N,N-dimethyldithiocarbamate | 7234-39-1

• 分子结构分类: 有机化合物 - 有机硫化合物
• 英文名称: N,N-dimethyldithiocarbamate
• 英文别名: dimethyldithiocarbamate；N,N-dimethylcarbamodithioate
• CAS: 7234-39-1
• 化学式: C₃H₆NS₂
• 分子量: 120.219
• InChiKey: MZGNSEAPZQGJRB-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

水溶性代谢物的存在表明在摄入Ziram后胃中产生了二甲二硫代氨基甲酸酯离子。

PRESENCE OF WATER SOL METABOLITES INDICATES GENERATION OF DIMETHYLDITHIOCARBAMATE ION IN STOMACH AFTER INGESTION OF ZIRAM ... .

来源:Hazardous Substances Data Bank (HSDB)

代谢

在口服[35]S ziram后，大鼠通过粪便排出了部分物质（主要是氯仿可溶形式），但绝大多数以水溶性代谢物的形式通过尿液排出。24小时后，组织中只剩下少量的浓度，主要是水溶性形式。除了ziram之外，通过纸层析法还区分出了五种氯仿可溶代谢物和五种水溶性代谢物。在粪便中，57%的氯仿可溶活性是未改变的ziram。这五种氯仿可溶代谢物在胃内容物中找到，以及其他位置，这表明但肯定没有证明ziram的部分分解发生在吸收之前。

Following oral admin of [35]S ziram, rats eliminated a portion in the feces (largely in chloroform-soluble form) but by far the majority was excreted in the urine as water-soluble metabolites. After 24 hrs only small concns, mainly in water-soluble form, remained in the tissues. In addn to ziram, five chloroform-soluble metabolites & five water-soluble metabolites were distinguished by paper chromatography. In the feces, 57% of the chloroform-soluble activity was unchanged ziram. The five chloroform-soluble metabolites were found in the gastric contents, among other locations, suggesting but certainly not proving that part of the breakdown of ziram occurs before absorption.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠研究中，证实了ziram产生了二甲基二硫代氨基甲酸、二甲胺和二硫化碳，以及两种不含锌但含有四个甲基基团的化合物...

In studies of ziram in rats, ... production of dimethyldithiocarbamic acid, dimethylamine, and carbon disulfide /was confirmed, as well as/ ... two compounds that lacked zinc but contained four methyl groups...

来源:Hazardous Substances Data Bank (HSDB)

代谢

水溶性代谢物在大鼠口服放射性标记的Ziram后24小时内在血液、肾脏、肝脏、卵巢、脾脏和甲状腺中被发现；未改变的Ziram通过粪便排出。

Water-soluble metabolites were found in the blood, kidneys, liver, ovaries, spleen and thyroid of female rats 24 hrs after oral administration of radiolabelled ziram; unchanged ziram was excreted in the feces.

来源:Hazardous Substances Data Bank (HSDB)

代谢

植物中的主要代谢物是二甲胺基盐的二甲基二硫代氨基甲酸；也可以形成四甲基硫脲、二硫化碳和硫。二甲基二硫代氨基甲酸可以以DDC-α-氨基丁酸和DDC-α-丙氨酸的形式存在。

The major metabolite in plants is dimethylamine salt of dimethyldithiocarbamic acid; tetramethylthiourea, carbon disulfide, and sulfur can also be formed. Dimethyldithiocarbamic acid can be present as DDC-alpha-aminobutyric acid & DDC-alpha-alanine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：有致癌性的提示性证据，但不足以评估对人类致癌的可能性；可能对人类具有致癌性。

Cancer Classification: Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic Potential; Likely to be Carcinogenic to Humans

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：没有来自人类研究的资料。在实验动物中，对齐拉姆（ziram）致癌性的证据有限。总体评估：齐拉姆对人类致癌性不可分类（第3组）。

Evaluation: No data were available from studies in humans. There is limited evidence in experimental animals for the carcinogenicity of ziram. Overall evaluation: Ziram 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：眯唑姆

IARC Carcinogenic Agent:Ziram

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)

吸收、分配和排泄

口服剂量在无油的情况下吸收不良。可能会通过完好皮肤吸收。

ORAL DOSES POORLY ABSORBED IN ABSENCE OF OILS. MAY BE ABSORBED THROUGH INTACT SKIN.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给予雌性大鼠口服放射性标记的福美锌24小时后，在大鼠的血液、肾脏、肝脏、卵巢、脾脏和甲状腺中发现了水溶性代谢物；未改变的福美锌随粪便排出。

Water soluble metabolites were found in the blood, kidneys, liver, ovaries, spleen, and thyroid of female rats 24 hr after oral administration of radiolabelled ziram; unchanged ziram was excreted in the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

