arsenic trioxide

• 分子结构分类: 无机化合物 - 混合金属/非金属化合物 - 类金属有机物
• 英文名称: arsenic trioxide
• 英文别名: ATO；Arsenic(III) oxide；[74As]-Arsenic(III) oxide
• 化学式: As₂O₃
• 分子量: 197.841
• InChiKey: IKWTVSLWAPBBKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.07
• 重原子数：
  5
• 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：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

无机、冻干的三氧化二砷在溶液中立即被水解为砒酸——这似乎是三氧化二砷的药理活性物种。进一步的代谢涉及砒酸的氧化生成砒酸，以及砒酸通过肝脏中的甲基转移酶进行氧化甲基化，生成一甲基砷酸（MMA）和二甲基砷酸（DMA）。MMA和DMA都有相对较长的半衰期，并且在多次给药后可以累积，其累积程度取决于所讨论的给药方案。

Inorganic, lyophilized arsenic trioxide, when placed in solution, is immediately hydrolyzed to arsenous acid - this appears to be the pharmacologically active species of arsenic trioxide. Further metabolism involves the oxidation of arsenous acid to arsenic acid, and an oxidative methylation of arsenous acid to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) by methyltransferases in the liver. Both MMA and DMA have relatively long half-lives and can accumulate following multiple doses, the extent of which depends upon the dosing regimen in question.

来源:DrugBank

代谢

化学形态学研究已经表明，二甲基砷酸和甲烷砷酸是人类通过吸入三氧化二砷后尿液中主要存在的砷形态。

CHEMICAL SPECIATION STUDIES HAVE SHOWN THAT DIMETHYLARSINIC ACID & METHANEARSONIC ACID ARE PRIMARY FORMS OF ARSENIC PRESENT IN URINE OF HUMANS EXPOSED TO ... ARSENIC TRIOXIDE BY INHALATION.

来源:Hazardous Substances Data Bank (HSDB)

代谢

砷冶炼工人的尿液分析显示，二甲砷酸是主要的种类，其次是甲基砷、三价砷和五价砷。

Urinary profiles of arsenic smelter workers showed that dimethylarsenic acid was the major species followed by methyl arsenic, trivalent arsenic, and pentavalent arsenic.

来源:Hazardous Substances Data Bank (HSDB)

代谢

四个砷物种的尿浓度，五价（As(V)）和三价（As(III)）无机砷，单甲基砷酸（MMAA）和二甲基砒酸（DMAA），在急性中毒后几天内分别跟踪了两个自杀未遂者摄入砒霜和正砷酸钠的情况。总砷浓度范围从1.6到18.7毫克/升。3或4天后，毒性较低的甲基化物种，特别是二甲基砒酸的逐渐增加，支持了甲基化作为一种天然解毒机制的构想，这是人体对无机砷进行生物转化的整体还原/甲基化序列的一部分。然而，在极端情况下，摄入后立即氧化As(III)为As(V)的额外可能性被最初高尿As(V)，As(III)，单甲基砷酸和二甲基砒酸的存在所暗示，这可能在两种情况下反映了物种依赖的消除速率和与组织的反应性差异，以及甲基化的效率。

Urinary concentrations of the four arsenic species, pentavalent (As(V)) and trivalent (As(III)) inorganic arsenic, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA), were followed for several days subsequent to the acute intoxication of two human subjects by arsenic trioxide and sodium orthoarsenate, respectively, in unsuccessful suicide attempts. Total arsenic concentrations ranged from 1.6 to 18.7 mg/1. The increasing predominance of the less toxic methylated species, especially dimethylarsinic acid, after 3 or 4 days supports the concept of methylation as a natural detoxification mechanism as part of an overall reduction/methylation sequence involved in the biotransformation of inorganic arsenic by the human body. However, the additional possibility of oxidation of As(III) to As(V) in vivo under extreme immediate postingestion conditions is suggested by initial high urinary As(V), As(III), monomethylarsonic acid and dimethylarsinic acid in both cases probably reflect species dependent differences in rates of direct elimination and reactivity with tissues as well as the efficiency of methylation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

