甲基胂酸 | 124-58-3

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 中文名称: 甲基胂酸
• 中文别名: 甲基砷酸
• 英文名称: methylarsonic Acid
• 英文别名: monomethylarsonic acid；MMA^V；MMA
• CAS: 124-58-3
• 化学式: CH₅AsO₃
• 分子量: 139.97
• InChiKey: QYPPRTNMGCREIM-UHFFFAOYSA-N

物化性质

• 熔点：
  161°
• 沸点：
  393.3±25.0 °C(Predicted)
• 物理描述：
  Solid
• 颜色/状态：
  Monoclinic, spear-shaped plates from absolute alcohol
• 味道：
  Pleasant acid taste
• 溶解度：
  In water, 2.56X10+5 mg/l @ 20 °C.
• 蒸汽压力：
  <7.5X10-8 mm Hg @ 25 °C
• 稳定性/保质期：

  STABLE

• 分解：
  WHEN HEATED TO DECOMPOSITION IT EMITS TOXIC FUMES OF /ARSENIC/.
• 腐蚀性：
  Mildly corrosive
• 解离常数：
  pKa1= 4.1; pKa2= 9.02

计算性质

• 辛醇/水分配系数(LogP)：
  -1.03
• 重原子数：
  5
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

摄入富含砒霜的葡萄酒后，大约10%的砒霜以亚砷酸盐的形式排出，但大部分砒霜被甲基化成甲基亚砷酸和二甲基砷酸并排出体外。

AFTER INGESTION /SRP: BY HUMANS/ OF ARSENIC-RICH WINE, APPROX 10% OF THE ARSENIC WAS EXCRETED AS ARSENITE, BUT THE MAJORITY OF ARSENIC WAS METHYLATED TO METHYLARSONIC ACID & DIMETHYLARSINIC ACID & EXCRETED.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大肠内容物存在的情况下，但不包括小肠，大鼠在体外形成了少量甲基硒酸和二甲基硒酸。

IN THE PRESENCE OF CECAL CONTENT, BUT NOT SMALL INTESTINE, SMALL AMOUNTS OF METHYLARSONIC ACID & DIMETHYLARSINIC ACID WERE FORMED BY THE RAT IN VITRO.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在铜冶炼工人首次空腹尿样中，接触无机砷的工人和未接触的对照组中，有20%的总砷以甲基胂酸的形式排出。

IN FIRST VOID URINE SAMPLES FROM COPPER SMELTER WORKERS EXPOSED TO INORG ARSENIC & FROM NONEXPOSED CONTROLS 20% OF TOTAL ARSENIC WAS EXCRETED AS METHYLARSONIC ACID.

来源:Hazardous Substances Data Bank (HSDB)

代谢

人体可以通过迅速且高效的处理过程，将中剂量的砒霜甲基化，转化为单甲基砒酸和二甲基砒酸，这些物质可以迅速通过尿液排出体外。

THE HUMAN ORGANISM CAN COPE WITH MODERATE DOSES OF ARSENIC BY A RAPID & EFFICIENT METHYLATION PROCESS GIVING MONOMETHYLARSONIC ACID & DIMETHYLARSINIC ACID WHICH ARE RAPIDLY ELIMINATED IN THE URINE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

砷主要通过吸入或摄入进入人体，其次是皮肤接触。进入人体后，砷会在全身分布，根据需要被还原成亚砷酸盐，然后通过亚砷酸盐甲基转移酶被甲基化成单甲基砷（MMA）和二甲基硅酸（DMA）。砷及其代谢物主要通过尿液排出体外。已知砷能诱导金属结合蛋白金属硫蛋白，金属硫蛋白通过结合砷和其他金属，使它们生物学上失活，并作为抗氧化剂，从而减少砷和其他金属的有毒效果。

Arsenic is absorbed mainly by inhalation or ingestion, as to a lesser extent, dermal exposure. It is then distributed throughout the body, where it is reduced into arsenite if necessary, then methylated into monomethylarsenic (MMA) and dimethylarsenic acid (DMA) by arsenite methyltransferase. Arsenic and its metabolites are primarily excreted in the urine. Arsenic is known to induce the metal-binding protein metallothionein, which decreases the toxic effects of arsenic and other metals by binding them and making them biologically inactive, as well as acting as an antioxidant. (L20)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

