1-硝基芘 | 5522-43-0

• 物质功能分类: 化学试剂 - 有机试剂 - 硝基化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 中文名称: 1-硝基芘
• 中文别名: 1-硝基比
• 英文名称: 1-nitropyrene
• 英文别名: 1-nitropyrenene
• CAS: 5522-43-0；63021-86-3
• 化学式: C₁₆H₉NO₂
• mdl: MFCD00004138
• 分子量: 247.253
• InChiKey: ALRLPDGCPYIVHP-UHFFFAOYSA-N

物化性质

• 熔点：
  153-155 °C (lit.)
• 沸点：
  390.29°C (rough estimate)
• 密度：
  1.1699 (rough estimate)
• 溶解度：
  可溶于氯仿（少量，加热），乙酸乙酯（轻微，加热）
• 颜色/状态：
  Yellow needles or prisms from ethanol
• 稳定性/保质期：
  Photodecomposition to 2-propanol is readily induced by ultra-violet/ visible light.
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
• 保留指数：
  425.5

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

几种来自动物和人类的细菌及肠道微生物菌株已被证明可以减少1-硝基芘。在某些情况下，这种代谢伴随着一种DNA加合物的形成，被鉴定为N-(脱氧鸟苷-8-yl)-l-氨基芘。

Several strains of bacterial & gut microflora from animals & humans have been shown to reduce 1-nitropyrene. In some instances, this metab was accompanied by the formation of a DNA adduct identified as N-(deoxyguanosin-8-yl)-l-aminopyrene.

来源:Hazardous Substances Data Bank (HSDB)

代谢

新生小鼠比老年小鼠更有效地代谢1-硝基芘；主要的代谢物是酚和二氢二醇。

... Newborn mice metabolized 1-nitropyrene more efficiently than older mice; the predominant metabolites were phenols & dihydrodiols.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在隔离灌注并通气的鼠肺中，[14C]1-硝基芘的主要代谢物是3-、6-和8-羟基-1-硝基芘；也检测到较小量的1-羟基-1-硝基芘、1-氨基芘和N-乙酰-1-氨基芘。用3-甲基胆烷预处理可以使代谢速率增加十倍，与组织大分子相关的放射性活性增加二十倍。用柴油尾气（颗粒物，7.4毫克/立方米）预处理大鼠4周，可以使灌注肺和鼻腔组织的代谢速率增加两倍，与灌注肺组织大分子相关的放射性活性增加四倍。在隔离灌注的大鼠肝脏中，N-乙酰-1-氨基芘是(14)C 1-硝基芘的主要代谢物；检测到较小量的1-氨基芘和羟基-1-硝基芘。

In isolated perfused & ventilated rat lungs, the major metabolites of [14C]1-nitropyrene were 3-, 6-, & 8- hydroxy l-nitropyrene; smaller quantities of 1-hydroxy-l-nitropyrene, 1-aminopyrene & N-acetyl-l-aminopyrene were also detected. Pretreatment with 3-methylcholanthrene increased the rate of metab ten fold & the extent of radioactivity associated with tissue macromolecules 20 fold. Pretreatment of rats with diesel exhaust (particles, 7.4 Mg/ M3) for 4 wk increased the rate of metab in perfused lung & in nasal tissue two fold & the extent of radioactivity associated with tissue macromolecules in the perfused lung four fold. In isolated perfused rat livers, N-acetyl-l-aminopyrene was the major metabolite of (14)C 1-nitropyrene; smaller quantities of 1-aminopyrene & hydroxy-l-nitropyrenes were detected.

来源:Hazardous Substances Data Bank (HSDB)

代谢

中国仓鼠卵巢细胞、中国仓鼠肺成纤维细胞、小牛胸腺细胞、兔肺泡巨噬细胞、兔上皮细胞和人二倍体成纤维细胞催化1-硝基芘还原为一个中间体，该中间体与DNA结合，形成一种加合物，被鉴定为N-(脱氧鸟苷-8-基)-l-氨基芘。将兔肺和气管组织与[14C]1-硝基芘一起培养，导致放射性物质与细胞DNA结合。大鼠原代肝细胞、中国仓鼠V79细胞和人肝癌HepG2细胞催化1-硝基芘转化为1-氨基芘。后者细胞系中还检测到了氧化代谢物。来自大鼠、兔和狗肝脏的胞质制剂催化1-硝基芘还原为1-氨基芘。大鼠肝脏、肺和鼻组织的线粒体后上清液以及兔和仓鼠的肺和肝脏上清液催化1-硝基芘的氧化和还原。豚鼠肝脏微体也催化1-硝基芘的氧化。在某些情况下，这种代谢伴随着与外源DNA的结合。在37°C下将[3H]1-硝基芘与牛胸腺DNA、牛黄嘌呤氧化酶和次黄嘌呤一起培养后，显示与DNA的共价结合与还原酶的量成正比。

