1,4-二巯基-2,3-丁二醇 | 7634-42-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1,4-二巯基-2,3-丁二醇
• 英文名称: diothiothreitol
• 英文别名: DTT；dithiothreitol；DL-dithiothreitol；1,4-dithiothreitol；dithiotreitol；1,4-dimercaptobutane-2,3-diol；(±)-dithiothreitol；1,4-dithio-DL-threitol；DL-1,4-dithiothreitol；DDT；DL-threo-1,4-dimercapto-2,3-butanediol；Dithioerythritol；1,4-bis(sulfanyl)butane-2,3-diol
• CAS: 7634-42-6
• 化学式: C₄H₁₀O₂S₂
• mdl: MFCD00065459
• 分子量: 154.254
• InChiKey: VHJLVAABSRFDPM-UHFFFAOYSA-N

物化性质

• 颜色/状态：
  Needles from ether
• 气味：
  Characteristic
• 熔点：
  62.75 °C
• 溶解度：
  In water, 4.94X10+5 mg/L at 25 °C (est)
• 蒸汽压力：
  1.28X10-4 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Chemical stability: May decompose on exposure to moist air or water. Stable under recommended storage conditions.
• 分解：
  Hazardous decomposition products formed under fire conditions: Carbon oxides, sulfur oxides.

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  42.5
• 氢给体数：
  4
• 氢受体数：
  4

ADMET

代谢

两名晚期（尿毒症）婴儿型肾囊性胱氨酸病（INC）的男性患者通过口服还原剂二硫苏糖醇（DTT）进行治疗，剂量不超过每天三次，每次25毫克/千克体重。在两名患者中获得了三个连续观察期：服用巯基（8.5个月）；停用巯基（8-9个月）；再次服用巯基（7个月或更长时间）……虽然化学方法不能可靠地检测和测量生物流体中的DTT，但初步证据表明，口服DTT的患者的尿液中可以检测到氧化DTT的硅基衍生物。这一发现表明巯基被吸收并排出体外。

Two male patients with late stage (uremic) infantile nephropathic cystinosis (INC) were treated by mouth with the reducing agent dithiothreitol (DTT), at doses not exceeding 25 mg/kg body weight three times per day. Three sequential periods of observation were obtained in both patients: on thiol (8.5 months); off thiol (8-9 months); on thiol again (7 months or longer)... Whereas chemical methods are not reliable for detecting and measuring DTT in biologic fluids, preliminary evidence indicates that a silylated derivative of oxidized DTT can be detected in the urine of patients receiving DTT by mouth. This finding suggests that the thiol is absorbed and excreted.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：1,4-二硫苏糖醇（DTT）常用于涉及蛋白质或肽的生化实验中，保护巯基不被氧化，并减少半胱氨酸之间的二硫键。它还用于研究蛋白质二硫键的交换反应，DTT能够保持谷胱甘肽的还原状态。它已被测试作为胱氨酸病或由离子或金属毒性引起的医疗条件的实验性治疗。人体研究：DTT能触发HL-60细胞的凋亡。DTT用于液化哮喘患者收集的痰液。两名晚期（尿毒症）婴儿肾病性胱氨酸病男性患者口服还原剂DTT治疗，剂量不超过每天三次，每次25 mg/kg体重。除了在最大剂量范围内出现恶心和呕吐外，没有观察到明显的毒性。一名受试者在研究的第24个月因尿毒症死亡。动物研究：DTT对大鼠心脏和肠道组织的抑制严重限制了其作为抗氧化剂的使用，以保护在药理测试中容易空气氧化的药物。二硫苏糖醇治疗可以模仿艰难梭菌强效细胞毒素毒素B的细胞内激活。