砷及其代谢物通过多种机制干扰ATP的产生。在柠檬酸循环层面，砷抑制了丙酮酸脱氢酶，并通过与磷酸竞争，解偶联氧化磷酸化，从而抑制了与能量相关的NAD+的还原、线粒体呼吸和ATP的合成。过氧化氢的产生也增加了，这可能会形成活性氧物种和氧化应激。砷的致癌性受到砷与微管蛋白结合的影响，这会导致非整倍体、多倍体和有丝分裂的停滞。其他砷蛋白靶点的结合也可能导致DNA修复酶活性的改变、DNA甲基化模式的改变和细胞增殖的增加。(T1, A17)

Arsenic and its metabolites disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. Arsenic's carginogenicity is influenced by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. The binding of other arsenic protein targets may also cause altered DNA repair enzyme activity, altered DNA methylation patterns and cell proliferation. (T1, A17)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：甲基胂酸

IARC Carcinogenic Agent:Methylarsonic acid

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第100C卷：(2012) 砷、金属、纤维和尘埃

IARC Monographs:Volume 100C: (2012) Arsenic, Metals, Fibres, and Dusts

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

3, 其对人类致癌性无法分类。

3, not classifiable as to its carcinogenicity to humans. (L135)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

奶牛被喂食含有MAA的棉籽饲料。MAA对奶牛没有影响，在组织或牛奶中几乎没有残留物积累。MAA似乎很难从肠道吸收，并且会迅速通过尿液排出体外。

...DAIRY COWS /WERE FED/ COTTONSEED RATION CONTAINING MAA. THE MAA HAD NO EFFECT ON COWS, WITH VERY LITTLE RESIDUE ACCUMULATING IN TISSUES OR MILK. THE MAA APPEARED TO BE POORLY ABSORBED FROM INTESTINAL TRACT & WAS RAPIDLY EXCRETED IN URINE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

牛奶或食用组织中的砷含量，以及食用含有30 PPM酸性物质的5磅棉籽粉9周的奶牛，并没有显著增加；同样，接受含有高达3 PPM甲基砷酸的饮食的母鸡所产蛋和肉中的砷含量也没有显著增加。

ARSENIC CONTENT OF MILK OR EDIBLE TISSUES OF COWS FED FOR 9 WK WITH 5 LB COTTONSEED MEAL CONTAINING 30 PPM OF ACID WAS NOT SIGNIFICANTLY INCREASED; NOR WAS ARSENIC CONTENT OF EGGS AND MEAT OF HENS RECEIVING DIETS CONTAINING UP TO 3 PPM OF METHANEARSONIC ACID.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

棉花/棉籽吸收MAA /甲基砷酸/和MSMA /单钠甲基砷酸/比DSMA /二钠甲基砷酸/更容易。随着温度的升高，(14)C DSMA的吸收倾向增加。/甲基砷酸，二钠盐/

/COTTON/ COTYLEDONS ABSORBED MAA /METHANEARSONIC ACID/ & MSMA /MONOSODIUM METHANEARSONIC ACID/ MORE READILY THAN DSMA. ... ABSORPTION OF (14)C DSMA TENDED TO INCREASE WITH TEMPERATURE. /METHANEARSONIC ACID, DISODIUM SALT/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 海关编码：
  2931900036
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 2759
• 储存条件：
  库房应保持通风、低温和干燥，并与其他食品原料分开储存和运输。

SDS

第一部分：化学品名称

制备方法与用途

用途：用于制药工业。

类别：有毒物品

毒性分级：中毒

急性毒性：

• 口服 - 大鼠 LD50: 961 毫克/公斤
• 口服 - 小鼠 LD50：1800 毫克/公斤

可燃性危险特性：

• 可燃，火场排出砷氧化物、辛辣刺激烟雾。

储运特性：

• 库房通风低温干燥；
• 与食品原料分开储运。

灭火剂：

• 二氧化碳
• 砂土
• 水

职业标准：

• 时间加权平均容许浓度 (TWA)：0.2 毫克/立方米（砷）
• 短时间暴露极限值 (STEL)：0.6 毫克/立方米（砷）

反应信息

• 作为反应物：
  描述：

  甲基胂酸 在 盐酸 、 二氧化硫 、 potassium iodide 作用下， 以 水 为溶剂， 反应 4.0h， 以56%的产率得到甲基-亚胂二碘化物
  参考文献：
  名称：

