2,3,7-三氯二苯并-对-二恶英 | 33857-28-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶英
• 中文名称: 2,3,7-三氯二苯并-对-二恶英
• 中文别名: 2,3,7-三氯二苯并对二噁英
• 英文名称: 2,3,7-trichlorodibenzodioxin
• 英文别名: 2,3,7-Trichlorodibenzo-p-dioxin；2,3,7-trichloro-dibenzo[1,4]dioxine
• CAS: 33857-28-2
• 化学式: C₁₂H₅Cl₃O₂
• 分子量: 287.53
• InChiKey: ZSIZNEVHVVRPFF-UHFFFAOYSA-N

物化性质

• 熔点：
  162.5°C
• 沸点：
  369.88°C (rough estimate)
• 密度：
  1.5630 (estimate)
• 蒸汽压力：
  9.00e-08 mmHg
• 保留指数：
  2160;2160;2160;2181;2188;2189

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

CDDs通过口服、吸入和皮肤暴露途径被吸收。CDDs通过血清脂质和脂蛋白在血浆中运输，主要分布到肝脏和脂肪组织。CDDs通过微粒体单加氧酶系统非常缓慢地被代谢为极性代谢物，这些代谢物可以与葡萄糖醛酸和谷胱甘肽发生结合反应。它们可能通过诱导I相和II相酶来增加自己的代谢速率。CDDs的主要排泄途径是胆汁和粪便，尽管也有少量通过尿液和哺乳排出。

CDDs are absorbed through oral, inhalation, and dermal routes of exposure. CDDs are carried in the plasma by serum lipids and lipoproteins, distributing mainly to the liver and adipose tissue. CDDs are very slowly metabolized by the microsomal monooxygenase system to polar metabolites that can undergo conjugation with glucuronic acid and glutathione. They may increase the rate of their own metabolism by inducing both phase I and phase II enzymes. The major routes of excretion of CDDs are the bile and the faeces, though smaller amounts are excreted in the urine and via lactation. (L177)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

CDDs通过结合芳基烃受体并随后改变某些基因的转录来产生其毒性作用。对Ah受体的亲和力取决于特定CDD的结构。基因表达的改变可能是由于Ah受体及其异二聚体形成伙伴芳基烃受体核移位子与基因调控元件的直接相互作用，或者启动磷酸化/去磷酸化级联反应，随后激活其他转录因子。受影响的基因包括几个癌基因、生长因子、受体、激素和药物代谢酶。这些基因的转录/翻译改变被认为是CDDs大多数毒性作用的原因。

CDDs cause their toxic effects by binding to the aryl hydrocarbon receptor and subsequently altering the trascription of certain genes. The affinity for the Ah receptor depends on the structure of the specific CDD. The change in gene expression may result from the direct interaction of the Ah receptor and its heterodimer-forming partner, the aryl hydrocarbon receptor nuclear translocator, with gene regulatory elements or the initiation of a phosphorylation/dephosphorylation cascade that subsequently activates other transcription factors. The affected genes include several oncogenes, growth factors, receptors, hormones, and drug-metabolizing enzymes. The change in transcription/translation of these genes is believed to be the cause of most of the toxic effects of CDDs. (L177)

来源:Toxin and Toxin Target Database (T3DB)

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)

毒理性

• 健康影响

暴露于大量氯代二苯并二噁烷（CDDs）会引起氯痤疮，这是一种严重的皮肤疾病，其症状类似于粉刺，主要发生在面部和上半身。CDDs还可能引起肝损伤，并导致长期的葡萄糖代谢改变和激素水平的微妙变化。此外，研究表明CDDs可能会破坏内分泌系统，削弱免疫系统，以及造成生殖损害和出生缺陷、中枢和周围神经系统病理变化、甲状腺疾病、子宫内膜异位症和糖尿病。(L177, L178)