IDENTIFICATION AND USE: 1,4-Dithiothreitol (DTT) is frequently used in biochemical experiments that involve proteins or peptides, protecting sulfhydryl groups from oxidation and reducing disulfide bonds between cysteines. It is also used in the study of disulfide exchange reactions of protein disulfides, and DTT is able to keep glutathione in the reduced state. It has been tested as experimental therapy in cystinosis or medical conditions resulting from ion or metal toxicity. HUMAN STUDIES: DTT triggers apoptosis in HL-60 cells. DTT is used in the liquefication of sputum recovered from asthma patients. Two male patients with late stage (uremic) infantile nephropathic cystinosis were treated by mouth with the reducing agent DTT, at doses not exceeding 25 mg/kg body weight three times per day. Other than nausea and vomiting at the maximum dose range, no apparent toxicity was observed. One subject died in uremia in the 24th month of the study. ANIMAL STUDIES: Depression of rat's heart and intestinal tissues by DTT severely limits its use as antioxidant to protect readily air oxidizable drugs during pharmacological testing with these standard tissue preparations. Treatment with dithiothreitol can mimic intracellular activation of the potent cytotoxin of Clostridium difficile, toxin B.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

广泛使用的巯基抗氧化剂（二硫苏糖醇、谷胱甘肽和N-乙酰半胱氨酸）与羟基钴胺素（维生素B12）结合，对人类淋巴细胞白血病细胞系HL60具有毒性作用。巯基和维生素B12的联合治疗导致早期溶酶体不稳定和细胞凋亡性死亡。这种细胞毒性效果可被胱天蛋白酶抑制剂消除。铁螯合剂去铁胺部分预防了细胞死亡，而溶酶体蛋白酶抑制剂pepstatin没有产生保护作用。

The extensively used thiol antioxidants (dithiothreitol, glutathione, and N-acetylcysteine) in combination with hydroxycobalamine (vitamin B12) gain toxic activity in relation to human lymphocytic leukemia cell line HL60. Combined treatment with thiol and vitamin B12 was followed by early destabilization of lysosomes and apoptotic death of cells. The cytotoxic effect was abolished by caspase inhibitors. An iron-chelating agent deferoxamine partly prevented cell death, while lysosomal protease inhibitor pepstatin produced no protective effect.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

砒霜是一种自然存在的有毒类金属，饮用含有As2 O3的水被认为与神经毒性、肝脏损伤、黑脚病、高血压和癌症的风险增加有关。相反，砒霜一直是传统中医中使用的一种古老的药物，具有显著的抗癌活性，特别是在治疗急性早幼粒细胞白血病和慢性伤口愈合方面。然而，砒霜对实体癌细胞，如口腔癌细胞，的细胞毒性和详细作用机制在很大程度上是未知的。在本研究中，我们主要培养来自口腔癌患者的四对肿瘤和非肿瘤细胞，并用砒霜单独处理或与二硫苏糖醇（DTT）联合处理细胞。结果显示，0.5 uM砒霜加20 uM DTT能显著诱导口腔癌细胞死亡，但对非肿瘤细胞无影响。同时，砒霜加DTT能上调Bax和Bak，下调Bcl-2和p53，导致口腔癌细胞线粒体膜电位的丧失。另一方面，砒霜还触发了内质网应激，并增加了葡萄糖调节蛋白78、钙蛋白酶1和2的水平。我们的结果表明，DTT能够协同增强砒霜对口腔癌细胞的杀伤作用，同时对非肿瘤细胞无毒。这种组合在口腔癌治疗中具有临床应用的潜力，值得进一步研究。

Arsenic is naturally occurring toxic metalloid and drinking As2 O3 containing water are recognized to be related to increased risk of neurotoxicity, liver injury, blackfoot disease, hypertension, and cancer. On the contrary, As2 O3 has been an ancient drug used in traditional Chinese medicine with substantial anticancer activities, especially in the treatment of acute promyelocytic leukemia as well as chronic wound healing. However, the cytotoxicity and detail mechanisms of As2 O3 action in solid cancer cells, such as oral cancer cells, are largely unknown. In this study, we have primarily cultured four pairs of tumor and nontumor cells from the oral cancer patients and treated the cells with As2 O3 alone or combined with dithiothreitol (DTT). The results showed that 0.5 uM As2 O3 plus 20 uM DTT caused a significant cell death of oral cancer cells but not the nontumor cells. Also As2 O3 plus DTT upregulated Bax and Bak, downregulated Bcl-2 and p53, caused a loss of mitochondria membrane potential in oral cancer cells. On the other way, As2 O3 also triggered endoplasmic reticulum stress and increased the levels of glucose-regulated protein 78, calpain 1 and 2. Our results suggest that DTT could synergistically enhance the effects of As2 O3 on killing oral cancer cells while nontoxic to the nontumor cells. The combination is promising for clinical practice in oral cancer therapy and worth further investigations.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

