二苯并(a,e)荧蒽 | 5385-75-1

• 物质功能分类: 分析化学 - 标准品 - 挥发性有机化合物(VOCs)
• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 中文名称: 二苯并(a,e)荧蒽
• 中文别名: 二苯并(一,五)荧蒽；二苯(A,E)荧蒽
• 英文名称: dibenzo[a,e]fluoranthene
• 英文别名: Dibenzofluoranthene；dibenz[a.e]aceanthrylene；dibenz[a,e]aceanthrylene；Dibenz[a,e]aceanthrylen；hexacyclo[14.7.1.02,7.08,24.09,14.017,22]tetracosa-1(23),2,4,6,8(24),9,11,13,15,17,19,21-dodecaene
• CAS: 5385-75-1
• 化学式: C₂₄H₁₄
• 分子量: 302.375
• InChiKey: JHOWUOKQHJHGMU-UHFFFAOYSA-N

物化性质

• 熔点：
  232°C
• 沸点：
  378.4°C (rough estimate)
• 密度：
  1.1762 (estimate)
• 物理描述：
  Dibenzo(a,e)fluoranthene appears as yellow crystals. Water insoluble.
• 颜色/状态：
  Yellow needles from benzene
• 溶解度：
  In water, 2.12X10-4 mg/L at 25 °C (est)
• 蒸汽压力：
  7.33X10-11 mm Hg at 25 °C (est)
• 稳定性/保质期：
  - 存在于烟气中。 - 根据IARC致癌性评估，其具有有限的致癌证据，可能引发癌症。
• 保留指数：
  540.77;535.27

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

ADMET

代谢

二苯并[a,e]芘（DBF）在培养的小鼠成纤维细胞中产生DNA-蛋白质交联可能是通过激活DBF的近端代谢物而不是DBF分子本身介导的。为了测试这个假设，测试了几种能增加或减少与交联有关的DBF代谢物产生的试剂。增加培养基中的NADPH浓度能增强交联的产生；1,2-环氧-3,3,3-三氯丙烷（TCPO），一种环氧水解酶的抑制剂，在高浓度时略微减少了DNA-蛋白质交联的形成；诺哈曼（NH），一种抑制DBF代谢某些步骤的抑制剂，完全阻断了交联。讨论了DBF-双二氢二醇，一种在体外识别的双功能代谢物可能的参与。在无DBF的培养基中后培养并没有引起交联的显著减少，这表明修复没有发生。

The production by dibenzo[a,e]fluoranthene (DBF) of DNA-protein cross-links in cultured mouse fibroblasts is probably mediated by the activation of proximate metabolites of DBF and not by the DBF molecule itself. In order to test this hypothesis, several agents that enhance or reduce production of the DBF metabolite putatively involved in cross-linking were tested. Increasing NADPH concentrations in the medium enhanced cross-link production; 1,2-epoxy-3,3,3-trichloropropane (TCPO), an inhibitor of epoxide hydrolases, slightly reduced DNA-protein cross-link formation at high concentrations; norharman (NH), an inhibitor of certain steps in the metabolism of DBF, totally blocked cross-linking. The possible involvement of DBF-bisdihydrodiol, a bifunctional metabolite identified in vitro, is discussed. Postincubation in DBF-free medium did not induce a significant reduction in cross-links, indicating that repair did not take place.

来源:Hazardous Substances Data Bank (HSDB)

代谢

二苯并[a,e]芘、其7-羟基、3,4-和12,13-二氢二醇代谢衍生物以及三种结构相关的合成烃类，对3-甲基胆蒽处理的大鼠和小鼠肝脏线粒体后上清液中的鼠伤寒沙门氏菌TA100株进行了诱变活性测试。在这些化合物中，12,13-二氢二醇显示出最高的活性，比亲本化合物的诱变性高出6-10倍。我们的数据与之前关于二苯并[a,e]芘及其二氢二醇的肝脏微粒体代谢和DNA结合的研究相结合，表明二苯并[a,e]芘向细菌诱变剂的激活可能主要通过相邻的非湾区12,13-二氢二醇环氧化物的形成。