大鼠肝细胞质通过甲基化使无机砷失活；S-腺苷甲硫氨酸是甲基供体，还原型谷胱甘肽对充分发挥活性是必需的。途径涉及形成一种单甲基化代谢物，这种代谢物要么迅速进一步甲基化成二甲基衍生物，要么自发氧化成单甲基砷酸。二甲基化代谢物产生二甲基砷酸。第一次甲基化反应是限速步骤，可以被谷胱甘肽刺激，并且由不同于转移第二个甲基团的酶催化。后者对无机砷的抑制作用敏感。大量的巯基可能会通过减少自由三价砷的量来阻止甲基化反应。

Rat liver cytosol inactivates inorganic arsenic through methylation; S-adenosylmethionine is the methyl group donor and reduced glutathione is required for full activity. ... Pathway involves the formation of a monomethylated metabolite which is either rapidly further methylated into a dimethylated derivative or is spontaneously oxidized into monomethylarsinic acid. The dimethylated metabolite gives rise to dimethylarsinic acid. The first methylation reaction is rate limiting, can be stimulated by glutathione and is catalyzed by an enzyme different from that which transfers the second methyl group. The latter is sensitive to inhibition by inorganic arsenic. ... A large excess of thiol groups may prevent the methylation reactions probably by decreasing the amount of free trivalent arsenic.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

致癌性分类：1）人类证据：充分；2）动物证据：有限。对人类致癌风险的总体评估为第1组：对人类致癌。注意：此评估适用于整个化学物质组，而不一定适用于组内所有单个化学物质。/砷和砷化合物/

Classification of carcinogenicity: 1) evidence in humans: sufficient; 2) evidence in animals: limited. Overall summary evaluation of carcinogenic risk to humans is Group 1: Carcinogenic to humans. NOTE: This evaluation applies to the group of chemicals as a whole and not necessarily to all individual chemicals within the group. /Arsenic and arsenic compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A1：确认的人类致癌物。/砷和无机砷化合物/

A1: Confirmed human carcinogen. /Arsenic and inorganic compounds, as As/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：有足够的人类证据表明饮用水中的砷可导致膀胱癌、肺癌和皮肤癌... 总体评估：饮用水中的砷对人类具有致癌性（第1组）。/饮用水中的砷/

Evaluation: There is sufficient evidence in humans that arsenic in drinking-water causes cancers of the urinary bladder, lung and skin ... Overall evaluation: Arsenic in drinking-water is carcinogenic to humans (Group 1). /Arsenic in drinking water/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

... 在实验动物中，对于亚砷酸钠、砷酸钙和三氧化二砷的致癌性有有限的证据 ... /饮用水中的砷/

... There is limited evidence in experimental animals for the carcinogenicity of sodium arsenite, calcium arsenate and arsenic trioxide ... /Arsenic in drinking water/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：大多数来源认为，在母亲抗肿瘤药物治疗期间，母乳喂养是禁忌的。在间歇性治疗期间，可能可以在适当的母乳禁食期后安全地进行母乳喂养；制造商建议在最后一剂后的禁食期为1周。化疗可能会不利地影响母乳的正常微生物组和化学成分。在怀孕期间接受化疗的妇女更有可能在哺乳婴儿时遇到困难。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：对74名在怀孕第二或第三季度在一个中心接受癌症化疗的妇女进行电话随访研究，以确定她们产后是否成功进行母乳喂养。只有34%的妇女能够完全母乳喂养她们的婴儿，而66%的妇女报告经历了母乳喂养困难。这与其他22位在怀孕期间被诊断但未接受化疗的母亲91%的母乳喂养成功率形成了对比。其他具有统计学意义的相关性包括：1. 有母乳喂养困难的母亲平均接受了5.5个周期的化疗，而没有困难的母亲平均接受了3.8个周期；2. 有母乳喂养困难的母亲在怀孕期间平均提前3.4周接受了第一个周期的化疗。在接受含有氟尿嘧啶方案的9名妇女中，有8名有母乳喂养困难。

◉ Summary of Use during Lactation:Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence; the manufacturer recommends an abstinence period of 1 week after the last dose. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 9 women who received a fluorouracil-containing regimen, 8 had breastfeeding difficulties.

