二甲基卑胂酸 | 55094-22-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机胂酸
• 中文名称: 二甲基卑胂酸
• 英文名称: dimethylarsinous acid
• 英文别名: DMA^III
• CAS: 55094-22-9
• 化学式: C₂H₇AsO
• 分子量: 121.999
• InChiKey: VDEGQTCMQUFPFH-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于水
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  0.23
• 重原子数：
  4
• 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：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2931900090

反应信息

• 作为反应物：
  描述：

  二甲基卑胂酸 在 氧气 作用下， 以 重水 为溶剂， 生成 卡可基氧
  参考文献：
  名称：

  A phase II study of combined chemotherapy with methotrexate, 5-fluorouracil, and low-dose cisplatin (MFP) for histologically diffuse-type advanced and recurrent gastric cancer (KDOG9501)

  摘要：

  Background: Histologically diffuse-type gastric cancer is well known to have a poor prognosis and is often complicated with abdominal and pleural effusions. We evaluated the efficacy of a low dose of cisplatin combined with methotrexate and 5-fluorouracil (MFP therapy) in diffuse-type advanced gastric cancer. Methods: The study group comprised 47 patients. Patients with pleural effusion or ascites were actively enrolled. Methotrexate (30 mg/m(2) per day) plus 5-fluorouracil (600 mg/m(2) per day) was administered on days 1 and 8. Cisplatin (6 mg/m(2) per day) was given daily for 14 days after which there was 14 day's rest. Calcium leucovorin (15 mg) was administered after methotrexate. Results: The overall response rate was 38.3%. Ascites disappeared or decreased in 15 of 23 patients (disappeared in 9). Pleural effusion disappeared or decreased in 6 of 8 patients (disappeared in 4). Of the 21 patients with poor oral intake at study entry, 15 (71.4%) were able to orally ingest food. Hematologic toxicity of grade 3 or higher comprised leukopenia in 10 patients (21.3%) and neutropenia in 9 (19.1%). Nonhematologic toxicity included anorexia and nausea/vomiting, in 1 patient each (2.1%). The median survival time was 211 days. Conclusion: MFP therapy is useful for the management of diffuse-type inoperable and recurrent gastric cancer, even in patients with conditions such as pleural effusion, ascites, or lymphangitis carcinomatosa who have a poor prognosis or cannot eat solid food.

  DOI：

  10.1007/s10120-006-0371-x
• 作为产物：
  描述：

  卡可基氧 在 sodium disulfite 、 硫酸 、 sodium thiosulfate 作用下， 反应 1.0h， 生成 二甲基卑胂酸
  参考文献：
  名称：

  谷胱甘肽共轭砷在大鼠潜在的肝肠循环中。

  摘要：

  通过确定砷的代谢平衡和化学物种，精确研究了砷的代谢途径，以洞察动物物种在砷的代谢和砷在红细胞（RBCs）中的优先积累方面的差异机理。给雄性Wistar大鼠静脉注射单剂量砷（iAs（III）），剂量为2.0 mg As / kg体重，然后测定器官和体液中砷浓度随时间的变化。此外，通过高效液相色谱-电感耦合氩等离子体质谱（HPLC-ICP MS）在阴离子和阳离子交换柱上分析胆汁中的砷。代谢平衡和形态研究表明，砷可能通过与谷胱甘肽（GSH）结合的形式从肝脏排泄而转移到肝肠循环中。iAs（III）在肝脏中以共轭形式[iAs（III）（GS）（3）]甲基化成肝脏中的单（MMA）-和二甲基化（DMA）砷，一部分MMA排泄到胆汁中。以MMA（III）和MMA（V）的形式存在，前者大部分为共轭形式[CH（3）As（III）（GS）（2）]，而后者为非共轭游离形式。在胆汁中未检测到DMA（III）和DMA（

  DOI：

  10.1021/tx0155496

文献信息

• Characterization and Mechanistic Study of the Radical SAM Enzyme ArsS Involved in Arsenosugar Biosynthesis
  作者：Jinduo Cheng、Wenjuan Ji、Suze Ma、Xinjian Ji、Zixin Deng、Wei Ding、Qi Zhang

  DOI：10.1002/anie.202015177

  日期：2021.3.29

  been proposed that arsenosugar biosynthesis involves a key intermediate 5′‐deoxy‐5′‐dimethylarsinoyl‐adenosine (DDMAA), but how DDMAA is produced remains elusive. Now, we report characterization of ArsS as a DDMAA synthase, which catalyzes a radical S‐adenosylmethionine (SAM)‐mediated alkylation (adenosylation) of dimethylarsenite (DMAsIII) to produce DDMAA. This radical‐mediated reaction is redox neutral