短期内静态生物积累实验中...二甲基二硫代氨基甲酸锌（ziram）...迅速通过组织传播。全身积累较低，生物浓缩因子小于100。全身消除迅速，45%...的初始放射性...在16天的排泄期结束时被保留。色素沉着组织也似乎是主要的分布地点。这可能与这种化合物及其降解产物对黑色素或与含铜的酪氨酸酶复合物的亲和力有关。放射自显影还揭示了甲状腺滤泡的高度标记。结果表明，二硫代氨基甲酸盐在各种组织中具有选择性定位，据报道，这些组织是其毒性作用的目标器官。

In short term static bioaccumulation experiments... zinc dimethyldithiocarbamate (ziram).../was/ rapidly disseminated through the tissues. Whole body accumulation was low, with bioconcentration factors <100. Whole body elimination was rapid with 45%...of the initial radioactivity ...being retained by the end of the 16 day depuration period. Pigmented tissues appeared to be major distribution sites as well. This may be related to the affinity of /this compound/ and/or /its/ degradation products to melanin or to complexation with phenoloxidase, a copper containing enzyme involved in melanin synthesis. Autoradiography also revealed a high labelling of thyroid follicles. The results show that dithiocarbamates are selectively localized in various tissues, reported to be the target organs for their toxic actions.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

这一事实表明，IP毒性显著更高，说明口服剂量的吸收相对较慢和/或不完全。

The fact that the ip toxicity is substantially greater suggests that absorption of an oral dose is relatively slow &/or incomplete.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在饮食中添加了2500 ppm的ziram两年的老鼠，肝脏中该化合物的浓度大约为4 ppm。因此，一个每天大约接收30毫克，持续了两年的动物，其肝脏中该物质的含量最多只有0.03毫克。相反，储存在骨骼中的锌含量几乎以线性方式增加，与饮食中ziram的浓度对数相对应，平均值从180-300 ppm增加到骨骼灰分中的锌，分别对应于在含有0和2500 ppm的ziram的饮食中维持了两年的动物。因此，ziram本身不被储存，但从它代谢出来的锌在一定程度上被储存。

Rats that had received ziram at a dietary level of 2500 ppm for 2 yrs had a concn of about 4 ppm of the compound in the liver. Thus an animal that received about 30 mg/day for 2 yrs had at most only 0.03 mg of the substance in its liver. On the contrary, the concn of zinc stored in bone increased in an almost linear fashion corresponding to the logarithm of the concn of ziram in the diet, the means increasing from 180-300 ppm of zinc in bone ash in animals maintained for 2 yrs on diets containing 0 & 2500 ppm of ziram, respectively. Thus, ziram is not stored but the zinc metabolized from it is stored to a slight degree.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  N,N-dimethyldithiocarbamate 在 氯胺 作用下， 以 phosphate buffer 为溶剂， 反应 240.0h， 生成 亚硝基二甲胺
  参考文献：
  名称：

  Characterization and Fate of N-Nitrosodimethylamine Precursors in Municipal Wastewater Treatment Plants

  摘要：

  The potent carcinogen, N-nitrosodimethylamine (NDMA), is produced during disinfection of municipal wastewater effluent from the reaction of monochloramine and organic nitrogen-containing precursors. To delineate the sources and fate of NDMA precursors during municipal wastewater treatment, NDMA formation was measured after extended chloramination of both model precursors and samples from conventional and advanced wastewater treatment plants. Of the model precursors, only dimethylamine, tertiary amines with dimethylamine functional groups, and dimethylamides formed significant NDMA concentrations upon chloramination. In samples from municipal wastewater treatment plants, dissolved NDMA precursors always were present in primary and secondary effluents. Biological treatment effectively removed the known NDMA precursor dimethylamine, lowering its concentration to levels that could not produce significant quantities of NDMA upon chlorine disinfection. However, biological treatment was less effective at removing other dissolved NDMA precursors, even after extended biological treatment. Significant concentrations of particle-associated NDMA precursors only were detected in secondary effluent at treatment plants that recycled water from sludge thickening operations in which dimethylamine-based synthetic polymers were used. Effective strategies for the prevention of NDMA formation during wastewater chlorination include ammonia removal by nitrification to preclude chloramine formation during chlorine disinfection, elimination of dimethylamine-based polymers, and use of filtration and reverse osmosis to remove particle-associated precursors and dissolved precursors, respectively.