  Comparative Inhibition of Yeast Glutathione Reductase by Arsenicals and Arsenothiols

  摘要：

  Tri(gamma-glutamylcysteinylglycinyl)trithioarsenite (As-III(GS)(3)) is formed in cells and is a more potent mixed-type inhibitor of the reduction of glutathione disulfide (GSSG) by yeast glutathione (GSH) reductase than either arsenite (As-III) or GSH. The present work examines the effects of valence and complexation of arsenicals with GSH or L-cysteine (Cys) upon potency as competitive inhibitors of the reduction of GSH disulfide (GSSG) by yeast GSH reductase. Trivalent arsenicals were more potent inhibitors than their pentavalent analogs, and methylated trivalent arsenicals were more potent inhibitors than was inorganic trivalent As. Complexation of either inorganic trivalent As or methylarsonous diiodide ((CH3AsI2)-I-III) with Cys or GSH produced inhibitors of GSH reductase that were severalfold more potent than the parent arsenicals. In contrast, dimethylarsinous iodide ((CH3)(2)(AsI)-I-III) was a more potent inhibitor than its complexes with either GSH or Cys. Complexes of CH3AsIII with GSH (CH3AsIII(GS)(2)) or with Cys (CH3AsIII(Cys)(2)) were the most potent inhibitors, with K-i's of 0.009 and 0.018 mM, respectively. Inhibition of GSH reductase by arsenicals or arsenothiols was prevented by addition of meso-2,3-dimercaptosuccinic acid (DMSA) to a mixture of enzyme, GSSG, and inhibitor before addition of NADPH. DMSA added to the reaction mixture after NADPH reversed inhibition by (CH3)(2)(AsI)-I-III but had little effect on inhibition by (CH3AsI2)-I-III, CH3AsIII(GS)(2), CH3AsIII(Cys)(2), Or AS(III)(GS)(3). Partial redox inactivation of the enzyme with NADPH increased the inhibitory potency of (CH3AsI2)-I-III and (CH3)(2)(AsI)-I-III and changed the mode of inhibition for (CH3AsI2)-I-III from competitive to noncompetitive. The greater potency of methylated trivalent arsenicals and arsenothiols than of inorganic trivalent As suggests that biomethylation of As could yield species that inhibit reduction of GSSG and alter the redox status of cells.

  DOI：

  10.1021/tx960139g
• 作为产物：
  描述：

  氯甲烷 在 trisodium arsenite 、 水 作用下， 60.0 ℃ 、392.24 kPa 条件下， 生成 甲基胂酸
  参考文献：
  名称：

  Process of methylating sodium ortho arsenite

  摘要：

  公开号：

  US02695306A1
• 作为试剂：
  描述：

  丁酮 在 卡可基氧 、 甲基胂酸 、 氨 、 双氧水 、 溶剂黄146 作用下， 以 水 、 乙二醇 为溶剂， 以95%的产率得到butan-2-one azine
  参考文献：
  名称：

  METHOD FOR PRODUCING KETAZINE COMPOUND

  摘要：

  公开号：

  EP2123632B1

文献信息

• PYRIDO-/AZEPINO-BENZOFURAN AND PYRIDO-/AZEPINO-BENZOTHIOPHENE MCH-1 ANTAGONISTS, METHODS OF MAKING, AND USE THEREOF
  申请人：Albany Molecular Research, Inc.

  公开号：US20140163012A1

  公开（公告）日：2014-06-12

  Novel MCH-1 receptor antagonists are disclosed. These compounds are used in the treatment of various disorders, including obesity, anxiety, depression, non-alcoholic fatty liver disease, and psychiatric disorders. Methods of making these compounds are also described.