Chinese hamster ovary cells, Chinese hamster lung fibroblasts, calf thymus cells, rabbit alveolar macrophages, rabbit epithelial cells & human diploid fibroblasts catalysed the reduction of 1-nitropyrene to an intermediate which bound to DNA, giving an adduct identified as N-(deoxyguanosin-8-yl)-l-aminopyrene. Incubation of rabbit lung & tracheal tissues with [14C]1-nitropyrene resulted in association of the radioactivity with cellular DNA. Primary rat hepatocytes, Chinese hamster V79 cells & human hepatoma HepG2 cells catalysed the conversion of 1-nitropyrene into 1-aminopyrene. Oxidized metabolites were also detected with the latter cell line. Cytosolic preparations from the livers of rats, rabbits, & dogs catalysed the reduction of 1-nitropyrene to 1-aminopyrene. Postmitochondrial supernatants of rat liver, lung & nasal tissue & of rabbit & hamster lung & liver catalysed both the oxidation & reduction of 1-nitropyrene. Guinea-pig liver microsomes also catalysed the oxidation of 1-nitropyrene. In some instances, this metab was accompanied by binding to exogenous DNA. Following incubation of [3H]1-nitropyrene with calf thymus DNA, bovine xanthine oxidase & hypoxanthine at 37 °C, covalent binding to DNA was shown to be proportional to the amount of reducing enzyme present.

来源:Hazardous Substances Data Bank (HSDB)

代谢

1-硝基芘在人体内已知的代谢物包括3-羟基-1-硝基芘、4,5-二氢-4,5-环氧-1-硝基芘、6-羟基-1-硝基芘和8-羟基-1-硝基芘。

1-nitropyrene has known human metabolites that include 3-hydroxy-1-nitropyrene, 4,5-Dihydro-4,5-epoxy-1-nitropyrene, 6-hydroxy-1-nitropyrene, and 8-hydroxy-1-nitropyrene.

来源:NORMAN Suspect List Exchange

毒理性

• 致癌性证据

致癌性分类：1）人类中无数据；2）动物中有证据：证据充分。对人类致癌风险的总体评估为2B组：该物质可能对人类致癌。

Classification of carcinogenicity: 1) no data available in humans; 2) evidence in animals: sufficient evidence. Overall summary evaluation of carcinogenic risk to humans is Group 2B: The agent is possibly carcinogenic to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

1-硝基芘：合理预期为人类致癌物。/硝基芳烃（选定）：1-硝基芘/

1-Nitropyrene: reasonably anticipated to be a human carcinogen. /Nitroarenes (Selected): 1-Nitropyrene/

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：1-硝基芘

IARC Carcinogenic Agent:1-Nitropyrene

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：2A组：可能对人类致癌

IARC Carcinogenic Classes:Group 2A: Probably carcinogenic 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） 第46卷：（1989年）柴油和汽油发动机排气及一些硝基芳烃 第105卷：（2013年）柴油和汽油发动机排气及一些硝基芳烃

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) Volume 46: (1989) Diesel and Gasoline Engine Exhausts and Some Nitroarenes Volume 105: (2013) Diesel and Gasoline Engine Exhausts and Some Nitroarenes

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

费舍尔344大鼠分组通过鼻吸方式暴露于[3H]1-硝基芘，要么作为涂层（约占质量的6%）在相对不溶性、超细的67镓氧化物颗粒（6.2 mg/立方米）上，要么作为均匀的超细气溶胶（43微克/立方米）。暴露于颗粒上的1-硝基芘的大鼠通过粪便排出了大部分沉积的放射性物质（75 + 或 -18%），而暴露于1-硝基芘气溶胶的大鼠通过尿液排出了大部分放射性标记（76 + 或 - 18%）。两组之间1-硝基芘的肺清除率没有差异。大部分气溶胶通过直接吸收进入血液从呼吸道清除，而与颗粒相关的硝基芘通过血液吸收和粘膜清除随后通过吞咽和粪便排出体外。

