2,2,5,5-Tetramethyl-3,4-dithiahexane-1,6-diamine | 58262-78-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 有机二硫化物
• 英文名称: 2,2,5,5-Tetramethyl-3,4-dithiahexane-1,6-diamine
• 英文别名: 2,2′-dithiobis(2-methyl-1-propylamine)；2-[(1-Amino-2-methylpropan-2-yl)disulfanyl]-2-methylpropan-1-amine
• CAS: 58262-78-5
• 化学式: C₈H₂₀N₂S₂
• 分子量: 208.392
• InChiKey: UCPGYYKRVOOSMT-UHFFFAOYSA-N

物化性质

• 沸点：
  290.6±25.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,2,5,5-Tetramethyl-3,4-dithiahexane-1,6-diamine 在 HO₃SC₆H₄SH 作用下， 生成 2-巯基-2-甲基-1-丙胺
  参考文献：
  名称：

  Rate constants and equilibrium constants for thiol-disulfide interchange reactions involving oxidized glutathione

  摘要：

  DOI：

  10.1021/ja00526a042
• 作为产物：
  描述：

  1-氨基-2-甲基丙烷-2-硫醇 在 1,3-二溴-5,5-二甲基海因 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.25h， 生成 2,2,5,5-Tetramethyl-3,4-dithiahexane-1,6-diamine
  参考文献：
  名称：

  Disulfide-functional poly(amido amine)s with tunable degradability for gene delivery

  摘要：

  Controlled degradability in response to the local environment is one of the most effective strategies to achieve spatiotemporal release of genes from a polymeric carrier. Exploiting the differences in reduction potential between the extracellular and intracellular environment, disulfides are frequently incorporated into the backbone of polymeric drug delivery agents to ensure efficient intracellular release of the payload. However, although to a lesser extent, reduction of disulfides may also occur in the extracellular environment and should be prevented to avoid premature release. Accurate control over the stability of disulfide linkages enables the optimization of polymeric carriers for efficient drug delivery. Bioreducible poly(amido amine)s (PAAs) with varying degrees of steric hindrance adjacent to the disulfide bonds (0, 2 or 4 methyl groups) were prepared in order to obtain carriers with controlled stability. The degradation behavior of these PAA-polymers was evaluated under different reducing conditions and their in vitro toxicities and transfection efficiencies were assessed. Degradation of the PAA-based polyplexes consistently required higher reducing strengths as the steric hindrance near the disulfide bonds increased. Polyplexes based on 2-methyl cystamine disulfide based PAA polymer (PAA(2m)) remained stable under extracellular glutathione concentrations (0.001-0.01 mM), while degrading within 1 h under reducing conditions similar to those in the intracellular environment (1- 10 mM glutathione). This polymer exhibited excellent transfection capabilities, with efficiencies up to 90% of transfected cells. PAA(0m) showed slightly reduced transfection properties compared to PAA(2m), likely due to premature degradation. The severely hindered PAA(4m), however, displayed increased toxicity, accompanied by reduced transfection efficiency, as a result of its exceptional stability. These results demonstrate the feasibility of introducing steric hindrance near the disulfide moiety to tune polyplex stability against bioreduction, and showthat PAA(2m) is a promising polymer to be further developed for gene therapy. (C) 2016 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jconrel.2016.08.021

文献信息

• New Thionitrites: Synthesis, Stability, and Nitric Oxide Generation
  作者：Beatrice Roy、A. du Moulinet d'Hardemare、Marc Fontecave

  DOI：10.1021/jo00102a028

  日期：1994.11

  In order to study the influence of substitutions at the alpha and beta carbon atoms on the stability of the S-NO bond, water-soluble thionitrites RSNO have been synthesized by nitrosation of cysteamine and mercaptoethanol derivatives and characterized. H-1 and C-13 NMR spectroscopies have proven to be excellent probes for the nitrosation of thiols. In water, at physiological pH, the compounds decomposed into nitric oxide NO and the corresponding disulfides. The rate at which NO was released was very sensitive to modifications at the alpha and beta carbon atoms. Tertiary thionitrites were more stable than primary thionitrites. The beta-substituents decreased the rates of decomposition in the following order: OH > NHCOCH3 > NH3+. S-Nitrosocysteamine derivatives were greatly stabilized at low pH. The compounds described here might be convenient and useful as vehicles for spontaneous generation of nitric oxide in biological systems, at rates that can be finely tuned and controlled over a wide range.
• Rate constants and equilibrium constants for thiol-disulfide interchange reactions involving oxidized glutathione
  作者：Richard P. Szajewski、George M. Whitesides

  DOI：10.1021/ja00526a042

  日期：1980.3
• Disulfide-functional poly(amido amine)s with tunable degradability for gene delivery
  作者：M. Rachèl Elzes、Niels Akeroyd、Johan F.J. Engbersen、Jos M.J. Paulusse

  DOI：10.1016/j.jconrel.2016.08.021

  日期：2016.12

  Controlled degradability in response to the local environment is one of the most effective strategies to achieve spatiotemporal release of genes from a polymeric carrier. Exploiting the differences in reduction potential between the extracellular and intracellular environment, disulfides are frequently incorporated into the backbone of polymeric drug delivery agents to ensure efficient intracellular release of the payload. However, although to a lesser extent, reduction of disulfides may also occur in the extracellular environment and should be prevented to avoid premature release. Accurate control over the stability of disulfide linkages enables the optimization of polymeric carriers for efficient drug delivery. Bioreducible poly(amido amine)s (PAAs) with varying degrees of steric hindrance adjacent to the disulfide bonds (0, 2 or 4 methyl groups) were prepared in order to obtain carriers with controlled stability. The degradation behavior of these PAA-polymers was evaluated under different reducing conditions and their in vitro toxicities and transfection efficiencies were assessed. Degradation of the PAA-based polyplexes consistently required higher reducing strengths as the steric hindrance near the disulfide bonds increased. Polyplexes based on 2-methyl cystamine disulfide based PAA polymer (PAA(2m)) remained stable under extracellular glutathione concentrations (0.001-0.01 mM), while degrading within 1 h under reducing conditions similar to those in the intracellular environment (1- 10 mM glutathione). This polymer exhibited excellent transfection capabilities, with efficiencies up to 90% of transfected cells. PAA(0m) showed slightly reduced transfection properties compared to PAA(2m), likely due to premature degradation. The severely hindered PAA(4m), however, displayed increased toxicity, accompanied by reduced transfection efficiency, as a result of its exceptional stability. These results demonstrate the feasibility of introducing steric hindrance near the disulfide moiety to tune polyplex stability against bioreduction, and showthat PAA(2m) is a promising polymer to be further developed for gene therapy. (C) 2016 Elsevier B.V. All rights reserved.