Dibenzo[a,e]fluoranthene, its 7-hydroxy, 3,4- and 12,13-dihydrodiol metabolic derivatives as well as three synthetic, structurally related hydrocarbons, were tested for mutagenicity towards Salmonella typhimurium TA100 strain in the presence of 3-methylcholanthrene-treated rat and mouse liver post-mitochondrial supernatants. Of these compounds, the 12,13-dihydrodiol showed the highest activity, being 6-10 times more mutagenic than the parent compound. Our data, in conjunction with those of previous studies on the liver microsomal metabolism and DNA binding of dibenzo[a,e]fluoranthene and its dihydrodiols, indicate that activation of dibenzo[a,e]fluoranthene to bacterial mutagens may occur predominantly through a vicinal, non-bay-region 12,13-dihydrodiol epoxide.

来源:Hazardous Substances Data Bank (HSDB)

代谢

当二苯并[a,e]芘（DBF）与小鼠肝脏微粒体在牛胸腺DNA存在下体外孵化时，几种代谢物会与DNA共价结合。经过酶促水解后，代谢物-核苷酸加合物的洗脱轮廓显示出六个主要峰，按极性降低的顺序标记为A至F。这与DNA直接与3,4-二羟基-1,2-环氧化-1,2,3,4-四氢DBF（湾区二醇环氧）或12,13-二羟基-10,11-环氧化-10,11,12,13-四氢DBF（伪湾区二醇环氧）反应得到的洗脱轮廓进行了比较。在这两种情况下，加合物的保留时间与主要峰E相同。这两种加合物的荧光光谱与相应的四醇相似。当DNA在微粒体存在下与3,4-二氢二羟基DBF反应时，加合物的洗脱轮廓表明，二氢二醇的邻位环氧化和直接反应是主要的。与12,13-二氢二羟基DBF的代谢反应似乎更为复杂，因为观察到的加合物的数量对应于二氢二醇的邻位环氧化以及在其他位点进一步氧化。

When dibenzo[a,e]fluoranthene (DBF) is incubated in vitro with mouse liver microsomes in the presence of calf thymus DNA, several metabolites bind covalently to DNA. The metabolite-nucleoside adducts were separated by h.p.l.c. after enzymatic hydrolysis. The elution profile of this chromatogram exhibits six main peaks, labeled from A to F in order of decreasing polarity. It was compared to those obtained by direct reaction of DNA with 3,4-dihydroxy-1,2-epoxy 1,2,3,4-tetrahydro DBF (the bay region diol-epoxide) or 12,13-dihydroxy 10,11-epoxy 10,11,12,13-tetrahydro DBF (the pseudo bay region diol-epoxide). In both cases the retention period of the peak of the adduct was identical to that of the main peak E. The fluorescence spectra of these two adducts were similar to those of the corresponding tetrols. When DNA is reacted in the presence of microsomes with 3,4-dihydrodihydroxy DBF, the elution profile of the adducts indicates that vicinal epoxidation of the dihydrodiol and direct reaction is dominant. The metabolic reaction with 12,13-dihydrodihydroxy DBF appears more complex as revealed by the observed number of adducts which correspond to vicinal epoxidation of dihydrodiol as well as further oxidation at other sites.

来源:Hazardous Substances Data Bank (HSDB)

代谢

Norharman（NH）（一种假设的邻二醇环氧化酶抑制剂，在DBF代谢中）对二苯并[a,e]-芘（DBF）的代谢及其在DNA、RNA和蛋白质上的固定的影响已在体外通过与大鼠和小鼠的S-9和微粒体一起孵育进行研究。Norharman（DBF代谢中的一种假设的邻二醇环氧化酶抑制剂）按其浓度成比例地降低微粒体单加氧酶的活性，但对NADPH p450还原酶的活性或环氧化酶的活性没有影响。矛盾的是，在NH存在的情况下，DBF疏水性代谢物的量，特别是二醇和酚的量，在孵化混合物中增加；这种增加与细胞溶胶的结合酶的存在无关。Norharman（DBF代谢中的一种假设的邻二醇环氧化酶抑制剂）不改变DBF在微粒体RNA上的共价结合，相反，它减少了DBF在DNA和孵化混合物蛋白质上的结合。这可以部分解释DBF二醇和酚的增加是通过累积效应。在相同条件下测试的两种高于NH的同系物：苯并[g]-beta咔啉和苯并[i]-beta咔啉，被证明具有抑制作用。