Exposure to large amounts of CDDs causes chloracne, a severe skin disease with acne-like lesions that occur mainly on the face and upper body. CDDs may also cause liver damage and induce long-term alterations in glucose metabolism and subtle changes in hormonal levels. In addition, studies have shown that CDDs may disrupt the endocrine system and weaken the immune system, as well as cause reproductive damage and birth defects, central and peripheral nervous system pathology, thyroid disorders, endometriosis, and diabetes. (L177, L178)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服（L177）；吸入（L177）；皮肤（L177）

Oral (L177) ; inhalation(L177) ; dermal (L177)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

除了氯痤疮，CDD暴露还会导致皮肤疹、色素沉着和体毛过多。

In addition to chloracne, CDD exposure causes skin rashes, discoloration, and excessive body hair. (L177)

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 海关编码：
  2932999060

反应信息

• 作为反应物：
  描述：

  2,3,7-三氯二苯并-对-二恶英 在 镍 硝酸铵 、 一水合肼 、 三乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 硝基甲烷 、 乙醇 、 二氯甲烷 为溶剂， 生成 N-(2-(3,7,8-trichlorodibenzodioxinyl))-2-methacryloyloxybenzamide
  参考文献：
  名称：

  A Novel Approach to the Molecular Imprinting of Polychlorinated Aromatic Compounds

  摘要：

  The aim of this investigation was to determine whether relatively weak interactions, such as hydrogen bonds to aromatic chlorine atoms and interactions involving aromatic pi electrons could be exploited within artificial receptors, constructed using the technique of molecular imprinting. For the purposes of this investigation we chose 2,3,7,8-tetrachlorodibenzodioxin (TCDD)as the model target. Imprinted polymers have been prepared with two new templates designed to create recognition sites for TCDD. The first of these, the bis-N-(4-vinylphenyl)urea derivative of 2,8-dichloro-3,7-diaminodibenzodioxin, employed a carbonyl spacer to introduce aromatic amines into the polymer after reductive cleavage of the template. The second, N-(2-(3,7,8-trichlorodibenzodioxinyl))-2-methacryloyloxybenzamide, incorporated a salicylic acid spacer and introduced a methacrylic acid residue into the polymer following hydrolysis. Both amine and acid groups were positioned in such a way as to interact with TCDD through the formation of weak hydrogen bonds to aromatic chlorine atoms. A second recognition element was introduced into the binding sites by the inclusion of a polymerizable, electron-rich, aromatic ether capable of forming pi-pi interactions with the electron-deficient dioxin molecule. Polymers imprinted with either template showed significantly higher uptake of TCDD than the corresponding nonimprinted controls, even at concentrations as low as 2 nM.

  DOI：

  10.1021/ja9818295
• 作为产物：
  描述：

  硫丙磷 以 氯仿 为溶剂， 生成 2,3,7-三氯二苯并-对-二恶英
  参考文献：
  名称：

  The study on UV-degradation dynamics of 2,3,7,8-tetrachlorodibenza-p-dioxin and its analogues

  摘要：

  A study on UV-degradation dynamics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and its analogues 2,3,7,8-tetrachlorophenoxthin (2,3,7,8-TCPT) and 2,3,7,8-tetrachlorothianthrene(2,3,7,8-TCTR) in solvents CHCl3 and CCl4 was completed. The results indicated that they were degradated by UV in different way in different solvent. The degradation of 2,3,7,8-TCDD and 2,3,7,8-TCPT are pseudo-first-order reactions in CHCl3, but complex reactions in CCl4; the degradation of 2,3,7,8-TCTR is a zero-order reaction in CHCl3, but a pseudo-first-order reaction in CCl4. All of the three compounds disappeared in CCl4 much faster than in CHCl3 under 254 nm UV-irradiation. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0045-6535(96)00150-6

文献信息

• Oxidative destruction of chlorinated persistent organic pollutants by hydroxyl radicals <i>via</i> ozone and UV light irradiation
  作者：Ayyakkannu Ragupathi、Vaibhav Pramod Charpe、Jih Ru Hwu、Kuo Chu Hwang

