chromium(VI) oxide

• 分子结构分类: 无机化合物 - 混合金属/非金属化合物 - 过渡金属有机体
• 英文名称: chromium(VI) oxide
• 英文别名: CrO3；chromium trioxide；chromium oxide；chromic anhydride；Jones' reagent；Collins reagent；Chromium hydroxide hydrate；chromium;trihydrate
• 化学式: CrO₃
• 分子量: 99.9942
• InChiKey: LXMQZGGLHVSEBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.48
• 重原子数：
  4
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  3
• 氢给体数：
  3
• 氢受体数：
  3

ADMET

代谢

铬通过口服、吸入或皮肤接触被吸收，并分布到几乎所有组织中，肾脏和肝脏中的浓度最高。骨骼也是一个主要的储存场所，并可能导致长期保留。六价铬与硫酸盐和铬酸盐的相似性使其能够通过硫酸盐转运机制进入细胞。在细胞内，六价铬首先被还原为五价铬，然后通过许多物质，包括抗坏血酸、谷胱甘肽和烟酸腺嘌呤二核苷酸，被还原为三价铬。铬几乎全部通过尿液排出体外。(A12, L16)

Chromium is absorbed from oral, inhalation, or dermal exposure and distributes to nearly all tissues, with the highest concentrations found in kidney and liver. Bone is also a major storage site and may contribute to long-term retention. Hexavalent chromium's similarity to sulfate and chromate allow it to be transported into cells via sulfate transport mechanisms. Inside the cell, hexavalent chromium is reduced first to pentavalent chromium, then to trivalent chromium by many substances including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted with the urine. (A12, L16)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

三价铬的暴露和毒性：有一起致命案例报道，一名35岁的女性在摄入50毫升三价铬后出现了严重的酸中毒、大量胃肠道出血、急性肾衰竭和肝脏损伤，并在摄入后12小时死亡。尸检肝脏活检显示脂肪变性，铬浓度为3.6微摩尔/克。肾脏铬浓度为2.6微摩尔/克，出现广泛坏死和缺血性病变。在中国一家铁合金厂的铁铬工人中调查了肾功能的改变（暴露于如钠铬酸盐和铬氢氧化物等铬化合物）。这项研究的结果表明，长期暴露于铬会导致慢性肾损伤，主要涉及近端小管。可以将尿铬浓度大于15微克/克肌酐提出作为肾毒性的阈值剂量，而γ-谷氨酰转移酶、NAG和碱性磷酸酶都是肾损伤的早期敏感指标。动物研究：无数据可用。

IDENTIFICATION AND USE: Chromium trihydroxide (chromic acid) is a green, gelatinous precipitate. It is used as pigment, e.g. Guignet's green; in tanning industry; as a mordant, and as catalyst for organic reactions. HUMAN EXPOSURE AND TOXICITY: Fatal case was described involving 35-year-old woman who developed severe acidosis, massive gastrointestinal hemorrhage, acute renal failure, and hepatic injury following ingestion of chromic acid (50 mL) and died 12 hours after ingestion. Postmortem liver biopsy revealed a fatty degeneration with chromium concentration 3.6 umol/g. The kidney, with chromium concentration 2.6 umol/g, had extensive necrosis and ischemic lesions. Changes in renal function among ferrochromium workers in a ferroalloy facility in China were investigated (exposed to chromium compounds such a sodium-chromate and chromium-hydroxide). The results of this study suggest that long-term exposure to chromium produces chronic renal injury, mainly involving the proximal tubule. A urinary chromium concentration of greater than 15 ug/g of creatinine can be proposed as a threshold dosage for nephrotoxicity, and gamma-glutamyl-transferase, NAG and alkaline-phosphatase are all early sensitive indicators of renal injury. ANIMAL STUDIES: There is no data available.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

三价铬还可以与肽、蛋白质和DNA形成配合物，导致DNA-蛋白质交联、DNA链断裂、DNA-DNA链间交联、铬-DNA加合物、染色体畸变和细胞信号通路的变化。研究表明，它通过过度刺激细胞调节通路和通过激活某些丝裂原活化蛋白激酶来增加过氧化物的水平，从而诱导癌变。它还可能通过将组蛋白去乙酰化酶1-DNA甲基转移酶1复合物与CYP1A1启动子染色质交联，抑制组蛋白修饰，从而引起转录抑制。铬可能通过修饰金属调节转录因子1，导致锌诱导的金属硫蛋白转录的抑制，从而增加其自身的毒性。

Trivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. It has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. It can also cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. (A12, L16, A34, A35, A36)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