之前发现，维生素B12b通过催化活性氧种类的形成，显著增强了抗坏血酸的细胞毒性，而抗氧化剂二硫苏糖醇（DTT）与过氧化氢酶相比，并不能防止细胞毒性。因此，在本研究中，我们检验了B12b是否能够增强DTT的细胞毒性。结果显示，B12b强烈增加了DTT的细胞毒性。向DTT中添加维生素B12b催化了培养基中过氧化氢的生成和剧烈积累，在7分钟内达到260微摩尔的浓度。由B12b和DTT组合（DTT + B12b）诱导的细胞外氧化爆发伴随着细胞内氧化应激、溶酶体的不稳定和DNA的损伤。DNA损伤的积累导致了凋亡性细胞死亡的启动，包括caspase-3的激活和细胞色素c的释放。抗氧化剂丙酮酸和过氧化氢酶完全预防了DTT + B12b诱导的氧化应激和细胞死亡。铁螯合剂去铁胺和邻菲啰啉预防了该组合的基因和细胞毒性，尽管它们并未减少外源性氧化爆发，这表明细胞内铁在组合的细胞毒性中发挥了关键作用。因此，维生素B12b显著增强了DTT的细胞毒性，催化过氧化氢的生成并诱导细胞内外氧化应激、早期溶酶体不稳定和铁依赖性DNA损伤。

It has been found previously that vitamin B12b amplifies significantly the cytotoxic effects of ascorbic acid by catalyzing the formation of reactive oxygen species, and the antioxidant dithiothreitol (DTT), in contrast to catalase, does not prevent the cytotoxicity. Therefore, in this study we examined whether B12b is able to enhance the cytotoxicity of DTT. It was revealed that B12b strongly increases the cytotoxic effect of DTT. Vitamin B12b added to DTT catalyzed the generation and drastic accumulation of hydrogen peroxide in culture medium to a concentration of 260 microM within 7 min. The extracellular oxidative burst induced by the combination of B12b and DTT (DTT + B12b) was accompanied by intracellular oxidative stress, the destabilization of lysosomes, and damage to DNA. The accumulation of DNA lesions led to the initiation of apoptotic cell death, including the activation of caspase-3 and the release of cytochrome c. The antioxidants pyruvate and catalase completely prevented the DTT + B12b-induced oxidative stress and cell death. The iron chelators desferrioxamine and phenanthroline prevented the geno- and cytotoxic action of the combination although they did not reduce the exogenous oxidative burst, indicating a key role for intracellular iron in the cytotoxicity of the combination. Thus, vitamin B12b dramatically enhances the cytotoxicity of DTT, catalyzing the generation of hydrogen peroxide and inducing extra- and intracellular oxidative stress, early destabilization of lysosomes, and iron-dependent DNA damage.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

两名晚期（尿毒症）婴儿型肾囊性胱氨酸病（INC）的男性患者通过口服还原剂二硫苏糖醇（DTT）进行治疗，剂量不超过每天三次，每次25毫克/千克体重。在两名患者中获得了三个连续观察期：服用巯基（8.5个月）；停用巯基（8-9个月）；再次服用巯基（7个月或更长时间）……虽然化学方法不能可靠地检测和测量生物流体中的DTT，但初步证据表明，口服DTT的患者的尿液中可以检测到氧化DTT的硅基衍生物。这一发现表明巯基被吸收并排出体外。

Two male patients with late stage (uremic) infantile nephropathic cystinosis (INC) were treated by mouth with the reducing agent dithiothreitol (DTT), at doses not exceeding 25 mg/kg body weight three times per day. Three sequential periods of observation were obtained in both patients: on thiol (8.5 months); off thiol (8-9 months); on thiol again (7 months or longer)... Whereas chemical methods are not reliable for detecting and measuring DTT in biologic fluids, preliminary evidence indicates that a silylated derivative of oxidized DTT can be detected in the urine of patients receiving DTT by mouth. This finding suggests that the thiol is absorbed and excreted.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  1,4-二巯基-2,3-丁二醇 在 bis(4-methoxyphenyl)telluride 、 rose bengal 作用下， 以 水 、 异丙醇 为溶剂， 反应 1.0h， 以75%的产率得到trans-1,2-dithiane-4,5-diol
  参考文献：
  名称：