  DOI：10.1039/d3gc02365f

  日期：——

  several persistent organic pollutants (POPs) by in situ generated hydroxyl radicals using ozone gas and acetonitrile (ACN)–water (2 : 1) as a solvent under ultraviolet light irradiation at room temperature. This method degrades tough and difficult-to-be-oxidized POPs into useful and non-toxic products using ozone gas, which is eco-friendly and helps in remediation of Earth's atmosphere. Besides, we have

  我们开发了一种在室温下使用臭氧气体和乙腈（ACN）-水（2：1）作为溶剂在紫外光照射下原位产生羟基自由基氧化破坏有机氯和几种持久性有机污染物（POP）的方法。该方法利用臭氧气体将难以氧化的持久性有机污染物降解为有用且无毒的产品，既环保又有助于修复地球大气层。此外，我们还推导了几种有机氯化合物和污染物的可能降解机制。总体而言，该方法温和、操作友好、高效、经济可行，可用于降解各种有机氯化合物。
• Monoclonal antibodies reactive with chlorinated dibenzo-p-dioxins and method of preparing and using same
  申请人：WESTINGHOUSE ELECTRIC CORPORATION

  公开号：EP0258006A2

  公开（公告）日：1988-03-02

  Monoclonal antibodies that react with chlorinated dibenzo-p-dioxins, particularly, 2,3,7,8-tetrachlorodi­benzo-p-dioxin. Also a method of producing such antibodies by producing an immunogenic conjugate of a chlorinated dibenzo-p-dioxin and a macromolecule carrier, immunizing an animal with the conjugate, obtaining antibody-producing cells from the animal, fusing the cells with tumor cells to produce hybridomas, selecting from among the hybridomas at least one that produces antibodies reactive with the chlorinated dioxin, and recovering the antibodies. Also analytic, diagnostic, investigational, separatory and other methods of using the antibodies, and compositions con­taining the antibodies for such uses.

  与氯化二苯并-对-二恶英，特别是 2，3，7，8-四氯二苯并-对-二恶英反应的单克隆抗体。 还有一种生产这种抗体的方法，即生产氯化二苯并-对-二恶英和大分子载体的免疫原性共轭物，用共轭物免疫动物，从动物身上获得产生抗体的细胞，将细胞与肿瘤细胞融合产生杂交瘤，从杂交瘤中至少选择一种产生与氯化二恶英反应的抗体，并回收抗体。 还有使用抗体的分析、诊断、研究、分离和其他方法，以及含有这种抗体的组合物。
• Method for the immunoassay of dioxins and dibenzofurans
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP0332819A1

  公开（公告）日：1989-09-20

  A method is described for the use of monoclonal antibodies in a sensitive immunoassay for polyhalogenated polycyclic planar aromatic hydrocarbons such as dioxins and dibenzofurans in industrial samples which contain impurities. Appropriate sample preparation and selective enzyme amplification of the immunoassay sensititvity permits detection of dioxin contaminants in industrial or environmental samples at concentrations in the range of a few parts per trillion.

  本文介绍了一种使用单克隆抗体进行灵敏免疫测定的方法，用于检测含有杂质的工业样品中的多卤代多环平面芳烃，如二恶英和二苯并呋喃。适当的样品制备和免疫测定灵敏度的选择性酶扩增可检测工业或环境样品中浓度为万亿分之几的二恶英污染物。
• DIOXIN DERIVATIVES AND METHOD OF MEASUREMENT THEREWITH
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP1256579A1

  公开（公告）日：2002-11-13

  The invention provides a highly sensitive measurement and detection technique for dioxins, which has advantages inherent to immunoassay; and markers to be used in the technique. Disclosed are a biotinylated dioxin derivative of formula (1): (wherein X represents a hydrogen atom or a chlorine atom; R1 represents a biotin residue; R2's, which may be identical to or different from one another, independently and individually represent an arginine residue or a lysine residue; n is an integer from 1 to 5 inclusive; and m is an integer from 1 to 3 inclusive), and an immunoassay method for dioxins characterized by using the derivatives as a marker.