  新型MCH-1受体拮抗剂被披露。这些化合物用于治疗包括肥胖、焦虑、抑郁、非酒精性脂肪肝病和精神障碍在内的各种疾病。制造这些化合物的方法也进行了描述。
• Demethylation of Methylated Arsenic Species during Generation of Arsanes with Tetrahydridoborate(1−) in Acidic Media
  作者：Karel Marschner、Stanislav Musil、Jiří Dědina

  DOI：10.1021/acs.analchem.6b00735

  日期：2016.6.21

  reaction of THB with HCl, H2SO4, and HClO4, while HG from CH3COOH or TRIS buffer after prereduction with l-cysteine resulted in the formation of only the corresponding hydrides. In the case of HNO3 formation of corresponding hydrides was preserved for MAsV and DMAsV but not for TMAsVO. The extent of demethylation strongly depends on concentration of the acid and THB. It can be strongly suppressed in

  挥发性氢化物（HG）生成过程中的脱甲基化，即通过四氢硼酸钠（1-）（THB）的反应，由单甲基砷酸（MAs V），二甲基砷酸（DMAs V）和三甲基ar氧化物（TMAs V O）形成非对应的a烷）在分析条件下用不同的酸进行了研究和表征。在THB与HCl，H 2 SO 4和HClO 4反应过程中发现MAs V，DMAs V和TMAs V O明显脱甲基，而CH 3 COOH或TRIS缓冲液中的HG预先还原为1则产生HG。-半胱氨酸导致仅形成相应的氢化物。在HNO 3的情况下，对于MAs V和DMAs V保留了相应的氢化物形成，对于TMA V O则没有保留。脱甲基化程度强烈取决于酸和THB的浓度。在HCl介质中，可以通过在THB与MAs V，DMAs V或TMAs V O反应之前用最佳浓度的酸部分水解THB来强力抑制它。看来脱甲基是由于THB特定水解产物的作用（最有可能是第一个和第二个）。
• Methylated Phenylarsenical Metabolites Discovered in Chicken Liver
  作者：Hanyong Peng、Bin Hu、Qingqing Liu、Jinhua Li、Xing-Fang Li、Hongquan Zhang、X. Chris Le

  DOI：10.1002/anie.201700736

  日期：2017.6.6

  the liver of chickens fed 3-nitro-4-hydroxyphenylarsonic acid (ROX), a feed additive in poultry production that is still in use in several countries. Methyl-3-nitro-4-hydroxyphenylarsonic acid (methyl-ROX), methyl-3-amino-4-hydroxyphenylarsonic acid (methyl-3-AHPAA), and methyl-3-acetamido-4-hydroxyphenylarsonic acid (or methyl-N-acetyl-ROX, methyl-N-AHPAA) were identified in such chicken livers, and

  我们报告了在饲喂3-硝基-4-羟基苯ar酸（ROX）的鸡的肝脏中发现了三种与毒理学相关的甲基化苯基砷代谢产物，ROX是家禽生产中的饲料添加剂，目前仍在一些国家使用。甲基-3-硝基-4-羟基苯基ar酸（methyl-ROX），甲基-3-氨基-4-羟基苯基ar酸（methyl-3-AHPAA）和甲基-3-乙酰氨基-4-羟基苯基ar酸（或甲基-N在此类鸡肝中鉴定出了（-乙酰-ROX，甲基-N-AHPAA），即使经过五天的清除期，甲基-ROX的浓度也高达90μgkg-1。这些新发现的甲基化代谢物是由涉及三价苯基砷酸底物S-腺苷甲硫氨酸的反应形成的，砷（+3氧化态）甲基转移酶As3MT表明这些化合物是通过在酶促过程中向三价苯基砷底物上加成甲基而形成的。三价苯基砷化合物的IC50值比五价苯基砷化合物的IC50值低300-30 000倍。
• IMMUNE RESPONSE MODIFIER COMPOSITIONS AND METHODS
  申请人：Stoermer Doris

  公开号：US20100158928A1

  公开（公告）日：2010-06-24

  The present invention provides an immune response modifier (IRM) composition that includes an IRM moiety and a second active moiety covalently linked to the IRM moiety, wherein the covalent link comprises a labile bond directly attached to the IRM moiety.

  本发明提供了一种免疫应答调节剂（IRM）组合物，包括一个与IRM基团共价连接的第二活性基团，其中共价连接包括直接连接到IRM基团的不稳定键。
• IMMUNE RESPONSE MODIFIER CONJUGATES
  申请人：Stoermer Doris

  公开号：US20090035323A1

  公开（公告）日：2009-02-05

  The present invention provides IRM conjugates that includes an IRM moiety and a second active moiety covalently linked to the IRM moiety in which the covalent link does not depend on UV irradiation.

  本发明提供了IRM共轭物，其中包括一个IRM基团和一个第二活性基团，该第二活性基团与IRM基团以共价键连接，且该共价键不依赖于紫外辐射。

表征谱图