  砷糖是一组含砷的核糖苷，主要存在于海藻中，也存在于陆地生物中。有人提出砷糖的生物合成涉及一个关键的中间体5'-脱氧-5'-二甲基ar氨酰基-腺苷（DDMAA），但如何产生DDMAA仍然难以捉摸。现在，我们报告ArsS作为DDMAA合酶的特征，它催化二甲基亚砷酸（DMAs III）的自由基S-腺苷甲硫氨酸（SAM）介导的烷基化（腺苷化））以生成DDMAA。这种自由基介导的反应是氧化还原中性的，无需外部还原剂即可实现多次转换。系统生物学和生化分析表明，DDMAA合酶广泛存在于不同的细菌门中，具有相似的催化效率。这些酶很可能起源于蓝细菌。这项研究揭示了砷糖生物合成的关键步骤，也是自由基SAM化学的新范例，突出了这种酶超家族的催化多样性。
• Speciation of Dimethylarsinous Acid and Trimethylarsine Oxide in Urine from Rats Fed with Dimethylarsinic Acid and Dimercaptopropane Sulfonate
  作者：Xiufen Lu、Lora L. Arnold、Samuel M. Cohen、William R. Cullen、X. Chris Le

  DOI：10.1021/ac034868u

  日期：2003.12.1

  Speciation of arsenic in urine from rats treated with dimethylarsinic acid (DMAV) alone or in combination with dimercaptopropane sulfonate (DMPS) were studied. Methods were developed for the determination of the methylarsenic metabolites, especially trace levels of dimethylarsinous acid (DMAIII) and trimethylarsine oxide (TMAO), in the presence of a large excess of DMAV. Success was achieved by using improved ion-exchange chromatographic separation combined with hydride generation atomic fluorescence detection. Micromolar concentrations of DMAIII were detected in urine of rats fed with a diet supplemented with either 100 μg/g of DMAV or a mixture of 100 μg/g of DMAV and 5600 μg/g of DMPS. No significant difference in the DMAIII concentration was observed between the two groups; however, there was a significant difference in TMAO concentrations. Urine from rats fed with the diet supplemented with DMAV alone contained 73 ± 30 μM TMAO, whereas urine from rats fed with the diet supplemented with both DMAV and DMPS contained only 2.8 ± 1.4 μM TMAO. Solutions containing mixtures of 100 μg/L DMAV or TMAO and 5600 μg/L DMPS did not show reduction of DMAV and TMAO. The significant decrease (p < 0.001) of the TMAO concentration in rats administered with both DMAV and DMPS suggests that DMPS inhibits the biomethylation of arsenic.

  研究了单独或与二巯基丙磺酸盐（DMPS）一起使用二甲基砷酸（DMAV）处理的大鼠尿液中砷的种类。在 DMAV 大量过量的情况下，开发了测定甲基砷代谢物，特别是痕量二甲基砷酸 (DMAIII) 和三甲基砷氧化物 (TMAO) 的方法。通过使用改进的离子交换色谱分离技术和氢化物发生原子荧光检测技术取得了成功。在喂食补充了 100 μg/g DMAV 或 100 μg/g DMAV 与 5600 μg/g DMPS 混合物的大鼠尿液中检测到了微摩尔浓度的 DMAIII。两组大鼠的 DMAIII 浓度无明显差异，但 TMAO 浓度有明显差异。仅以补充 DMAV 的食物喂养的大鼠的尿液中含有 73 ± 30 μM TMAO，而同时以补充 DMAV 和 DMPS 的食物喂养的大鼠的尿液中仅含有 2.8 ± 1.4 μM TMAO。含有 100 μg/L DMAV 或 TMAO 和 5600 μg/L DMPS 的混合物溶液并未显示出 DMAV 和 TMAO 的减少。同时使用 DMAV 和 DMPS 的大鼠体内的 TMAO 浓度明显下降（p < 0.001），这表明 DMPS 可抑制砷的生物甲基化。
• Enzymatic Reduction of Arsenic Compounds in Mammalian Systems:  The Rate-Limiting Enzyme of Rabbit Liver Arsenic Biotransformation Is MMA^V Reductase
  作者：Robert A. Zakharyan、H. Vasken Aposhian