  DOI：

  10.1021/es035025n
• 作为产物：
  描述：

  二甲胺 生成 N,N-dimethyldithiocarbamate
  参考文献：
  名称：

  TAGASHIRA, SHOJI;SASAKI, YOSHIAKI;HAYASHI, KENJIRO;FUKUHARA, GENJI, ANAL. CHIM. ACTA, 244,(1991) N, C. 239-243

  摘要：

  DOI：

文献信息

• Photochemical ligand loss as a basis for imaging and microstructure formation in a thin polymeric film
  作者：Sharon Gould、Terrence R. O'Toole、Thomas J. Meyer

  DOI：10.1021/ja00182a007

  日期：1990.12

  occurs in thin polymeric films of poly(Ru(bpy)sub 2}(vpy)sub 2})sup 2+} (bpy is 2,2prime}-bipyridine, vpy is 4-vinylpyridine), poly(Ru(Mesub 2}bpy)sub 2}(vpy)sub 2})sup 2+} (Mesub 2}bpy is 4,4prime}-dimethyl-2,2prime}-bipyridine), and poly(Ru(Mesub 4}bpy)sub 2}(vpy)sub 2})sup 2+} (Mesub 4}bpy is 4,4prime},5,5prime}-tetramethyl-2,2prime}-bipyridine). These films were formed by reductive

  配体损失光化学发生在聚 (Ru(bpy)sub 2}(vpy)sub 2})sup 2+}（bpy 是 2,2prime}-联吡啶，vpy 是 4-乙烯基吡啶）的聚合物薄膜中, poly(Ru(Mesub 2}bpy)sub 2}(vpy)sub 2})sup 2+} (Mesub 2}bpy 是 4,4prime}-二甲基-2,2素}-联吡啶）和聚（Ru（Mesub 4}bpy）sub 2}（vpy）sub 2}）sup 2+}（Mesub 4}bpy 是 4,4prime}， 5,5prime}-四甲基-2,2prime}-联吡啶）。这些薄膜是通过相应的 4-乙烯基吡啶配合物在 Pt 圆盘电极上的还原电聚合形成的。光解后，钌-吡啶键断裂，聚合物丢失，暴露出下面的基材。通过使用掩蔽技术，使用光化学反应将图像转移到薄膜上。在随后的步骤中，poly(Os(vbpy)sub
• Inclusion Complexes of Gold(I)‐Dithiocarbamates with β‐Cyclodextrin: A Journey from Drug Repurposing towards Drug Discovery
  作者：Michael Morgen、Piotr Fabrowski、Eberhard Amtmann、Nikolas Gunkel、Aubry K. Miller

  DOI：10.1002/chem.202101366

  日期：2021.8.19

  The gold(I)-dithiocarbamate (dtc) complex [Au(N,N-diethyl)dtc]2 was identified as the active cytotoxic agent in the combination treatment of sodium aurothiomalate and disulfiram on a panel of cancer cell lines. In addition to demonstrating pronounced differential cytotoxicity to these cell lines, the gold complex showed no cross-resistance in therapy-surviving cancer cells. In the course of a medicinal

  金(I)-二硫代氨基甲酸盐 (dtc) 复合物 [Au( N , N-二乙基)dtc] 2被确定为金硫苹果酸钠和双硫仑联合治疗一组癌细胞系的活性细胞毒剂。除了对这些细胞系表现出明显的差异细胞毒性外，金复合物在治疗后存活的癌细胞中没有表现出交叉耐药性。在针对此类难溶性金 (I)-dtc 配合物开展的药物化学研究过程中，合成了超过 35 种衍生物，并使用 X 射线晶体学检查了 dtc 部分的结构。一组羟基取代的配合物具有改善的溶解度，并且发现这些配合物与β-环糊精（CD）形成2：1的主客体包合配合物，表现出罕见的“尾对尾”排列CD锥体。羟基取代的金 (I)-dtc 复合物与过量的磺丁基醚-β-CD 的配制可防止线粒体活性氧的诱导，而线粒体活性氧是金属药物开发中的主要负担。
• Trimethylplatinum(IV) complexes of dithiocarbamato ligands: an experimental NMR study on the barrier to C–N bond rotation
  作者：Peter J. Heard、Kenneth Kite、Julie Søgaard Nielsen、Derek A. Tocher

  DOI：10.1039/b000264j

  日期：——

  The trimethylplatinum(IV) complexes of a number of dithiocarbamato ligands have been prepared. The complexes are dimeric in the solid state and in solution, with the ligands acting in both a bridging and chelating fashion. Restricted rotation about the ligand C–N bonds in solution leads to the formation of four rotomers. The kinetics of the restricted rotation was measured by a variety of dynamic NMR techniques in the slow and intermediate exchange regimes. Two distinct processes are observed, namely the independent rotation about each C–N bond and correlated rotation about both C–N bonds. The free energies of activation, which are strongly dependent on the nature of the ligand substituents, are in the range 65–88 kJ mol−1 at 298 K. The origins of the barrier to rotation and the effects of the nitrogen substituents are discussed. The crystal structures of fac-[PtMe3(Me2NCS2)]2 and fac-[PtMe3(Ph(H)NCS2)]2 are reported.