Groups of Fischer 344 rats were exposed to [3H]1-nitropyrene by nose only inhalation, either as a coating (about 6% by mass) on relatively insoluble, ultrafine 67gallium oxide particles (6.2 mg/cu m) or as a homogeneous ultrafine aerosol (43 ug/cu m). Rats exposed to 1-nitropyrene on particles excreted the majority of the deposited radioactivity in the feces (75 + or -18%), whereas animals exposed to 1-nitropyrene aerosol excreted a major portion of the radiolabel in the urine (76 + or - 18%). There was no difference in the rates of lung clearance of 1-nitropyrene between the two groups. Most of the aerosol was cleared from the respiratory tract by direct absorption into the blood, while particle associated nitropyrene was cleared by both blood absorption & mucociliary clearance followed by ingestion & fecal excretion.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雄性Fischer 344大鼠通过鼻腔吸入暴露于不同浓度的[14C]1-硝基芘和[14C]1-硝基芘涂覆在柴油排气颗粒上（50-1100微克/立方米1-硝基芘；颗粒物浓度，70-7200微克/立方米）。在所测试的浓度范围内，[14C]1-硝基芘通过尿液和粪便的排泄途径与硝基芘的浓度无关，无论是单独给予还是与柴油排气颗粒相关。在所有情况下，粪便排泄是主要的消除途径，通过这条途径排泄的量是通过尿液的约两倍。呼吸道中[14C]1-硝基芘的分数沉积似乎并不依赖于浓度。尿液和粪便中(14)C的消除半衰期约为15-20小时。暴露于涂覆在柴油排气颗粒上的[14C]1-硝基芘的大鼠肺含有的(14)C几乎是没有暴露于(14C)-1-硝基芘单独的大鼠肺的5倍，暴露后1小时内。这种差异在暴露后94小时增加到80倍。暴露于涂覆柴油颗粒的大鼠肺中(14)C清除的长期半衰期为36天，而单独暴露于1-硝基芘后的半衰期仅为两天。同样的1-硝基芘制剂的胃肠道吸收在口服剂量为10微克/千克体重后进行了研究。1小时内，>90%的(14)C被发现在硝基芘代谢物中。在雄性Sprague Dawley大鼠通过气管内滴注[14C]1-硝基芘（8纳米摩尔[2微克]）涂覆在柴油颗粒上（剂量，20毫克/千克体重）、与未标记的柴油颗粒一起滴注或单独给药后，以及腹腔注射(14)C-1-硝基芘单独后，14C的总体排泄模式相似，并且与吸入后的肺部保留也相似。在处理过的肺部已经观察到与蛋白质相关的放射性，但在给药后24小时内没有检测到DNA加合物的水平。

Male Fischer 344 rats were exposed by nose only inhalation to various concns of [14C]1-nitropyrene & [14C]1-nitropyrene coated on diesel exhaust particles (50-1100 ug/cu m 1-nitropyrene; particulate concn, 70-7200 ug/cu m). Over the range of concns tested, the pathways for excretion of [14C]1-nitropyrene in urine & feces were independent of the concn of nitropyrene, whether given alone or associated with diesel exhaust particles. In all cases, fecal excretion was the major route of elimination, about twice as much being excreted by this route as in the urine. The fractional deposition of [14C]1-nitropyrene in the respiratory tract did not appear to be dependent on the concn. Half times for elimination of (14)C in urine & feces were about 15-20 hr. Lungs of rats exposed to [14C]1-nitropyrene coated on diesel exhaust particles contained nearly 5 times more (14)C than lungs from rats exposed to (14C)-1-nitropyrene alone within 1 hr after exposure. This difference was increased to 80 fold at 94 hr after exposure. The long term half time for clearance of (14)C in the lungs of rats exposed to coated diesel particles was 36 days, in contrast to two days after exposure to 1-nitropyrene alone. The GI absorption of the same 1-nitropyrene preparations was studied after an oral dose of 10 ug/kg bw. Within 1 hr, >90% of (14)C was found in nitropyrene metabolites. The overall excretion pattern of 14C was similar after intratracheal instillation of male Sprague Dawley rats with [14C]1-nitropyrene (8 nmol [2 ug]) either coated onto diesel particles (dose, 20 mg/kg bw), instilled along with unlabelled diesel particles, or administered alone, & was also similar to that seen after ip injection of (14)C-1-nitropyrene alone. Lung retention was also similar to that following inhalation ... . Protein associated radioactivity has been observed in particle treated lungs, with no detectable level of DNA adducts found up to 24 hr after admin.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  T
• 危险等级：
  IRRITANT
• 危险品标志：
  Xn
• 安全说明：
  S22,S36/37,S36/37/39,S45
• 危险类别码：
  R20/21/22,R40
• WGK Germany：
  3
• 海关编码：
  2904209090
• RTECS号：
  UR2480000