The effects of norharman (NH) (a putative vicinal diolepoxidation inhibitor in DBF metabolism) on the metabolism of dibenzo[a,e]-fluoranthene (DBF) and on its fixation on DNA, RNA and proteins have been studied in vitro by incubation with S-9 and microsomes from rats and mice. Norharman (a putative vicinal diolepoxidation inhibitor in DBF metabolism) causes a decrease of the activity of microsome monooxygenases proportionally to its concentration but has no effect on the activity of NADPH p450 reductase nor on that of epoxide hydrolase. Paradoxically, the amount of DBF hydrophobic metabolites and especially that of diols and phenols, increases in the incubation mixture in the presence of NH; this increase is independent of the presence of conjugation enzymes of cytosol. Norharman (a putative vicinal diolepoxidation inhibitor in DBF metabolism) does not modify the covalent binding of DBF on the microsome RNA, conversely it decreases the binding of DBF on the DNA and on the proteins of the incubation mixture. This could partly explain the increase of DBF diols and phenols by an accumulative effect. Two higher homologs of NH: benzo[g]-beta carboline and benzo[i]-beta carboline, tested under the same conditions, proved inhibitory.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：二苯并(a,e)芘（DB(a,e)F）是一种固体多环芳烃（PAH）。没有这种化合物的商业生产或已知用途。人类暴露和毒性：无可用数据。动物研究：有有限的证据表明DB(a,e)F在实验动物中具有致癌性。二苯并芘-12,13-二氢二醇在Salmonella TA100中的致突变性比二苯并芘-3,4-二氢二醇强六倍。然而，这两种主要的DB(a,e)F近端代谢物，即相应二环氧化的直接前体，在等摩尔基础上表现出几乎相同的启动活性；它们在小鼠皮肤上诱导的乳头状瘤比母体碳氢化合物多三倍。另一方面，DB(a,e)F或两种二苯并芘二氢二醇的上皮瘤启动能力，即进展为恶性肿瘤的乳头状瘤数量，是相当的。这些数据表明，DB(a,e)F激活为细菌致突变物可能主要通过相邻的、非湾区12,13-二氢二醇环氧化的途径。

IDENTIFICATION AND USE: Dibenzo(a,e)fluoranthene (DB(a,e)F) is a solid polycyclic aromatic hydrocarbon (PAH). There is no commercial production or known use of this compound. HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: There is limited evidence in experimental animals for the carcinogenicity of DB(a,e)F. Dibenzofluoranthene-12,13-dihydrodiol is six times more mutagenic in Salmonella TA100 than dibenzofluoranthene-3,4-dihydrodiol. However, these two major DB(a,e)F proximate metabolites, which are immediate precursors of the corresponding diolepoxides, showed on an equimolar basis nearly identical initiation activities on mouse skin; they induced three times more papillomas than the parent hydrocarbon. On the other hand the epithelioma initiation capacities, i.e. the number of papillomas progressing to malignant tumors, of DB(a,e)F or the two dibenzofluoranthene dihydrodiols were equivalent. These data indicate that activation of DB(a,e)F to bacterial mutagens may occur predominantly through a vicinal, non-bay-region 12,13-dihydrodiol epoxide.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

二苯并[a,e]芘对实验动物致癌性的证据有限。总体评估：二苯并[a,e]芘对人类致癌性无法分类（第3组）。

There is limited evidence in experimental animals for the carcinogenicity of dibenzo[a,e]fluoranthene. OVERALL EVALUATION: Dibenzo[a,e]fluoranthene is not classifiable as to its carcinogenicity to humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：二苯并[a,e]芘

IARC Carcinogenic Agent:Dibenzo[a,e]fluoranthene

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第7卷补充：致癌性的总体评估：更新国际癌症研究机构专著第1至42卷，1987年；440页；ISBN 92-832-1411-0（已绝版）

IARC Monographs:Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

来源:International Agency for Research on Cancer (IARC)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36/37
• 危险类别码：
  R40
• WGK Germany：
  3
• 海关编码：
  2902909090

反应信息

• 作为反应物：
  描述：

  二苯并(a,e)荧蒽 在 lead(IV) acetate 作用下， 以 苯 为溶剂， 生成 2-(7-Oxo-7H-benzo[c]fluoren-6-yl)-benzaldehyde
  参考文献：
  名称：