  已经制备了许多二硫代氨基甲酸酯配体的三甲基铂(IV)络合物。该复合物在固态和溶液中都是二聚体，配体以桥联和螯合方式起作用。溶液中配体 C−N 键的受限旋转导致形成四个旋转异构体。通过多种动态核磁共振技术在慢速和中间交换状态下测量受限旋转的动力学。观察到两个不同的过程，即围绕每个 C-N 键的独立旋转和围绕两个 C-N 键的相关旋转。活化自由能很大程度上取决于配体取代基的性质，在 298 K 时范围为 65–88 kJ mol–1。旋转势垒的起源和氮取代基的影响为讨论过。报道了 fac-[PtMe3(Me2NCS2)]2 和 fac-[PtMe3(Ph(H)NCS2)]2 的晶体结构。
• Synthesis, molecular structure, and voltammetric behaviour of unusually stable cis-dioxobis(diisobutyldithiocarbamato)tungsten(VI)
  作者：Kei Unoura、Mitsuru Kondo、Akira Nagasawa、Masatoshi Kanesato、Hiroshi Sakiyama、Aiko Oyama、Hiroaki Horiuchi、Eri Nishida、Takuya Kondo

  DOI：10.1016/j.ica.2003.10.005

  日期：2004.3

  of cis -dioxotungsten(VI) complexes. The structural features of [WO 2 ( i -Bu 2 dtc) 2 ] are very similar to those of corresponding cis -dioxomolybdenum(VI) analogues. The complex [WO 2 ( i -Bu 2 dtc) 2 ] undergoes one-electron quasi-reversible reduction followed by a homogeneous chemical reaction at more negative potential (−1.40 V vs. SSCE) than the corresponding molybdenum analogue [MoO 2 ( i -Bu

  通过空气中WO 4 2-和i -Bu 2 dtc-的反应合成了异常稳定的顺式-二氧双（二异丁基二硫代氨基甲酸酯）钨（VI）[WO 2（i -Bu 2 dtc）2]。报道了该配合物的X射线晶体结构和伏安行为。配合物的WO 2 S 4核的几何形状是八面体形，两个顺式末端的氧代配体相互错位。配合物的平均W = O距离为1.719 A，键合键的键角为104.7°，在顺式-二氧钨钨（VI）配合物的范围内。[WO 2（i -Bu 2 dtc）2]的结构特征与相应的顺式-二氧钼钼（VI）类似物的结构特征非常相似。
• Cancer cell-selective modulation of mitochondrial respiration and metabolism by potent organogold(<scp>iii</scp>) dithiocarbamates
  作者：Randall T. Mertens、Sean Parkin、Samuel G. Awuah

  DOI：10.1039/d0sc03628e

  日期：——

  targeted therapy remains underexplored. We report the synthesis and characterization of ten (10) novel, highly potent organometallic gold(III) complexes supported by dithiocarbamate ligands as selective inhibitors of mitochondrial respiration. The structure of dithiocarbamates employed dictates the biological stability and cellular cytotoxicity. Most of the compounds exhibit 50% inhibitory concentration (IC50)

  代谢重编程是癌症的一个关键标志，它导致了糖酵解的治疗目标。然而，针对线粒体呼吸功能障碍进行靶向治疗的药物仍未得到充分探索。我们报告了十 (10) 种新型高效有机金属金 ( III ) 配合物的合成和表征，这些配合物由二硫代氨基甲酸酯配体支持，作为线粒体呼吸的选择性抑制剂。所用二硫代氨基甲酸盐的结构决定了生物稳定性和细胞毒性。当在一组侵袭性癌症类型中进行测试时，大多数化合物在低微摩尔 (0.50–2.9 μM) 范围内表现出 50% 抑制浓度 (IC 50 )，并且对癌细胞比正常细胞具有显着选择性。因此，人们对金化疗药物的作用机制非常感兴趣，特别是考虑到 DNA 并不是大多数金复合物的主要靶标。我们研究了代表性复合物1a和2a在顽固性三阴性乳腺癌 (TNBC) 细胞系 MDA-MB-231 中的作用机制。全细胞转录组测序揭示了与三个主要途径相关的基因，即：细胞周期、细胞器裂变和氧化磷酸化。2a不可逆地快速抑制