铜-乙二胺络合物 | 13426-91-0

• 分子结构分类: 有机化合物 - 有机盐 - 有机金属盐
• 中文名称: 铜-乙二胺络合物
• 英文名称: [copper(II)(ethylenediamine)2](2+)
• 英文别名: bis(ethylenediamine)copper(II)(2+)；bis-ethylenediaminecopper(II)；[Cu(ethylenediamine)2](2+)；Cu(ethylenediamine)2(2+)；copper;ethane-1,2-diamine
• CAS: 13426-91-0
• 化学式: C₄H₁₆CuN₄
• 分子量: 183.744
• InChiKey: ATSGLBOJGVTHHC-UHFFFAOYSA-N

物化性质

• 颜色/状态：
  Purple liquid
• 气味：
  Ammoniacal

计算性质

• 辛醇/水分配系数(LogP)：
  -2.19
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  104
• 氢给体数：
  4
• 氢受体数：
  4

ADMET

代谢

从Cu(II)配合物与生物还原剂如抗坏血酸、谷胱甘肽、乙酰半胱氨酸和对苯二酚的反应中产生羟基自由基（.OH）已被电子自旋共振（ESR）自旋捕获实验所证实。所使用的Cu(II)配合物包括：Cu(II)-(CyHH)2 (CyHH, 环(L-组氨酸-L-组氨酸))、Cu(II)(OP)2 (OP, 邻菲啰啉)、Cu(II)(HGG) (HGG, L-组氨酸-甘氨酰甘氨酸)和Cu(II)(en)2 (en, 乙二胺)。在自旋捕获剂POBN和二甲亚砜的存在下，抗坏血酸与所有在此使用的Cu(II)配合物反应生成了alpha-(吡啶-4-N-氧化物)-N-叔丁基氮氧化物（POBN-CH3）的甲基自由基加成物，表明产生了.OH。谷胱甘肽、N-乙酰半胱氨酸和对苯二酚与Cu(II)(CyHH)2和Cu(II)(OP)2反应生成了POBN-CH3，而这些还原剂与Cu(II)(HGG)或Cu(II)(en)2没有反应。在相同的条件下，研究了Cu(II)配合物与还原剂反应混合物引起的DNA链断裂。将抗坏血酸添加到这四种Cu(II)配合物和DNA的混合物中，导致了DNA链的断裂。在所使用的浓度范围内，谷胱甘肽、N-乙酰半胱氨酸或对苯二酚与Cu(II)-(HGG)或Cu(II)(en)2的反应混合物没有引起DNA链断裂。这里获得的结果表明POBN-CH3形成与DNA链断裂之间存在良好的相关性。因此，DNA链断裂可能是由一些Cu(II)配合物在氧气的条件下与生物还原剂反应产生的.OH引起的。由于抗坏血酸、谷胱甘肽和N-乙酰半胱氨酸存在于活细胞中，一些Cu(II)配合物可能能够在这些还原剂存在的情况下引发DNA损伤。

The generation of hydroxyl radicals (.OH) from the reaction of Cu(II) complexes with biological reductants such as ascorbic acid, glutathione, acetylcysteine, and hydroquinone was confirmed by spin-trapping experiments using electron spin resonance (ESR). The following Cu(II) complexes were used: Cu(II)-(CyHH)2 (CyHH, cyclo(L-histidyl-L-histidyl)), Cu(II)(OP)2 (OP, o-phenanthroline), Cu(II)(HGG) (HGG, L-histidyl-glycylglycine), and Cu(II)(en)2 (en, ethylenediamine). The methyl radical adduct of alpha-(pyridyl-4-N-oxide)-N-tert-butylnitrone (POBN-CH3) was obtained from the reaction of ascorbic acid with all Cu(II) complexes used here in the presence of a spin trap, POBN, and dimethyl sulfoxide, indicating the generation of .OH. Glutathione, N-acetylcysteine, and hydroquinone reacted with both Cu(II)(CyHH)2 and Cu(II)(OP)2 to generate POBN-CH3, while these reductants did not react with either Cu(II)(HGG) or Cu(II)(en)2. The DNA strand scission caused by reaction mixtures of Cu(II) complexes with reductants was investigated under the same conditions as the ESR spin-trapping experiments. Addition of ascorbic acid to mixtures of these four Cu(II) complexes and DNA resulted in DNA strand breakage. Reaction mixtures of glutathione, N-acetylcysteine, or hydroquinone with Cu(II)-(HGG) or Cu(II)(en)2 did not cause DNA strand scission within the concentration range used. The results obtained here suggest that there is a good correlation between POBN-CH3 formation and DNA strand scission. Thus, DNA strand scission may be caused by .OH generated from the reaction of some Cu(II) complexes with biological reductants under aerobic conditions. Since ascorbic acid, glutathione, and N-acetylcysteine are present in living cells, some Cu(II) complexes may be capable of initiating DNA damage in the presence of these reductants.