来源:Drugs and Lactation Database (LactMed)

吸收、分配和排泄

• 消除途径

三价砷在人体内主要是甲基化的，并通过尿液排出。

Trivalent arsenic is mostly methylated in humans and excreted in urine.

来源:DrugBank

吸收、分配和排泄

人和动物的数据都表明，超过80%摄入的溶解无机三价砷从胃肠道被吸收。...在砷三氧化物的情况下，它只微溶于水，胃肠道的吸收将取决于诸如粒子大小和胃液pH等因素。

BOTH HUMAN & ANIMAL DATA INDICATE THAT OVER 80% OF INGESTED DOSE OF DISSOLVED INORG TRIVALENT ARSENIC IS ABSORBED FROM GI TRACT. ... IN CASE OF ARSENIC TRIOXIDE, WHICH IS ONLY SLIGHTLY SOL IN WATER, GI ABSORPTION WILL BE DEPENDENT ON FACTORS SUCH AS PARTICLE SIZE & PH OF THE GASTRIC JUICES.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠中进行为期最多52天的215 ppm砒霜（砒霜三氧化物）饮食管理后，发现最高砒霜含量在肾脏和肝脏中，而在毛发、大脑、骨骼、肌肉和皮肤中的含量相对较低。三价砒霜在人體内转化为五价砒霜，后者会被肾脏迅速排出。

FOLLOWING DIETARY ADMIN OF 215 PPM ARSENIC IN FORM OF ... ARSENIC TRIOXIDE FOR UP TO 52 DAYS IN RATS, HIGHEST ... LEVELS ... WERE FOUND IN KIDNEYS & LIVER & RELATIVELY LOWER LEVELS IN HAIR, BRAIN, BONE, MUSCLE & SKIN. ... TRIVALENT ARSENIC ... IS CONVERTED TO ... /PENTAVALENT ARSENIC IN MAN/ WHICH IS RAPIDLY EXCRETED BY KIDNEYS.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

以三氧化砷形式给予猴子口服1毫克/千克体重的砷，大约有80%从肠道吸收；在14天内，约75%的给药剂量被排出，主要是通过尿液。

ORAL ADMIN OF 1 MG/KG BODY WT ARSENIC AS ARSENIC TRIOXIDE TO MONKEYS RESULTED IN APPROXIMATELY 80% ABSORPTION FROM THE GUT; 75% OF THE ADMIN DOSE WAS EXCRETED WITHIN 14 DAYS, PRIMARILY IN URINE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

21天大的雄性和雌性大鼠被给予含有26.8或215毫克/千克饮食砒霜的饮食，随意进食。随后三胎的幼崽被评估，以及第二代的第一胎幼崽。在第一代的第一个幼崽中发现的新生儿含量低于后来的幼崽...

... MALE & ... FEMALE RATS, 21 DAYS OF AGE WERE GIVEN DIET CONTAINING 26.8 OR 215 MG/KG OF DIET ARSENIC AS ARSENIC TRIOXIDE AD LIBITUM. ... LITTERS OF FOLLOWING 3 PREGNANCIES WERE EVALUATED, AS WELL AS FIRST LITTER OF SECOND GENERATION. AMT ... FOUND IN NEWBORNS WAS LOWER IN FIRST LITTER OF FIRST GENERATION ... THAN LATER LITTERS ...

