita; DeMarini, David M. Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research. Mutation Research. 2007, 636 (1–3): 178–242. PMID 17980649. doi:10.1016/j.mrrev.2007.09.001.

Knap, A. K.; Pratt, R. F. Inactivation of the RTEM-1 cysteine beta-lactamase by iodoacetate. The nature of active-site functional groups and comparisons with the native enzyme. Biochemical Journal. 1991, 273 (1): 85–91. PMC 1149883 . PMID 1989590. doi:10.1042/bj2730085.
Dickens, F. Interaction of halogenacetates and SH compounds. The reaction of halogenacetic acids with glutathione and cysteine. The mechanism of iodoacetate poisoning of glyoxalase. Biochemical Journal. 1933, 27 (4): 1141–1151. PMC 1253000 . PMID 16745202. doi:10.1042/bj0271141.

[7] [注 1]
tumour immunity

[1] [1]
Dippy, J. F. J.; Hughes, S. R. C.; Rozanski, A. The dissociation constants of some symmetrically disubstituted succinic acids. Journal of the Chemical Society. 1959: 2492–2498.

[1936JBC-2] [2]
Smythe CV. The reactions of Iodoacetate and of Iodoacetamide with various Sulfhydryl groups, with Urease, and with Yeast preparations (PDF). J. Biol. Chem. 1936, 114 (3): 601–12.

[3] [3]
Anson ML. The reactions of Iodine and Iodoacetamide with native Egg Albumin. J. Gen. Physiol. 1940, 23 (3): 321–31. PMC 2237930 . PMID 19873158. doi:10.1085/jgp.23.3.321.

[4] [4]
Polgár, L. Deuterium isotope effects on papain acylation. Evidence for lack of general base catalysis and for enzyme-leaving group interaction. European Journal of Biochemistry. 1979, 98 (2): 369–374. PMID 488108. doi:10.1111/j.1432-1033.1979.tb13196.x.

[5] [5]
Fahim, F. A.; Esmat, A. Y.; Mady, E. A.; Ibrahim, E. K. Antitumor Activities of Iodoacetate and Dimethylsulphoxide Against Solid Ehrlich Carcinoma Growth in Mice. Biological Research. 2003, 36 (2): 253–262. PMID 14513720. doi:10.4067/S0716-97602003000200015 .

[6] [6]
Rhein, M. S.; Filppi, J. A.; Moore, V. S. Effect of Iodoacetate on the Bone Marrow Immunocompetence of AKR Mice (PDF). Cancer Research. 1975, 35 (6): 1514–1519. PMID 1093673.

[8] [7]
Apffel, C. A.; Arnason, B. G.; Peters, J. H. Induction of tumour immunity with tumour cells treated with iodoacetate. Nature. 1966, 209 (5021): 694–696. Bibcode:1966Natur.209..694A. PMID 5922128. S2CID 4296138. doi:10.1038/209694a0.

[[4]-9] [8]
Plewa, Michael J.; Wagner, Elizabeth D.; Richardson, Susan D.; Thruston, Alfred D., Jr.; Woo, Yin-Tak; McKague, A. Bruce. Chemical and Biological Characterization of Newly Discovered Iodoacid Drinking Water Disinfection Byproducts. Environmental Science & Technology. 2004, 38 (18): 4713–4722. Bibcode:2004EnST...38.4713P. PMID 15487777. doi:10.1021/es049971v.

[[7]-10] [9]
Wei, Xiao; Wang, Shu; Zheng, Weiwei; Wang, Xia; Liu, Xiaolin; Jiang, Songhui; Pi, Jingbo; Zheng, Yuxin; He, Gengsheng; Qu, Weidong. Drinking Water Disinfection Byproduct Iodoacetic Acid Induces Tumorigenic Transformation of NIH3T3 Cells. Environmental Science & Technology. 2013, 47 (11): 5913–5920. Bibcode:2013EnST...47.5913W. PMID 23641915. doi:10.1021/es304786b.

[[5]-11] [10]
Richard, Ann M.; Hunter, E. Sidney, III. Quantitative Structure-Activity Relationships for the Developmental Toxicity of Haloacetic Acids in Mammalian Whole Embryo Culture. Teratology. 1996, 53 (6): 352–360. PMID 8910981. doi:10.1002/(SICI)1096-9926(199606)53:6<352::AID-TERA6>3.0.CO;2-1.

[[9]-12] [11]
Product #35603. Thermo Scientific. Pierce Protein Biology Products. [2023-01-03]. （原始内容存档于2014-12-31）.

[13] [12]
Richardson, Susan D.; Plewa, Michael J.; Wagner, Elizabeth D.; Shoeny, Rita; DeMarini, David M. Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research. Mutation Research. 2007, 636 (1–3): 178–242. PMID 17980649. doi:10.1016/j.mrrev.2007.09.001.

[2]

[3]

[1]

[4]

[5]

[6]

[注 1]

[7]

[8]

[9]

[10]

[11]

[12]

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碘乙酸

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肽酶抑制剂

潜在的癌症疗法

消毒副产物

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碘乙酸


IUPAC名 Iodoacetic acid
别名	2-碘乙酸
识别
CAS号	64-69-7 ^Y
PubChem	5240
ChemSpider	5050
SMILES	C(C(=O)O)I
InChI	1/C2H3IO2/c3-1-2(4)5/h1H2,(H,4,5)
InChIKey	JDNTWHVOXJZDSN-UHFFFAOYAA
ChEBI	74571
性质
化学式	C₂H₃IO₂
摩尔质量	185.95 g·mol⁻¹
熔点	81 °C（354 K）
沸点	208 °C（481 K）
pK_a	3.12^[1]
危险性
GHS危险性符号
GHS提示词	danger
H-术语	H301, H314
P-术语	P280, P260, P301+310+330, P331, P303+361+353, P305+351+338, P310
若非注明，所有数据均出自标准状态（25 ℃，100 kPa）下。