  本发明提供了一种高灵敏度的二恶英测量和检测技术，该技术具有免疫测定固有的优 点；本发明还提供了用于该技术的标记物。 本发明公开了一种式（1）的生物素化二恶英衍生物： (其中 X 代表氢原子或氯原子；R1 代表生物素残基；R2's（可以彼此相同或不同）独立地和单独地代表精氨酸残基或赖氨酸残基；n 是 1 至 5（包括 5）的整数；m 是 1 至 3（包括 3）的整数），以及一种二恶英的免疫测定方法，其特征是使用该衍生物作为标记物。
• METHOD FOR PREDICTING ACTIVATION ENERGY USING AN ATOMIC FINGERPRINT DESCRIPTOR OR AN ATOMIC DESCRIPTOR
  申请人：Bioinformatics&Molecular Design Research Center

  公开号：EP2354987A2

  公开（公告）日：2011-08-10

  The present invention provides a method for constructing a database of atomic fingerprint descriptors. The invention provides a method for predicting activation energy using an atomic fingerprint descriptor and an atomic descriptor, the method comprising the steps of: (i) calculating the atomic fingerprint descriptor of a substrate; (ii) comparing the calculated atomic fingerprint descriptor with the constructed atomic fingerprint descriptor database to select an atomic position where cytochrome P450-mediated metabolism occurs; and (iii) predicting activation energy for the selected atomic position using an atomic descriptor. Also, the invention provides a method of predicting the activation energy of CYP450-mediated phase I metabolism using effective atomic descriptors. Specifically, the invention provides a method of predicting the activation energy either for cytochrome P450-mediated hydrogen abstraction or for tetrahedral intermediate formation in cytochrome P450-aromatic hydroxylation using equations including effective atomic descriptors. The method of the invention can rapidly predict activation energy for phase I metabolites at a practical level without having to perform a docking experiment between any additional CYP450 and the substrate, or a quantum mechanical calculation, thereby making it easier to develop new drugs using a computer. Also, the present invention may propose a strategy for increasing the bioavailability of drugs through the avoidance of metabolites based on the possibility of drug metabolism. Furthermore, the method of the present invention proposes new empirical approaches which can also be easily applied to activation energies for various chemical reactions, and makes it possible to explain physical and chemical factors that determine activation energy. In addition, through the prediction of activation energy according to the present invention, it is possible to predict i) metabolic products, ii) the relative rate of metabolism, iii) metabolic regioselectivity, iv) metabolic inhibition, v) drug-drug interactions, and vi) the toxicity of a metabolite.

  本发明提供了一种构建原子指纹描述符数据库的方法。本发明提供了一种使用原子指纹描述符和原子描述符预测活化能的方法，该方法包括以下步骤：(i) 计算底物的原子指纹描述符；(ii) 将计算的原子指纹描述符与构建的原子指纹描述符数据库进行比较，以选择细胞色素 P450 介导的代谢发生的原子位置；以及 (iii) 使用原子描述符预测所选原子位置的活化能。此外，本发明还提供了一种利用有效原子描述符预测 CYP450 介导的 I 期代谢活化能的方法。具体来说，本发明提供了一种利用包括有效原子描述符的方程预测细胞色素 P450 介导的氢抽取活化能或细胞色素 P450 芳烃羟化四面体中间体形成活化能的方法。本发明的方法可以在实用水平上快速预测 I 期代谢物的活化能，而无需在任何额外的 CYP450 和底物之间进行对接实验，也无需进行量子力学计算，从而使使用计算机开发新药物变得更加容易。同时，本发明还可以根据药物代谢的可能性，提出一种通过避免代谢物来提高药物生物利用度的策略。此外，本发明的方法提出了新的经验方法，也可以很容易地应用于各种化学反应的活化能，并使解释决定活化能的物理和化学因素成为可能。此外，根据本发明预测活化能，还可以预测 i) 代谢产物；ii) 代谢的相对速率；iii) 代谢的区域选择性；iv) 代谢抑制；v) 药物与药物之间的相互作用；以及 vi) 代谢产物的毒性。