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  arsenic trioxide 生成
  参考文献：
  名称：

  CLEMENT, THOMAS P. (II);LI, TAIE;HAGER, JOHN P.

  摘要：

  DOI：
• 作为产物：
  描述：

  三氯化砷 生成 arsenic trioxide
  参考文献：
  名称：

  ZHIGARNOVSKIJ, B. M.;PANASYUK, G. L.;LAZAREV, V. B.;FALKENGOF, A. T.;SIXA+

  摘要：

  DOI：
• 作为试剂：
  描述：

  氯乙酸 在 arsenic trioxide 、 水 、 sodium hydroxide 作用下， 以81 %的产率得到胂羧基乙酸
  参考文献：
  名称：

  一种共价靶向砷抑制剂及其制备方法和应用

  摘要：

  本发明公开了一种共价靶向砷抑制剂及其制备方法和应用，其结构式为 本发明设计的共价靶向砷抑制剂具有靶向基团和三价砷(AsIII)反应基团，靶向基团为(R)‑3‑(4‑苯氧基苯基)‑1‑(哌啶‑3‑基)‑1H‑吡唑并[3，4‑d]嘧啶‑4‑胺基团(Targeting group)，能够高度特异性地靶向布鲁顿酪氨酸激酶(BTK)，三价砷(AsIII)反应基团可以高亲和力的共价结合BTK半胱氨酸残基(Cys481)，有效抑制BTK介导的B细胞受体(BCR)信号通路，导致Ramos细胞死亡，并具有较好的在体抗肿瘤增殖活性。

  公开号：

  CN115322226A

文献信息

• Palladium Chemistry in Anhydrous HF/AsF ₅ Superacid Medium
  作者：Zoran Mazej、Primož Benkič、Alain Tressaud、Boris Žemva

  DOI：10.1002/ejic.200300681

  日期：2004.5

  Pd metal dissolves in anhydrous HF (aHF) acidified with AsF5 in the presence of F2 at ~ 298 K to give a blue-green solution from which green Pd(AsF6)2 can be isolated...

  在 F2 存在下，Pd 金属溶解在用 AsF5 酸化的无水 HF (aHF) 中，温度约为 298 K，得到蓝绿色溶液，从中可以分离出绿色 Pd(AsF6)2...
• A re-investigation of arsenoacetic acid, (AsCH2COOH)n
  作者：Brian K. Nicholson、Peter S. Wilson、Adelle Nancekivell

  DOI：10.1016/j.jorganchem.2013.07.056

  日期：2013.11

  obtained for arsonoacetic acid, As(CH2COOH)O3H2, and its barium and sodium salts. The X-ray crystal structure of the free acid is isomorphous with phosphonoacetic acid. Reduction gave the As(I) compound arsenoacetic acid, (AsCH2COOH)n which was shown by ESI-MS to contain cyclic species based on As–As bonds, with n mainly 3–6. The X-ray crystal structure of the hexamer was determined as the pyridine solvate

  已获得有关砷乙酸，As（CH 2 COOH）O 3 H 2及其钡和钠盐的详细光谱数据。游离酸的X射线晶体结构与膦酰基乙酸同构。还原得到的As（I）化合物砷乙酸（AsCH 2 COOH）n由ESI-MS显示包含基于As-As键的环状物质，n主要为3-6。六聚体的X射线晶体结构确定为吡啶溶剂化物，并显示在褶皱的椅子构象中具有六环As 6环，在赤道位置带有–CH 2 COOH基团，每个H键键合到吡啶分子中的吡啶分子上。格子。
• Synthesis and Characterization of the New Series of Chromium−Group 15 Hydride Complexes [Et₄N]₂[HE{Cr(CO)₅}₃] (E = As, Sb)
  作者：Jiann-Jang Cherng、Gene-Hsiang Lee、Shie-Ming Peng、Chuen-Her Ueng、Minghuey Shieh