  在光敏条件下硫醇有氧氧化成二芳基碲化物催化的二硫化物

  摘要：

  在光敏化条件下，二芳基碲化物（如二（4-甲氧基苯基）碲化物）可有效催化硫醇的有氧氧化，从而以良好或优异的收率得到相应的二硫化物。在该催化体系中，由碲化物与单线态氧反应产生的碲化物低聚物被认为是活性物质，并且能够氧化4当量的硫醇。

  DOI：

  10.1021/jo200496r
• 作为产物：
  描述：

  trans-1,2-dithiane-4,5-diol 在 C₁₂₀H₁₃₂N₁₂Ru₂S₂⁽⁴⁺⁾*4F₆P^(1-) 、 三乙胺 作用下， 以 乙腈 为溶剂， 生成 1,4-二巯基-2,3-丁二醇
  参考文献：
  名称：

  带有敏化剂-催化剂-敏化剂三重态的电荷累积和多电子光氧化还原化学

  摘要：

  供体-增敏剂-受体化合物中的光诱导电子转移通常导致简单的电子-空穴对，而光氧化还原催化通常依赖于单电子转移（SET）事件。这项工作报告了一个分子三重态，该分子三重态能够在中央二苯并[1,2]二硫氨酸部分上侧接两个外围Ru II光敏剂，从而积累两个电子。在连续照射下，二苯并[1,2]二硫辛的双还原形式与脂族二硫化物底物进行硫醇盐-二硫化物交换，从而在Ru II上与三乙胺发生两次初始SET事件后充当双电子催化剂敏化剂。从光诱导的SET和光驱动的电荷积累到多电子光氧化还原催化，使用相对简单的三单元组将两个独立的SET过程耦合至随后的双电子还原是重要的概念进展。通常，这与人工光合作用和光驱动的多电子化学有关。

  DOI：

  10.1002/chem.201804037
• 作为试剂：
  描述：

  在 pyrophosphatase 、 sesquiterpene cyclase 、 sodium chloride 、 magnesium chloride 、 1,4-二巯基-2,3-丁二醇 作用下， 以 aq. phosphate buffer 为溶剂， 以2.7 mg的产率得到
  参考文献：
  名称：

  倍半萜环化酶 BcBOT2 促进甲氧基前所未有的 Wagner-Meerwein 重排

  摘要：

  Presilphiperfolan-8β-ol 合酶 (BcBOT2) 是一种真菌来源的底物混杂倍半萜环化酶 (STC)，能够转化两种新的法呢基焦磷酸 (FPP) 衍生物，这些衍生物在法呢基焦磷酸 (FPP) 的 C7 处修饰，带有羟甲基或甲氧基甲基。这些基材是根据计算生成的模型选择的。生物转化产生了五种新的含氧萜类化合物。值得注意的是，这些三环产物之一的形成只能通过阳离子诱导的甲氧基迁移来解释，可能是通过梅尔文盐中间体，这在合成化学和生物合成中是前所未有的。结果显示了萜烯环化酶对于异常阳离子化学的机理研究和创建新萜烯骨架的重要原理和普遍潜力。

  DOI：

  10.1021/jacs.4c03386

文献信息

• Insertion of ethyl diazoacetate into N–H and S–H bonds catalyzed by ruthenium porphyrin complexes
  作者：Erwan Galardon、Paul Le Maux、Gérard Simonneaux

  DOI：10.1039/a704687a

  日期：——

  Ruthenium porphyrin complexes catalyze insertion of ethyl diazoacetate into sulfur–hydrogen and nitrogen–hydrogen bonds under mild conditions and with reasonable to very good yields.