来源:Hazardous Substances Data Bank (HSDB)

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被运输到肝脏和肾脏。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、氨基酸结合以及与依赖铜的酶相关联的形式储存，然后分配通过胆汁排出或并入细胞内和细胞外蛋白中。铜通过血浆中与血清白蛋白、铜蓝蛋白或低分子量复合物结合被运输到外周组织。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)

代谢

从Cu(II)配合物与生物还原剂如抗坏血酸、谷胱甘肽、乙酰半胱氨酸和对苯二酚的反应中产生羟基自由基（.OH）已被电子自旋共振（ESR）自旋捕获实验所证实。使用的Cu(II)配合物包括：Cu(II)-(CyHH)2 (CyHH, 环(L-组氨酰-L-组氨酰))，Cu(II)(OP)2 (OP, 邻菲啰啉)，Cu(II)(HGG) (HGG, L-组氨酰-甘氨酰甘氨酸)，和Cu(II)(en)2 (en, 乙二胺)。在自旋捕获剂POBN和二甲亚砜的存在下，抗坏血酸与所有在此使用的Cu(II)配合物反应，产生了alpha-(吡啶-4-N-氧化物)-N-叔丁基氮氧化物（POBN-CH3）的甲基自由基加合物，表明产生了.OH。谷胱甘肽、N-乙酰半胱氨酸和对苯二酚与Cu(II)(CyHH)2和Cu(II)(OP)2反应生成了POBN-CH3，而这些还原剂并没有与Cu(II)(HGG)或Cu(II)(en)2反应。在相同的条件下，研究了Cu(II)配合物与还原剂反应混合物引起的DNA链断裂。将抗坏血酸添加到这四种Cu(II)配合物和DNA的混合物中，导致了DNA链的断裂。在所使用的浓度范围内，谷胱甘肽、N-乙酰半胱氨酸或对苯二酚与Cu(II)-(HGG)或Cu(II)(en)2的反应混合物没有引起DNA链断裂。在这里获得的结果表明，POBN-CH3的形成与DNA链断裂之间存在很好的相关性。因此，DNA链断裂可能是由一些Cu(II)配合物在氧气的条件下与生物还原剂反应产生的.OH引起的。由于抗坏血酸、谷胱甘肽和N-乙酰半胱氨酸存在于活细胞中，一些Cu(II)配合物可能在这些还原剂存在的情况下能够引发DNA损伤。

The generation of hydroxyl radicals (.OH) from the reaction of Cu(II) complexes with biological reductants such as ascorbic acid, glutathione, acetylcysteine, and hydroquinone was confirmed by spin-trapping experiments using electron spin resonance (ESR). The following Cu(II) complexes were used: Cu(II)-(CyHH)2 (CyHH, cyclo(L-histidyl-L-histidyl)), Cu(II)(OP)2 (OP, o-phenanthroline), Cu(II)(HGG) (HGG, L-histidyl-glycylglycine), and Cu(II)(en)2 (en, ethylenediamine). The methyl radical adduct of alpha-(pyridyl-4-N-oxide)-N-tert-butylnitrone (POBN-CH3) was obtained from the reaction of ascorbic acid with all Cu(II) complexes used here in the presence of a spin trap, POBN, and dimethyl sulfoxide, indicating the generation of .OH. Glutathione, N-acetylcysteine, and hydroquinone reacted with both Cu(II)(CyHH)2 and Cu(II)(OP)2 to generate POBN-CH3, while these reductants did not react with either Cu(II)(HGG) or Cu(II)(en)2. The DNA strand scission caused by reaction mixtures of Cu(II) complexes with reductants was investigated under the same conditions as the ESR spin-trapping experiments. Addition of ascorbic acid to mixtures of these four Cu(II) complexes and DNA resulted in DNA strand breakage. Reaction mixtures of glutathione, N-acetylcysteine, or hydroquinone with Cu(II)-(HGG) or Cu(II)(en)2 did not cause DNA strand scission within the concentration range used. The results obtained here suggest that there is a good correlation between POBN-CH3 formation and DNA strand scission. Thus, DNA strand scission may be caused by .OH generated from the reaction of some Cu(II) complexes with biological reductants under aerobic conditions. Since ascorbic acid, glutathione, and N-acetylcysteine are present in living cells, some Cu(II) complexes may be capable of initiating DNA damage in the presence of these reductants.