反应信息

• 作为反应物：
  描述：

  1-硝基芘 在 sodium hydrogen sulfide 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 N-甲基-1-芘胺
  参考文献：
  名称：

  RNA修饰的尿苷衍生物作为RNA中潜在的电子供体的制备和表征

  摘要：

  大约20年前首次观察到跨双链DNA的电荷转移，并且此后一直是大量研究的主题。在这方面几乎没有研究过RNA，这至少是由于缺乏适当功能化的核糖核苷酸结构单元以在掺入寡核糖核苷酸中时用作电子源。我们合成了两个带有核碱基C5的py或二甲基氨基py的尿苷衍生物。成功合成的关键是使Suzuki–Miyaura条件适应to部分与核糖核苷的偶联。与标准的5'-的pyrenylated核苷的最终装饰Ø和2'- - Ø保护基团和随后的3' Ø-磷酸化作用为整合入RNA奠定了基础。两种吡啶基化尿苷和相应修饰的寡核苷酸的光谱分析表明，特别是二甲氨基amino官能化的核苷是一种有前途的候选物，可作为RNA电荷转运研究的电子源。

  DOI：

  10.1039/c8ob02246a
• 作为产物：
  描述：

  芘 在 ammonium persulfate 、 sodium nitrite 作用下， 以 乙腈 为溶剂， 反应 21.0h， 以98%的产率得到1-硝基芘
  参考文献：
  名称：

  一硝基py的光谱和光化学性质

  摘要：

  通过比较三种单硝基py的光谱和光化学性质，研究了硝基对pyr芳族π系统的影响。1-和4-硝基py的紫外光谱和质谱图显示硝基芳族化合物的相互作用是正常的，而对于2-硝基py则没有观察到。缺乏相互作用的现象反映在与pyr非常相似的紫外光谱和M-NO丰度非常低的质谱中。三种化合物的光化学行为取决于相互作用的程度。1-硝基trop显示亚硝酸根重排导致1-羟基py（88％）和1-羟基-2-硝基py（7％）。4-硝基py的光产物为pyr（9％）和与溶剂反应的不稳定产物。由于缺乏相互作用，2-硝基trop在光化学条件下非常稳定。类似地，位阻的1-甲基-2-硝基py也对光非常稳定。发现对于硝基-芳族化合物观察到的光化学硝基-亚硝酸盐重排受电子效应支配。

  DOI：

  10.1002/recl.19871060403
• 作为试剂：
  描述：

  1-氨基芘 、 甘油 在 1-硝基芘 、 硫酸 作用下， 生成 -氮杂苯并(a)芘
  参考文献：
  名称：

  Vollmann et al., Justus Liebigs Annalen der Chemie, 1937, vol. 531, p. 1,131

  摘要：

  DOI：

文献信息

• Selective Nitration of Aromatic Compounds with Bismuth Subnitrate and Thionyl Chloride
  作者：Hussni Muathen

  DOI：10.3390/80700593

  日期：——

  Bismuth subnitrate/thionyl chloride have been found to be an efficient combination of reagents for nitration of a wide range of aromatic compounds in dichloromethane. Phenols, in particular, were easily mononitrated and dinitrated with the reagents by controlling the stoichiometry,

  已发现碱式硝酸铋/亚硫酰氯是一种有效的试剂组合，可用于在二氯甲烷中硝化多种芳香族化合物。尤其是酚类，通过控制化学计量，很容易与试剂一起单硝化和二硝化，
• A New Class of Heterogeneous Platinum Catalysts for the Chemoselective Hydrogenation of Nitroarenes
  作者：Valerica Pandarus、Rosaria Ciriminna、François Béland、Mario Pagliaro

  DOI：10.1002/adsc.201000945

  日期：2011.5

  A new series of nanostructured platinum catalysts able to catalyze the selective reduction of nitroarenes has been developed. The materials, made of organosilica physically doped with nanostructured platinum(0), are stable and efficient. Reactions in general proceed with high yield and often go to completion, while the catalysts can be reused in further reaction runs. This establishes a new class of