  DOI：10.1021/om990717z

  日期：2000.2.1

  The new series of trigonal-pyramidal chromium complexes [HECr(CO)5}3]2- (E = As (Ia), Sb (Ib)) were obtained from the reactions of E2O3 (E = As, Sb) with Cr(CO)6 in concentrated KOH methanolic solution. These are the first examples of group 6 complexes containing E−H fragments (E = As, Sb), and the hydrogens are shown to be more hydridic than those in the related iron complexes due to the more electropositive

  新系列三角锥型铬配合物[HE 的Cr（CO）5 } 3 ] 2 -（E =如（IA），锑（磅））购自E的反应得到的2 ö 3（E =如， Sb）和Cr（CO）6在浓KOH甲醇溶液中的混合溶液。这些是含有EH片段（E = As，Sb）的第6族配合物的第一个例子，并且由于Cr具有更强的正电性，因此氢比相关铁配合物中的氢更具有亲水性。
• La[AsO3]: Lanthanum Oxoarsenate(III) with K[ClO3]-Type Crystal Structure
  作者：Sebastian J. Metzger、Gunter Heymann、Hubert Huppertz、Thomas Schleid

  DOI：10.1002/zaac.201100552

  日期：2012.6

  Colorless, transparent single crystals of the lanthanum oxoarsenate(III) La[AsO3] emerged after exposing an equimolar mixture of La2O3 and As2O3 to high pressure (11.5 GPa) and high temperature (1000 °C). The air- and water-stable compound crystallizes isotypically with K[ClO3] and thus can be described in the monoclinic space group P21/m with the lattice constants a = 442.91(4), b = 531.40(5), c =

  将等摩尔的 La2O3 和 As2O3 混合物暴露于高压 (11.5 GPa) 和高温 (1000 °C) 后，会出现无色透明的氧代砷酸镧 (III) La[AsO3] 单晶。空气和水稳定的化合物与 K[ClO3] 同型结晶，因此可以描述在单斜空间群 P21/m 中，晶格常数 a = 442.91(4), b = 531.40(5), c = 622.83( 6) pm 和 β = 105.564(3)°，Z = 2。就像 K[ClO3] 中的 K+ 阳离子一样，La[AsO3] 中晶体学上独特的 La3+ 阳离子被九个氧原子 (d(La3+–O2– ) = 254–287 pm)。相应的[LaO9]15-多面体首先通过两条边相互连接，形成沿a轴延伸的无限[LaO7]11-}链。这些链通过顶点共享生成 [LaO6]9-} 层，平行于 ab 平面展开，它们通过公共边沿 [001] 进一步
• Ein Metaarsenat(V) Anion neuartiger Konstitution in AgAsO3
  作者：J. Curda、E.-M. Peters、M. Jansen

  DOI：10.1002/zaac.200300388

  日期：2004.3

  nebeneinander in oktaedrischer und tetraedrischer Koordination enthalt. Es weist damit Struktureinheiten wie As2O5 auf, die daruber hinaus in ahnlicher Weise verknupft sind. Metaarsenate(V) Anion of Novel Constitution in AgAsO3 AgAsO3 was prepared, for the first time, through solid state reaction of Ag2O and As2O3, or As, respectively, while applying an elevated oxygen pressure (T = 500 °C, p(O2) = 2 kbar, 1—2

  AgAsO3 wurde durch Festkorperreaktion zwischen Ag2O 和 As2O3 oder As unter erhohtem Sauerstoffdruck erstmals dargestellt (T = 500 °C, p(O2) = 2 kbar, 1-2 Tage)。Nach den Ergebnissen der Einkristallrontgenstrukturanalysis (Pca21; a = 1948.8(3), b = 660.0(1), c = 1266.1(3) pm; Z = 24; 4741 unabh. Reflexe; R1 = 0.06 O/244 )(AsO2/1O2/2)2] ein neuartiges Polyanion vor, das Arsen nebeneinander in oktaedrischer