1-(~2~H_5_)苯基(~2~H_6_)丙烷-2-胺 | 82019-04-3

• 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: 1-(~2~H_5_)苯基(~2~H_6_)丙烷-2-胺
• 英文名称: 2-hydroxy-3,7,8-trichlorodibenzo-4-dioxin
• 英文别名: 7-Hydroxy-2,3,8-trichlorodibenzo-p-dioxin；3,7,8-Trichlorooxanthren-2-ol；3,7,8-trichlorodibenzo-p-dioxin-2-ol
• CAS: 82019-04-3
• 化学式: C₁₂H₅Cl₃O₃
• 分子量: 303.529
• InChiKey: PMDIZNYHSROIKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  18
• 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：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

8-羟基-2,3,7-三氯代二苯并-p-二恶英已知的人类代谢物包括(2S,3S,4S,5R)-3,4,5-三羟基-6-(3,7,8-三氯代二苯并-p-二恶英-2-基)氧基氧杂环己烷-2-羧酸。

8-Hydroxy-2,3,7-TriCDD has known human metabolites that include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-(3,7,8-trichlorodibenzo-p-dioxin-2-yl)oxyoxane-2-carboxylic acid.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  1-(~2~H_5_)苯基(~2~H_6_)丙烷-2-胺 在 sodium hydroxide 、 甲基三辛基氯化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 6-(3,7,8-Trichlorodibenzo-p-dioxin-2-yl)oxyhexanoic acid
  参考文献：
  名称：

  Hapten Synthesis and Antibody Development for Polychlorinated Dibenzo-p-dioxin Immunoassays

  摘要：

  This paper reports the synthesis of haptens and the generation and preliminary evaluation of polyclonal antibodies for the detection of dioxins such as TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) by ELISA (enzyme-linked immunosorbent assay). These novel haptens contain unsaturation between the halogenated dibenzo-p-dioxin ring system and the protein to which it is conjugated, presenting a rigid handle structure. The substitution pattern is identical with or similar to that of TCDD (i.e., 2,3,7,8- or 1,2,3,7,8-). Finally, the haptens lack polar groups for hydrogen bonding. In direct binding assays using the new polyclonal antibodies there was excellent recognition of hapten-protein conjugates, including recognition of those hapten conjugates that were not used as immunogens (i.e., assay systems heterologous in hapten structure). These haptens do elicit selective immune responses in rabbits. Their evaluation in an ELISA format demonstrated the usefulness of these haptens for the detection of dioxins. An IC50 of 0.8 ng/well (16 ng/mL) was observed for an unoptimized system that used 2,3,7-trichloro-8-methyldibenzo-p-dioxin as an analytical surrogate standard.

  DOI：

  10.1021/jf970716m
• 作为产物：
  描述：

  2,3,7-三氯二苯并-对-二恶英 在 yeast microsomes containing human cytochrome P₄₅₀ 1A₁ 作用下， 以 phosphate buffer 为溶剂， 生成 1-(~2~H_5_)苯基(~2~H_6_)丙烷-2-胺
  参考文献：
  名称：

  Metabolism of Polychlorinated Dibenzo-p-dioxins (PCDDs) by Human Cytochrome P450-Dependent Monooxygenase Systems

  摘要：

  Metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) by monooxygenase systems dependent on 12 forms of human cytochrome P450 (CYP) was examined with the recombinant yeast microsomes containing each of the human CYP. The metabolites of PCDDs were analyzed by HPLC and GCMS. Remarkable metabolism by the multiple CYP forms was observed toward dibenzo-p-dioxin (IDD) and mono-, di-, and trichloroDDs. The metabolism contained multiple reactions such as hydroxylation at an unsubstituted position, hydroxylation with migration of a chloride substituent, and hydroxylation with elimination of a chloride substituent. Although major CYPs in human liver such as CYP2C8, CYP2C9, and CYP3A4 showed no significant metabolism toward the PCDDs, CYP1A1 and CYP1A2 showed high catalytic activity toward DD and mono-, di-, and trichloroDDs. The kinetic parameters K-m(app) and V-max of the CYP1A1-dependent 8-hydroxylation activity of 2,3,7-trichloro-DD (2,3,7-triCDD) were estimated to be 0.30 muM and 51 (mol/min/mol of P450), respectively, suggesting that 2,3,7-triCDD was a good substrate for CYP1A1. However, none of the CYPs showed any detectable activity [<0.01 mol/min/mol of P450)] toward 2,3,7,8-tetraCDD. Substrate-induced absorption spectrum and inhibition studies indicated that CYP1A1 could bind 2,3,7,8-tetraCDD with considerably high affinity. It was strongly suggested that the long half-life (7.1 years) of 2,3,7,8-tetraCDD in humans was due to an extremely low activity of CYPs toward 2,3,7,8-tetraCDD in addition to its chemical stability.