证据权重特征：根据美国环保局（EPA）风险评估指南（1986年）中概述的评估对人类致癌性的整体证据权重的标准，三价铬最适当地被指定为D组——关于其人类致癌性尚未分类。使用《致癌物风险评估指南》（1996年建议稿），没有足够的数据来确定三价铬的潜在致癌性……然而，六价铬作为已知人类致癌物的分类，引起了人们对三价铬致癌潜力的关注。人类致癌性数据：在铬酸盐制造和铁铬工业中，通过吸入三价铬和其他铬化合物进行职业暴露已经得到研究；然而，所有暴露都包括对Cr(III)和Cr(VI)的混合暴露。Cr(VI)物种可能是铬工人超额癌症风险报告中病因学上的原因。没有关于单独暴露于Cr(III)的数据，而且数据不足以评估人类致癌潜力。……动物致癌性数据：动物通过口服和吸入暴露于三价铬的数据不支持三价铬致癌性的证据。国际癌症研究机构（IARC）认为，动物数据不足以评估Cr(III)化合物的致癌性。此外，尽管有充分的证据表明与铬暴露相关的呼吸道致癌性，但不能阐明Cr(III)、Cr(VI)、金属铬或可溶性铬与不溶性铬对致癌性的相对贡献……/三价铬（III），不溶性盐类/

WEIGHT OF EVIDENCE CHARACTERIZATION: Applying the criteria for evaluating the overall weight of evidence for carcinogenicity to humans outlined in EPA's guidelines for risk assessment (1986), trivalent chromium is most appropriately designated a Group D -- Not classified as to its human carcinogenicity. Using the Proposed Guidelines for Carcinogen Risk Assessment (1996), there are inadequate data to determine the potential carcinogenicity of trivalent chromium ... However, the classification of hexavalent chromium as a known human carcinogen raises a concern for the carcinogenic potential of trivalent chromium. HUMAN CARCINOGENICITY DATA: Occupational exposure to trivalent chromium and other chromium compounds by inhalation has been studied in the chromate manufacturing and ferrochromium industries; however, exposures all include mixed exposures to both Cr(III) and Cr(VI). Cr(VI) species is the likely etiological agent in reports of excess cancer risk in chromium workers. Data addressing exposures to Cr(III) alone are not available and data are inadequate for an evaluation of human carcinogenic potential. ... ANIMAL CARCINOGENICITY DATA: The data from oral and inhalation exposures of animals to trivalent chromium do not support documentation of the carcinogenicity of trivalent chromium. IARC concluded that animal data are inadequate for the evaluation of the carcinogenicity of Cr(III) compounds. Furthermore, although there is sufficient evidence of respiratory carcinogenicity associated with exposure to chromium, the relative contribution of Cr(III), Cr(VI), metallic chromium, or soluble versus insoluble chromium to carcinogenicity cannot be elucidated... /Chromium (III), insoluble salts/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A4；不可归类为人类致癌物。/铬和Cr(III)无机化合物/

A4; Not classifiable as a human carcinogen. /Chromium and Cr(III) inorganic compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于金属铬和铬(III)化合物的致癌性，在人类中的证据不足。在实验动物中，对于金属铬、铬酸钡和铬(III)化合物的致癌性证据也不足。总体评估：金属铬和铬(III)化合物在人类致癌性方面无法归类（第3组）。/金属铬和铬(III)化合物/

Evaluation: There is inadequate evidence in humans for the carcinogenicity of metallic chromium and of chromium(III) compounds. There is inadequate evidence in experimental animals for the carcinogenicity of metallic chromium, barium chromate and chromium(III) compounds. Overall evaluation: Metallic chromium and chromium(III) compounds are not classifiable as to their carcinogenicity to humans (Group 3). /Metallic chromium and chromium(III) compounds/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

各种(51)铬化合物的排泄和全身保留在大鼠和小鼠中存在很大差异。因此，在小鼠静脉注射剂量7天后，保留的(51)铬分别是Cr-EDTA的2%，Cr-allaxantin的20%，铬氯化物的40%，几乎是铬三氢氧化物的100%。铬三氢氧化物在肝脏中有很高的摄取。

The excretion & whole-body retention of various (51)Cr chromium compounds differed greatly in the rat & mouse. Thus, 7 days after the iv dose to mice, retained (51)Cr was 2% of Cr-EDTA, 20% of Cr-alloxantin, 40% of chromium chloride, & nearly 100% of chromium trihydroxide. There was high uptake of chromium trihydroxide in the liver.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  chromium(VI) oxide 在 二硫化碳 作用下， 以 二硫化碳 为溶剂， 生成 羰基硫
  参考文献：
  名称：