  Oxidation of Dibenzo[a,e]fluoranthene by Osmium Tetroxide

  摘要：

  二苯并[a,e]芴经过四氧化锇处理，考虑化学、理论和物理化学的论据，定义了所得化合物（一种顺式二氢二醇）的性质、结构和构型。

  DOI：

  10.1139/v75-235
• 作为产物：
  描述：

  7-Phenyl-benzanthracen 在 三氯化铝 作用下， 生成 二苯并(a,e)荧蒽
  参考文献：
  名称：

  “二苯并[ a，l ] py”及其已知衍生物的真实性质

  摘要：

  DOI：

  10.1039/c19660000092

文献信息

• Acephenanthrylenes from flash vacuum thermolysis of diarylmethylidenecycloproparenes
  作者：Brian Halton

  DOI：10.1016/j.tetlet.2005.12.047

  日期：2006.2

  Upon flash vacuum thermolysis at 750 °C fluorenylidenecyclopropa[b]naphthalene (1) undergoes opening of the three-membered ring and rearrangement to give a range of C24H14 polycyclic aromatic hydrocarbons. Dibenz[e.l]- and -[e.k]acephenanthrylene (7) and (12), respectively, have been identified while the plausible naphth[1,2-e]- and [2,3-e]acephenanthrylenes (9) and (14) were not detected. With di

  在750℃下的闪蒸真空热解中，亚芴基亚环丙烷[ b ]萘（1）经历三元环的开环并重排，得到一系列C 24 H 14多环芳烃。Dibenz [ e。l ]-和-[ e。已分别鉴定出k ]对苯二甲苯（7）和（12），而未检测到可能的萘[1,2- e ]-和[2,3- e ]对苯二酚（9）和（14）。与二苯基亚甲基环丙烷[ b ]萘（2）环脱氢和重排也提供C 24 H 14多环；dibenz [ e。k ]对苯乙（12）被鉴定和dibenz [ a。e ]乙炔（15）是一种提议的产品。
• Polycyclic fluoranthene hydrocarbons. 2. A new general synthesis
  作者：Bongsup P. Cho、Ronald G. Harvey

  DOI：10.1021/jo00235a005

  日期：1987.12
• Synthesis and conformational analysis of nitropolycyclic fluoranthenes
  作者：Bongsup P. Cho、Misoo Kim、Ronald G. Harvey

  DOI：10.1021/jo00073a045

  日期：1993.10

  Nitroarenes are ubiquitous environmental pollutants some of which exhibit mutagenic and tumorigenic activities. The first systematic investigation of the nitration reactions of the polycyclic fluoranthenes, a major class of nonalternant polyarenes, is described. The specific hydrocarbons studied were benz[e]acephenanthrylene (1), benz[a]aceanthrylene (2), indeno[1,2,3-cd]pyrene (3), indeno[1,2,3-hi]chrysene (4), dibenz[a,e]aceanthrylene (5), dibenz[a,j]aceanthrylene (6), and dibenz[e,k]acephenanthrylene (7). The nitration of all hydrocarbons, except 1, proceeded with remarkable regioselectivity to provide a single mononitro product. In the case of 1, 17 % of a second mononitro isomer was isolated. The structures of the resulting mononitrofluoranthenes (8-15) were fully characterized by analysis of their high-resolution COSY, long-range COSY, and NOESY NMR spectra and by comparison with the spectra of the parent hydrocarbons. The observed nitration sites of the polycyclic fluoranthenes were in excellent agreement with theoretical predictions made by the DEWAR-PI method based on the relative energies of the Wheland intermediates for substitutions at various ring positions. The availability of the complete H-1 chemical shift assignments of the nitropolycyclic fluoranthenes (8-15), together with those of the parent hydrocarbons (1-7) and their UV-visible spectral data, enabled the molecular conformations of the nitro groups to be probed.
• Zander, Chemische Berichte, 1959, vol. 92, p. 2749
  作者：Zander

  DOI：——

  日期：——
• 147. Aromatic hydrocarbons. Part LIX. 1 : 2–3 : 4-Dibenzpyrene
  作者：E. Clar、D. G. Stewart

  DOI：10.1039/jr9510000687

  日期：——

表征谱图