  DOI：

  10.1021/jf020415z

文献信息

• 一种二噁英抗体及其制备方法与应用
  申请人：中国农业科学院农业质量标准与检测技术研究所

  公开号：CN111718321A

  公开（公告）日：2020-09-29

  本发明公开了一种二噁英抗体及其制备方法与应用。本发明基于免疫学原理，设计、合成小分子半抗原，与载体蛋白偶联，制备有效人工抗原，通过免疫动物制备针对二噁英类小分子化合物的高特异性和高亲和力抗体。利用抗原抗体的特异性免疫反应和易被检测识别的标记物的放大作用，定量的检测样本中痕量二噁英类小分子目标分析物，具有特异性好、灵敏度高、准确、快速、方便、廉价等特点。
• Synthesis of oxygenated derivatives of 2,3,7,8-tetrachlorodibenzo-p-dioxin
  作者：Sudhir K. Singh、Subodh. Kumar

  DOI：10.1021/jf00033a030

  日期：1993.9.1

  Four monomethoxy, five dimethoxy and four dihydroxy derivatives of polychlorodibenzo-p-dioxin been synthesized, and their physical and spectral properties (NMR and MS) have been reported. The general method for the synthesis of specific mono- and dimethoxy derivatives in reasonable yields has been found to be the condensation of 4,5-dichlorocatechol with appropriately substituted o-chloro-nitrobenzenes. The monomethoxy derivatives thus prepared were demethylated by boron tribromide-dimethyl sulfide. Several mono- and dihydroxypolychlorodibenzo-p-dioxins have been identified as metabolites of the highly toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, most of these metabolites have not been fully characterized due to the lack of appropriate standards. The availability of these synthetic oxygenated derivatives of TCDD can be used to establish the structure and the potential toxicity associated with these metabolites.
• MASON G.; SAFE S., CHEMOSPHERE, 15,(1986) N 9-12, 2081-2083
  作者：MASON G.、 SAFE S.

  DOI：——

  日期：——
• Metabolism of Polychlorinated Dibenzo-<i>p</i>-dioxins (PCDDs) by Human Cytochrome P450-Dependent Monooxygenase Systems
  作者：Kuniyo Inouye、Raku Shinkyo、Teisuke Takita、Miho Ohta、Toshiyuki Sakaki

  DOI：10.1021/jf020415z

  日期：2002.9.1

  Metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) by monooxygenase systems dependent on 12 forms of human cytochrome P450 (CYP) was examined with the recombinant yeast microsomes containing each of the human CYP. The metabolites of PCDDs were analyzed by HPLC and GCMS. Remarkable metabolism by the multiple CYP forms was observed toward dibenzo-p-dioxin (IDD) and mono-, di-, and trichloroDDs. The metabolism contained multiple reactions such as hydroxylation at an unsubstituted position, hydroxylation with migration of a chloride substituent, and hydroxylation with elimination of a chloride substituent. Although major CYPs in human liver such as CYP2C8, CYP2C9, and CYP3A4 showed no significant metabolism toward the PCDDs, CYP1A1 and CYP1A2 showed high catalytic activity toward DD and mono-, di-, and trichloroDDs. The kinetic parameters K-m(app) and V-max of the CYP1A1-dependent 8-hydroxylation activity of 2,3,7-trichloro-DD (2,3,7-triCDD) were estimated to be 0.30 muM and 51 (mol/min/mol of P450), respectively, suggesting that 2,3,7-triCDD was a good substrate for CYP1A1. However, none of the CYPs showed any detectable activity [<0.01 mol/min/mol of P450)] toward 2,3,7,8-tetraCDD. Substrate-induced absorption spectrum and inhibition studies indicated that CYP1A1 could bind 2,3,7,8-tetraCDD with considerably high affinity. It was strongly suggested that the long half-life (7.1 years) of 2,3,7,8-tetraCDD in humans was due to an extremely low activity of CYPs toward 2,3,7,8-tetraCDD in addition to its chemical stability.
• Hapten Synthesis and Antibody Development for Polychlorinated Dibenzo-<i>p</i>-dioxin Immunoassays
  作者：James R. Sanborn、Shirley J. Gee、S. Douglass Gilman、Yukio Sugawara、A. Daniel Jones、Jane Rogers、Ferenc Szurdoki、Larry H. Stanker、Donald W. Stoutamire、Bruce D. Hammock

  DOI：10.1021/jf970716m

  日期：1998.6.1

  This paper reports the synthesis of haptens and the generation and preliminary evaluation of polyclonal antibodies for the detection of dioxins such as TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) by ELISA (enzyme-linked immunosorbent assay). These novel haptens contain unsaturation between the halogenated dibenzo-p-dioxin ring system and the protein to which it is conjugated, presenting a rigid handle structure. The substitution pattern is identical with or similar to that of TCDD (i.e., 2,3,7,8- or 1,2,3,7,8-). Finally, the haptens lack polar groups for hydrogen bonding. In direct binding assays using the new polyclonal antibodies there was excellent recognition of hapten-protein conjugates, including recognition of those hapten conjugates that were not used as immunogens (i.e., assay systems heterologous in hapten structure). These haptens do elicit selective immune responses in rabbits. Their evaluation in an ELISA format demonstrated the usefulness of these haptens for the detection of dioxins. An IC50 of 0.8 ng/well (16 ng/mL) was observed for an unoptimized system that used 2,3,7-trichloro-8-methyldibenzo-p-dioxin as an analytical surrogate standard.