  Armstrong, H. E., Chemische Berichte, 1869, vol. 2, p. 112 - 113

  摘要：

  DOI：
• 作为产物：
  描述：

  铬 在 氧气 作用下， 生成 chromium(VI) oxide
  参考文献：
  名称：

  Rossini, F. D.; Wagman, D. D.; Evans, W. H., Circ. Br. Stand. Nr. 500 (1952) 285

  摘要：

  DOI：
• 作为试剂：
  描述：

  N-(tert-butyl)-2-hydroxy-2-phenylethane-1-sulfonamide 在 哌啶 、 chromium(VI) oxide 、 硫酸 、 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 反应 14.0h， 生成 (E)-1-(3-fluorophenyl)-3-oxo-3-phenylprop-1-ene-2-sulfonamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Chalconesulfonamides: En Route to Proapoptotic Agents with Antiestrogenic Potency

  摘要：

  Breast and other estrogen receptor α-positive cancers tend to develop resistance to existing drugs. Chalcone derivatives possess anticancer activity based on their ability to form covalent bonds with targets acting as Michael acceptors. This study aimed to evaluate the anticancer properties of a series of chalcones (7a–l) with a sulfonamide group attached to the vinyl ketone moiety. Chalconesulfonamides showed a potent antiproliferative effect at low micromolar concentrations against several cancer cell lines, including ERα-positive 4-hydroxytamoxifen-resistant MCF7/HT2. Immunoblotting of samples treated with the lead compound 7e revealed its potent antiestrogenic activity (ERα/GREB1 axis) and induction of PARP cleavage (an apoptosis marker) in breast cancer cells. The obtained compounds represent a promising basis for further development of targeted drugs blocking hormone pathways in cancer cells.

  DOI：

  10.3390/ph17010032

文献信息

• Kinetics and mechanism of quinolinium dichromate mediated oxidation of sugar alcohols in Bronsted acid media
  作者：Satish Babu Kodali、Narendar Reddy Jakku、Chinna Rajanna Kamatala、Rajeshwar Rao Yerraguntla

  DOI：10.1002/kin.21339

  日期：2020.3

  Bronsted acid catalyzed oxidation of certain sugar alcohols (polyols) has been studied by quinolinium dichromate (QDC) using aqueous sulfuric, perchloric, and hydrochloric acids at different temperatures. At constant acidity, reaction kinetics revealed the second‐order kinetics with a first order in [Alcohol] and [QDC]. Zucker‐Hammett, Bunnett, and Bunnett‐Olsen criteria were used to analyze acid‐dependent

  重铬酸喹啉鎓（QDC）使用硫酸，高氯酸和盐酸水溶液在不同温度下研究了布朗斯台德酸催化某些糖醇（多元醇）的氧化。在恒定的酸度下，反应动力学在[酒精]和[QDC]中显示了一级动力学。Zucker-Hammett，Bunnett和Bunnett-Olsen标准用于分析酸依赖的速率加速。（日志Bunnett-Olsen的曲线ķ + ħ ν）与（ħ ν +日志[H + ]），和（日志ķ）与（ħ ν +日志[H + ]），得到的斜率值（φ和φ *分别> 0.47），表明在硫酸，高氯酸和盐酸水溶液存在下，水分子在QDC氧化醇氧化机理的缓慢步骤中起着质子传递剂的作用。
• Coupled-substituted double-layer Aurivillius niobates: structures, magnetism and solar photocatalysis
  作者：Sonia Rani、Gollapally Naresh、Tapas Kumar Mandal

  DOI：10.1039/c9dt04339j

  日期：——

  ranging from 2.25-2.94 eV. While the compounds show paramagnetic behaviour with no indication of magnetic phase transition or ordering in the temperature range 5-300 K, the Mn compound stabilizes with a low-spin (LS) configuration in contrast to all others (Cr, Fe and Co compounds), which adopt a high-spin (HS) configuration. The stabilization of the LS configuration (t42g) of the Mn compound occurs