  已经开发了一系列能够催化硝基芳烃选择性还原的纳米结构铂催化剂。该材料由物理掺杂有纳米结构的Platinum（0）的有机二氧化硅制成，稳定且高效。通常，反应以高收率进行并且经常完成，而催化剂可以在以后的反应运行中重复使用。这为合成有机化学建立了新的一类相关的固体催化剂，称为Silia Cat铂水凝胶。
• Palladium-catalyzed denitrative Sonogashira-type cross-coupling of nitrobenzenes with terminal alkynes
  作者：Boya Feng、Yudong Yang、Jingsong You

  DOI：10.1039/c9cc08663c

  日期：——

  Described herein is a palladium-catalyzed cross-coupling reaction between nitroarenes and terminal alkynes, offering a facile method for C(sp2)-C(sp) bond formation. The utility of this protocol has been proven by the construction of polycyclic aromatic hydrocarbons (PAHs) and orthogonal cross-coupling.

  本文描述的是硝基芳烃与末端炔烃之间的钯催化交叉偶联反应，为形成C（sp2）-C（sp）键提供了一种简便的方法。该协议的实用性已通过多环芳烃（PAH）的构建和正交交叉偶联得到了证明。
• Interactions of New Synthesized Fluorescent Cationic Amphiphiles Bearing Pyrene Hydrophobe with Plasmid DNA: Binding Affinities, Aggregation and Intracellular Uptake
  作者：Ruilong Sheng、Ting Luo、Yingdan Zhu、Hui Li、Amin Cao

  DOI：10.1002/mabi.201000047

  日期：2010.8.11

  we prepared a novel series of cationic amphiphiles denoted as the Py‐cations (Py‐Gly, Py‐Ala, Py‐Cap, Py‐G1‐Lys and Py‐G2‐Lys) bearing fluorescent pyrene and various hydrocarbon linkers between the pyrene hydrophobe and cationic block. Employing these new cationic amphiphiles with pyrene as the fluorescent probe, the interactions between these Py‐cations and plasmid DNA (pDNA) in distilled water and

  在这项工作中，我们制备了一系列新颖的阳离子两亲物，它们被称为Py阳离子（Py-Gly，Py-Ala，Py-Cap，Py-G 1 -Lys和Py-G 2 -Lys），带有荧光pyr和各种hydro疏水基与阳离子嵌段之间的烃连接基。使用这些新的阳离子两亲物，以pyr作为荧光探针，在蒸馏水和0.1 M溶液中这些Py阳离子与质粒DNA（p DNA） 之间的相互作用PBS缓冲溶液已经通过紫外可见光谱仪和荧光光谱仪进行了探索，还使用了溴化乙锭染料置换和琼脂糖凝胶阻滞剂分析来评估其在水溶液中的pDNA结合亲和力。此外，通过动态激光散射（DLS）和原子力显微镜（AFM）检查了自组装Py-阳离子/ pDNA脂质复合物聚集体的平均大小和形态。发现这些荧光阳离子两亲物 在蒸馏水中的λ = 340 nm处显示of探针的蓝色荧光发射，而它们与pDNA的相互作用导致在λ处出现新的强绿色发射 = 490 nm，这可能是
• STIMULI-SWITCHABLE MOIETIES, MONOMERS AND POLYMERS INCORPORATING STIMULI-SWITCHABLE MOIETIES, AND METHODS OF MAKING AND USING SAME
  申请人：THE GOVERNORS OF THE UNIVERSITY OF ALBERTA

  公开号：US20170267689A1

  公开（公告）日：2017-09-21

  Stimuli-switchable moieties, monomers incorporating stimuli-switchable moieties, and polymers incorporating such stimuli-switchable moieties are provided. The stimuli-switchable moiety can be a pyrano aryl chromenone-derivative. The stimuli-switchable monomer can be a lactone monomer. The stimuli-switchable monomer can be an amino acid, which can be incorporated into a specific peptide sequence by peptide synthesis.

  提供刺激响应性基团、包含刺激响应性基团的单体以及包含此类刺激响应性基团的聚合物。刺激响应性基团可以是吡喃并芳基色烯酮衍生物。刺激响应性单体可以是内酯单体。刺激响应性单体可以是氨基酸，其可以通过肽合成并入特定的肽序列中。

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