  钌卟啉配合物可在温和条件下催化乙基重氮乙酸酯插入硫－氢键和氮－氢键，并获得合理的至优良的产率。
• Chemistry of the 8-Nitroguanine DNA Lesion: Reactivity, Labelling and Repair
  作者：Katie J. Alexander、Matthew McConville、Kathryn R. Williams、Konstantin V. Luzyanin、Ian A. O'Neil、Richard Cosstick

  DOI：10.1002/chem.201705541

  日期：2018.2.26

  nucleotides, despite the fact that their biological effects are closely linked to their chemical properties. To this end, a selection of chemical reactions have been performed on 8‐nitroguanine nucleosides and oligodeoxynucleotides. Reactions with alkylating reagents reveal how the 8‐nitro substituent affects the reactivity of the purine ring, by significantly decreasing the reactivity of the N2 position

  DNA中的8-硝基鸟嘌呤损伤越来越多地与炎症相关的癌变相关，而鸟苷3'，5'-环一磷酸的相同修饰在NO介导的信号转导中产生了第二个信使。尽管关于8-硝基鸟嘌呤核苷酸的生物学效应与其化学性质紧密相关，但对8-硝基鸟嘌呤核苷酸的化学知之甚少。为此，已对8-硝基鸟嘌呤核苷和寡脱氧核苷酸进行了化学反应选择。与烷基化试剂的反应揭示了8-硝基取代基如何通过显着降低N 2位置的反应性以及同时在N处的相对反应性而影响嘌呤环的反应性1似乎被增强。有趣的是，用硫醇置换硝基导致了标记该病灶的有效且特异性的方法，并在寡聚脱氧核苷酸中得到证实。另外，通过使用氢化物​​源的还原性脱硝作用，该病变的修复也被证明是化学上可行的反应。
• Novel functionalized organotellurides with enhanced thiol peroxidase catalytic activity
  作者：Damiano Tanini、Anna Grechi、Lorenzo Ricci、Silvia Dei、Elisabetta Teodori、Antonella Capperucci

  DOI：10.1039/c8nj00700d

  日期：——

  The thiol peroxidase-like activity of a series of novel functionalized tellurium containing catalysts has been investigated with different models. Dialkyl- and aryl-alkyl-tellurides, conveniently achieved through the ring opening of strained heterocycles, exhibited remarkable catalytic antioxidant activity, being able to reduce hydrogen peroxide in the presence of different thiols (benzenethiol, dithiothreitol

  已经用不同的模型研究了一系列新型的功能化的含碲催化剂的硫醇过氧化物酶样活性。通过紧张的杂环的开环方便地获得的二烷基-和芳基-烷基-碲化物，表现出显着的催化抗氧化活性，能够在不同条件下在不同硫醇（苯硫醇，二硫苏糖醇和谷胱甘肽）存在下还原过氧化氢。β-取代基的性质极大地影响了所研究催化剂的性能，从而为设计谷胱甘肽过氧化物酶的良好合成模拟物提供了有用的标准。已将官能化的有机碲化物与其硒化类似物的催化活性进行了比较，显示后者的催化活性较低。
• Compounds that modulate PPAR activity and methods of preparation
  申请人：——

  公开号：US20030207916A1

  公开（公告）日：2003-11-06

  This invention discloses compounds that alter PPAR activity. The invention also discloses pharmaceutically acceptable salts of the compounds, pharmaceutically acceptable compositions comprising the compounds or their salts, and methods of using them as therapeutic agents for treating or preventing hyperlipidemia and hypercholesteremia in a mammal. The present invention also discloses method for making the disclosed compounds.

  这项发明揭示了能够改变PPAR活性的化合物。该发明还揭示了这些化合物的药用盐、包含这些化合物或其盐的药用组合物，以及将它们用作治疗或预防哺乳动物高脂血症和高胆固醇血症的治疗剂的方法。本发明还揭示了制备所述化合物的方法。
• Oxidation of thiols to disulfides with molecular bromine on hydrated silica gel support
  作者：Mohammed Hashmat Ali、Mario McDermott

  DOI：10.1016/s0040-4039(02)01220-0

  日期：2002.8

  Results of oxidation of thiols to disulfides with molecular bromine on silica gel solid support are reported. The procedure utilizes organic media and does not require a base to neutralize HBr by-products to suppress acid promoted side reactions. Utilization of silica gel support simplifies work up and product isolation.

  报道了在硅胶固体载体上用分子溴将硫醇氧化为二硫化物的结果。该方法利用有机介质，不需要碱来中和HBr副产物以抑制酸促进的副反应。硅胶载体的使用简化了后处理和产品分离。

表征谱图