  层状钙钛矿用于阳光驱动催化的研究在当代无机材料研究中引起了很多关注。尽管三维钙钛矿的组成改性是普遍存在的，但在钙钛矿层厚度低时，在层状钙钛矿尤其是铌酸盐的情况下，它们很少出现。我们在这里报告通过采用SrBi2Nb2O9的异价偶联取代策略，对一系列无铅双层铌酸奥利奇柳酸盐LaBi2Nb1.5M0.5O9（M = Cr，Mn，Fe，Co）进行固态合成。使用P-XRD数据对化合物的Rietveld结构进行的改进表明，在非中心对称的A21am空间群中，与母体同构的3dn过渡金属结合的双层Aurivillius niobates的形成。这些化合物在可见光区域显示出光吸收，吸收尾部延伸至约650 nm，带隙范围为2.25-2.94 eV。尽管这些化合物在5-300 K的温度范围内表现出顺磁行为，但没有磁性相变或有序的迹象，但与所有其他化合物（Cr，Fe和Co化合物）相比，Mn化合物以低旋转（LS）构型稳定。
• Solid solutions of flexible host–guest supramolecules for tuning molecular motion and phase transitions
  作者：Xun-Hui Zhou、Ying Zeng、Shao-Bin Tang、Zi-Ru Yu、Li-Ming Cao、Zi-Yi Du、Chun-Ting He

  DOI：10.1039/d1cc02061g

  日期：——

  solid-solution strategy and demonstrate an example of how two related yet non-isostructural crystalline host–guest compounds can form molecular solid solutions. Interestingly, such a strategy can effectively and continuously modulate the molecular motion and phase transition in them, as revealed by the variable-temperature/frequency dielectric responses.

  通过利用超分子复合物而不是单个分子作为可变形和弹性置换成分，我们提出了一种固溶策略，并展示了两个相关但非同构的晶体主客体化合物如何形成分子固溶体的例子。有趣的是，正如可变温度/频率介电响应所揭示的那样，这种策略可以有效且连续地调节其中的分子运动和相变。
• Discovery and synthesis of 3- and 21-substituted fusidic acid derivatives as reversal agents of P-glycoprotein-mediated multidrug resistance
  作者：Mengqi Guo、Qianwen Ren、Binghua Wang、Wentao Ji、Jingxuan Ni、Yaqi Feng、Yi Bi、Jingwei Tian、Hongbo Wang

  DOI：10.1016/j.ejmech.2019.111668

  日期：2019.11

  In this study, we synthesized 23 fusidic acid (FA) derivatives and screened them for tumor drug resistance reversal activity and cytotoxicity toward the KBV (multidrug-resistant oral epidermoid carcinoma) cell line based on MTT assay. Tumor resistance reversal activity of fusidic acid (FA) derivatives was discovered for the first time. Our results showed that compound 1 enhanced the cytotoxicity of

  在这项研究中，我们合成了23种夫西地酸（FA）衍生物，并根据MTT分析筛选了它们对KBV（多药耐药口腔表皮样癌）细胞系的肿瘤耐药逆转活性和细胞毒性。首次发现了夫西地酸（FA）衍生物的抗肿瘤逆转活性。我们的结果表明，化合物1以5μM的浓度增强了紫杉醇对耐药KBV细胞的细胞毒性。化合物1使KBV细胞对紫杉醇敏感，使其停滞在G2 / M期并诱导细胞凋亡。进一步的研究表明，化合物1通过增加P-gp的ATPase活性来抑制P-糖蛋白（P-gp）的药物外排活性，而不影响其表达。还初步研究了FA衍生物的构效关系（SAR）。我们的发现表明，化合物1是用于设计未来具有改善的肿瘤耐药性逆转活性的FA衍生物的有前途的先导化合物。
• Structural Activity of Unsaturated Alcohols and Oxidation Towards Pyrazinium Chlorochromate
  作者：K. Anbarasu、K. K. Ilavenil

  DOI：10.13005/ojc/350156

  日期：2019.2.28

  The kinetics of oxidation of allyl, crotonyl, styryl carbinol by pyrazinium chlorochromate (PzCC) has been investigated in 60% acetic acid medium.The order was found to be first order with respect to [oxidant], [substrate] and [H+.]. The rate of the oxidant decreased with increase in [PzCC] and increased with increase in the percentage of acetic acid. The addition of sodium perchlorate did not show

  在60％乙酸介质中研究了吡嗪鎓氯铬酸盐（PzCC）对烯丙基，巴豆酰基，苯乙烯基甲醇的氧化动力学。发现该序列相对于[氧化剂]，[底物]和[H +]为一阶。 。氧化剂的比例随着[PzCC]的增加而降低，并且随着乙酸的百分比的增加而升高。高氯酸钠的添加没有显示速率常数的任何变化。基于动力学结果，提出了不饱和醇与六价铬氧化剂的机理。观察到不饱和醇的反应性是烯丙醇＜巴豆醇＜苯乙烯基甲醇。