阿司匹林铜 | 23642-01-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 阿司匹林铜
• 英文名称: Cu2(asp)4
• 英文别名: Copper aspirinate；dicopper;2-acetyloxybenzoate
• CAS: 23642-01-5
• 化学式: C₃₆H₂₈Cu₂O₁₆
• 分子量: 843.701
• InChiKey: BXBJCCCIFADZBU-UHFFFAOYSA-J

物化性质

• 熔点：
  255 °C (decomp)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  54
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  266
• 氢给体数：
  0
• 氢受体数：
  16

ADMET

代谢

铜主要通过胃肠道吸收，但也可以通过吸入和皮肤吸收。它通过基底外侧膜，可能是通过调节铜转运蛋白，并与血清白蛋白结合运输到肝脏和肾脏。肝脏是铜稳态的关键器官。在肝脏和其他组织中，铜以与金属硫蛋白、氨基酸结合，并与依赖铜的酶相关联的形式储存，然后分配通过胆汁排泄或并入细胞内和细胞外蛋白中。铜输送到外周组织是通过与血清白蛋白、铜蓝蛋白或低分子量复合物结合的血浆完成的。铜可能诱导金属硫蛋白和铜蓝蛋白的产生。膜结合的铜转运腺苷三磷酸酶（Cu-ATPase）将铜离子输送到细胞内和细胞外。体内生理正常水平的铜通过改变铜的吸收速率和数量、分布区域以及排泄来保持恒定。(L277, L279)

Copper is mainly absorbed through the gastrointestinal tract, but it can also be inhalated and absorbed dermally. It passes through the basolateral membrane, possibly via regulatory copper transporters, and is transported to the liver and kidney bound to serum albumin. The liver is the critical organ for copper homoeostasis. In the liver and other tissues, copper is stored bound to metallothionein, amino acids, and in association with copper-dependent enzymes, then partitioned for excretion through the bile or incorporation into intra- and extracellular proteins. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular-weight complexes. Copper may induce the production of metallothionein and ceruloplasmin. The membrane-bound copper transporting adenosine triphosphatase (Cu-ATPase) transports copper ions into and out of cells. Physiologically normal levels of copper in the body are held constant by alterations in the rate and amount of copper absorption, compartmental distribution, and excretion. (L277, L279)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

过量的铜被储存在肝细胞溶酶体中，在那里它与金属硫蛋白结合。当溶酶体饱和，铜在细胞核中积累，导致核损伤时，铜的肝脏毒性被认为会发生。这种损伤可能是由于氧化损伤，包括脂质过氧化。铜抑制含有巯基的酶，如葡萄糖-6-磷酸-1-脱氢酶、谷胱甘肽还原酶和对氧磷酶，这些酶保护细胞免受自由氧自由基的损害。它还影响基因表达，并且是氧化酶如细胞色素C氧化酶和赖氨氧化酶的辅因子。此外，由铜引起的氧化应激被认为会激活酸性鞘磷脂酶，导致神经酰胺的产生，这是一种凋亡信号，同时也会引起溶血性贫血。铜诱导的呕吐是由于迷走神经的刺激。

Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. Copper-induced emesis results from stimulation of the vagus nerve. (L277, T49, A174, L280)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

人们每天必须吸收少量铜，因为铜对健康至关重要。然而，高水平的铜可能有害。极高的铜剂量可能对肝脏和肾脏造成损害，甚至可能导致死亡。铜可能在敏感个体中引发过敏反应。

People must absorb small amounts of copper every day because copper is essential for good health, however, high levels of copper can be harmful. Very-high doses of copper can cause damage to your liver and kidneys, and can even cause death. Copper may induce allergic responses in sensitive individuals. (L278, L279)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服 (L277) ; 吸入 (L277) ; 皮肤给药 (L277)

Oral (L277) ; inhalation (L277) ; dermal (L277)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

吸入高浓度的铜可以导致鼻和喉咙的刺激。摄入高浓度的铜可以引起恶心、呕吐、腹泻、头痛、眩晕和呼吸困难。

Breathing high levels of copper can cause irritation of the nose and throat. Ingesting high levels of copper can cause nausea, vomiting, diarrhea, headache, dizziness, and respiratory difficulty. (L278, L279)

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 海关编码：
  2918229000

反应信息

• 作为反应物：
  描述：

  阿司匹林铜 在 吡啶 作用下， 以 氯仿 为溶剂， 生成 (copper(II)(aspirinate)2(pyridine)2)
  参考文献：
  名称：

  Superoxide dismutase activity of Cu(II)2(aspirinate)4 and its adducts with nitrogen and oxygen donors

  摘要：

  DOI：

  10.1016/s0020-1693(00)91063-6
• 作为产物：
  描述：

  copper(II) choride dihydrate 、 阿司匹林 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 阿司匹林铜
  参考文献：
  名称：

  Superoxide dismutase activity of Cu(II)2(aspirinate)4 and its adducts with nitrogen and oxygen donors

  摘要：

  DOI：

  10.1016/s0020-1693(00)91063-6

文献信息

• WO2007/139731
  申请人：——

  公开号：——

  公开（公告）日：——
• Mononuclear copper(ll) aspirinate or salicylate complexes with methylimidazoles as biomimetic catalysts for oxidative dealkylation of a hindered phenol, oxidation of catechol and their superoxide scavenging activities
  作者：A. Latif Abuhijleh

  DOI：10.1016/j.inoche.2011.02.029

  日期：2011.5

  Mononuclear complex bis(aspirinato) bis(2-methylimidazole) copper(II), Cu(asp)(2) (2-Melm)(2) (1), has been synthesized and spectroscopically characterized. The biomimetic catalytic activities of this complex and our previously characterized complexes, Cu(asp)(2) (1,2-Melm)(2) (2), Cu(Hsal)(2) (1,2-Melm)(2) (3), and Cu(sal)(2-Melm)(3), (4) [H(2)sal = salicylic acid and Melm = methylimidazole], for the oxidation of 3,5-di-tert-butylcatechol to the corresponding o-quinone and the oxidative dealkylation of 2,4,6-tri-tert-butylphenol to 2,6-di-tert-butyl-1,4-benzoquinone and 4,6-di-tert-butyl-1,2-benzoquinone as the main products are reported. Complexes 1 and 2 are found to be potent SOD mimics and their SOD activities are compared with those obtained previously for complexes 3 and 4. (C) 2011 Elsevier B.V. All rights reserved.
• ——
  作者：S. H. Tarulli、O. V. Quinzani、J. Dristas、E. J. Baran

  DOI：10.1023/a:1010134702443

  日期：——

  Complexes of Cu(II) with substituted o-acetoxy benzoic acids (5-haloaspirines, X-asp) with and without pyridine (py), of composition [Cu-2(X-asp)(4)] and [Cu(X-asp)(2)(py)(2)] have been synthesized and characterized. Electronic and vibrational spectroscopic data of these complexes are reported. Its thermal behaviour was investigated by thermogravimetry and differential thermal analysis. In all complexes, the haloaspirinate ligands decompose in two or three steps, starting with the break up of the coordinated acetoxy groups. CuO is obtained as the final pyrolysis residue in all cases.