  DOI：10.1021/tx9901231

  日期：1999.12.1

  A unique enzyme, MMA(V) reductase, has been partially purified from rabbit liver by using DEAE-cellulose, carboxymethylcellulose, and red dye ligand chromatography. The enzyme is unique since it is the rate-limiting enzyme in the biotransformation of inorganic arsenite in rabbit liver. The K-m and V-max values were 2.16 x 10(-3) M and 10.3 mu mol h(-1) (mg of protein)(-1) When DMA(V) or arsenate was tested as a substrate, the K-m was 20.9 x 10(-9) or 109 x 10(-3) M, respectively. The enzyme has an absolute requirement for GSH. Other thiols such as DTT or L-cysteine were inactive alone. At a pH below the physiological pH, GSH carried out this reduction, but this GSH reduction in the absence of the enzyme had little if any value at pH 7.4. When the K-m values of rabbit liver arsenite methyltransferase (5.5 x 10(-6) M) and MMA(III) methyltransferase (9.2 x 10(-6)) were compared to that of MMA(V) reductase (2.16 x 10(-3) M), it can be concluded that MMAV reductase was the rate-limiting enzyme of inorganic arsenite biotransformation. MMAV reductase was also present in surgically removed human liver.
• Theoretical Calculations and Reaction Analysis on the Interaction of Pentavalent Thioarsenicals with Biorelevant Thiol Compounds
  作者：Noriyuki Suzuki、Hua Naranmandura、Seishiro Hirano、Kazuo T. Suzuki

  DOI：10.1021/tx700346z

  日期：2008.2.1

  To obtain a rational understanding of the extraordinary interaction of pentavalent thioarsenicals with biorelevant thiol compounds, we carried out ab initio calculations on related arsenic compounds and discussed the correlation between the distribution of observed arsenic species in actual reaction systems and the corresponding calculated reaction enthalpies. Previously, it was considered that pentavalent arsenicals do not form thiol conjugates. However, the dimethylmonothioarsinic acid-glutathione conjugate (DMMTA(v)-GSH) was recentry reported as the first stable conjugate of a pentavalent arsenical with a thiol compound. We carried out detailed analysis of the DMMTAv-GSH formation reaction and demonstrated that this conjugate could be formed nonenzymatically under weakly acidic conditions. On the basis of the ab initio calculations, this conjugation was an exothermic reaction (Delta H = -4.85 kcal/ mol) and gave the minimum energy point during the reaction sequence of DMMTA(v) with a thiol compound. However, in the case of dimethylarsinic acid (DMA(v)), a corresponding oxo acid to DMMTAv, conjugation with a thiol compound is an endothermic reaction (Delta H = +0.06 kcal/mol). The minimum energy point of the reaction sequence of DMAv with a thiol compound was the formation of a trivalent dimethylarsinous acid (DMA(III))-GSH conjugate. Because the formation of arsenic-sulfur bonds is one of the major mechanisms for arsenic toxicity, these energetic results could account for the extraordinary behaviors and toxicities of thioarsenicals in vivo and in vitro in comparison with those of the corresponding oxo acids.
• Animal Species Difference in the Uptake of Dimethylarsinous Acid (DMA^III) by Red Blood Cells
  作者：Yamato Shiobara、Yasumitsu Ogra、Kazuo T. Suzuki

  DOI：10.1021/tx015537k

  日期：2001.10.1

  The animal species difference in the metabolism of arsenic was studied from the viewpoint of the mechanism underlying its distribution in the form of dimethylated arsenic in red blood cells (RBCs). Dimethylarsinic (DMA(V)) and dimethylarsinous (DMA(III)) acids were incubated with rat, hamster, mouse, and human RBCs, and the uptake rates and chemical forms of arsenic were determined. Although DMA(V) was practically not or taken up slowly by RBCs of all the present animal species, DMA(III) was taken efficiently in the order of rat > hamster > human, RBCs of mice taking it up less efficiently and with a different pattern from the former three animals. Further, although DMA(III) taken up by rat RBCs was retained, that by hamster ones was effluxed in the form of DMA(V). The uptake of DMA(III) and efflux of DMAV took place much more slowly in human RBCs than rat and hamster ones. The uptake of DMA(III) by RBCs was inhibited on the oxidation of glutathione with diamide. Incubation of DMA(III), but not of DMA(V), with a hemolysate produced a high molecular weight complex, which increases in the presence of glutathione, suggesting that DMA(III) taken up by RBCs is retained through the formation of a complex with protein(s) specific to animal species, and effluxed from RBCs after being oxidized to DMA(V). These results indicate that DMA is taken up by RBCs in the form of DMA(III), and that the uptake and efflux rates are dependent on the animal species, the effluxed arsenic being DMA(V). The present results suggest that the uptake of DMA by RBCs is an additional contributing factor to the animal species difference in the metabolism of arsenic in addition to the reduction and methylation capacity in the liver.