来源:Hazardous Substances Data Bank (HSDB)

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。铜抑制了诸如葡萄糖-6-磷酸1-脱氢酶、谷胱甘肽还原酶和对氧磷酶等含有巯基团的酶，这些酶保护细胞免受自由氧自由基的侵害。它还影响基因表达，并且是诸如细胞色素C氧化酶和赖氨氧化酶等氧化酶的辅因子。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所致。

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，甚至导致死亡。铜可能引起敏感人群的过敏反应。

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子和喉咙的刺激。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

• 危险等级：
  8
• 包装等级：
  II
• 危险品运输编号：
  UN 1761
• 储存条件：
  库房应保持通风、低温和干燥，并与其他酸类物质分开存放。

制备方法与用途

类别：腐蚀物品
毒性分级：中毒
急性毒性：口服-大鼠 LD50: 750 毫克/公斤
可燃性危险特性：可燃
储运特性：应存放在库房中，保持通风、低温和干燥，并与酸分开存放
灭火剂：水、抗醇泡沫

反应信息

• 作为反应物：
  描述：

  铜-乙二胺络合物 在 双氧水 作用下， 以 not given 为溶剂， 生成 大鼠1,25-二羟基维生素D(1,25(OH)2D)试剂盒
  参考文献：
  名称：

  第一个ESR自旋捕集证据表明水溶液中铜（II）与过氧化氢的反应形成了羟基自由基

  摘要：

  使用水溶性自旋阱5,5-二甲基-1-吡咯啉N通过ESR光谱法确定铜（II）离子与过氧化氢（H 2 O 2）反应过程中羟基自由基（OH·）的形成氧化物（DMPO，1），α-（4-吡啶-1-氧化物）-N-叔丁基亚硝基（POBN，2）和3,5-二溴-4-亚硝基苯磺酸钠（DBNBS，3）。

  DOI：

  10.1039/c39910000330
• 作为产物：
  描述：

  在 H₂O 作用下， 以 水 为溶剂， 生成 铜-乙二胺络合物
  参考文献：
  名称：

  Bernhardt, Paul V.; Comba, Peter; Hambley, Trevor W., Inorganic Chemistry, 1992, vol. 31, # 12, p. 2644 - 2651

  摘要：

  DOI：

文献信息

• Spectroscopic studies on the production of hydroxyl radicals from the reactions of copper(II)polyamine-n-polycarboxylate complexes with hydrogen peroxide
  作者：Toshihiko Ozawa、Akira Hanaki、Kayoko Onodera

  DOI：10.1016/s0277-5387(00)86004-0

  日期：1992.1

  NADH and glutathione, no reaction occurred between CuII(edta) and H2O2; but, in the presence of these biological reductants, CuII(edta) was reduced to CuI and then the subsequent redox reaction (Fenton-type reaction) between CuI and H2O2 occurred to yield hydroxyl radicals (·.OH). From these results, it is concluded that copper(II)-polyamine-N-polycarboxylate complexes cannot directly be reduced to CuI

  光谱研究了铜（II）-多胺-N-多羧酸盐配合物，例如Cu II（edta）（edta：乙二胺四乙酸）和Cu II（dtpa）（dtpa：二亚乙基三胺五乙酸）与过氧化氢（H 2 O 2）的反应。在存在或不存在生物还原剂的情况下。在不存在诸如L-半胱氨酸，N-乙酰基-L-半胱氨酸，L-抗坏血酸，NADH和谷胱甘肽之类的生物还原剂的情况下，Cu II（edta）和H 2 O 2之间没有反应发生。但是，在这些生物还原剂的存在下，Cu II（edta）被还原为Cu I然后发生随后的Cu I和H 2 O 2之间的氧化还原反应（芬顿型反应），产生羟基自由基（·.OH）。从这些结果可以得出结论，H 2 O 2无法将铜（II）-多胺-N-多羧酸盐络合物直接还原为Cu I，因为CU 2 +离子对H 2 O 2的氧化还原电势已被改变。与这些聚胺-N-聚羧酸酯配体连接。
• Assembly of TeO₃^2– Ions Embedded in an Nb/O Cage with Selective Decolorization of Organic Dye
  作者：Zhijie Liang、Junjun Sun、Dongdi Zhang、Pengtao Ma、Chao Zhang、Jingyang Niu、Jingping Wang

  DOI：10.1021/acs.inorgchem.7b00860

  日期：2017.9.5

  A novel 24-niobic-2-tellurite, [H2Te2Nb24O72]14–, was isolated by incorporating tellurite anions into a polyoxoniobate cage. The synthesized cluster represents the first example of a sandwich-type polyoxoniobate with the largest telluroniobate aggregate. Furthermore, the hybrid material acts as an efficient catalyst for the decolorization of basic fuchsin.

  通过将亚碲酸盐阴离子掺入聚氧铌酸盐笼中，分离出一种新型的24-Nio-2--2-碲酸盐[H 2 Te 2 Nb 24 O 72 ] 14–。合成的簇代表具有最大碲酸铌聚集体的夹心型聚氧铌酸盐的第一个实例。此外，杂化材料充当碱性品红的脱色的有效催化剂。
• Gmelin Handbuch der Anorganischen Chemie, Gmelin Handbook: Cu: MVol.B4, 64, page 1581 - 1583
  作者：

  DOI：——

  日期：——
• Kirson, B., Bulletin de la Societe Chimique de France
  作者：Kirson, B.

  DOI：——

  日期：——
• Stepwise Mixed Complex Formation
  作者：William E. Bennett

  DOI：10.1021/ja01563a008

  日期：1957.3