1,1'-((2-(phenylthio)phenyl)methylene)bis(3,5-dimethyl-1H-pyrazole) | 1292840-71-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 1,1'-((2-(phenylthio)phenyl)methylene)bis(3,5-dimethyl-1H-pyrazole)
• 英文别名: ((2-(phenylthio)phenyl)methylene)bis(3,5-dimethyl-1H-pyrazole)；PhSC6H4CH(C3HN2(Me)2)2；1-[(3,5-Dimethylpyrazol-1-yl)-(2-phenylsulfanylphenyl)methyl]-3,5-dimethylpyrazole；1-[(3,5-dimethylpyrazol-1-yl)-(2-phenylsulfanylphenyl)methyl]-3,5-dimethylpyrazole
• CAS: 1292840-71-1
• 化学式: C₂₃H₂₄N₄S
• 分子量: 388.536
• InChiKey: MFNYVPYZMNZUSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  60.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  copper(II) choride dihydrate 、 1,1'-((2-(phenylthio)phenyl)methylene)bis(3,5-dimethyl-1H-pyrazole) 以 甲醇 为溶剂， 生成 [Cu2Cl3(PhSC6H4CH(C3HN2(Me)2)2-N,N')]Cl*1.25water
  参考文献：
  名称：

  Copper Binding Agents Acting as Copper Ionophores Lead to Caspase Inhibition and Paraptotic Cell Death in Human Cancer Cells

  摘要：

  We report a quantitative structure activity relationship study of a new class of pyrazole-pyridine copper complexes that establishes a clear correlation between the ability to promote copper accumulation and cytotoxicity. Intracellular metal accumulation is maximized when ligand lipophilicity allows the complex to rapidly cross the membrane. Copper and ligand follow different uptake kinetics and reach different intracellular equilibrium concentrations. These results support a model in which the ligand acts as an ionophore for the metal ion, cycling between intra- and extracellular compartments as dissociated or complexed entities. When treating cancer cells with structurally unrelated disulfiram and pyrazole-pyridine copper complexes, as well as with inorganic copper, the same morphological and molecular changes were reproduced, indicating that copper overload is responsible for the cytotoxic effects. Copper-based treatments drive sensitive cancer cells toward paraptotic cell death, a process hallmarked by endoplasmic reticulum stress and massive vacuolization in the absence of apoptotic features. A lack of caspase activation, as observed in copper-treated dying cells, is a consequence of metal-mediated inhibition of caspase-3. Thus, copper acts simultaneously as an endoplasmic reticulum (ER) stress inducer and a caspase-3 inhibitor, forcing the cell into caspase-independent paraptotic death. The establishment of a mechanism of action common to different copper binding agents provides a rationale for the exploitation of copper toxicity as an anticancer tool.

  DOI：

  10.1021/ja109413c
• 作为产物：
  描述：

  2-(苯硫基)苯甲醛 、 双(3,5-二甲基吡唑-1-基)甲酮 在 cobalt(II) chloride 作用下， 生成 1,1'-((2-(phenylthio)phenyl)methylene)bis(3,5-dimethyl-1H-pyrazole)
  参考文献：
  名称：

  Influence of Anions in Silver Supramolecular Frameworks: Structural Characteristics and Sorption Properties.

  摘要：

  The complexation of a preorganized thioether-functionalized bis(pyrazoly)methane ligand (L) with silver precursors produces supramolecular structures organized at two hierarchical levels: [AgL](6)(X)(6) metal-organic cyclic hexamers and their organization in 3D architectures. The cyclic toroidal hexamers of 22-26 angstrom external diameter are found to be stable already in solution before self-assembly into the crystalline state. In the 3D lattice, the hexameric building block are arranged in different highly symmetric space groups as a function of a variety of anions (cubic Fd $(3) over bar $ with PF6- or BF4- and rhombohedral R $(3) over bar $ with CF3SO3- or NO3-) and form cavities with the geometrical shapes of Platonic solids (tetrahedron and octahedron) that can be occupied by a variety of solvent molecules. Upon evacuation, cubic crystals can produce stable frameworks with permanent porosity, which can absorb reversibly several vapors, CO2 and CH4.

  DOI：

  10.1021/ja303940d

文献信息

• Copper Binding Agents Acting as Copper Ionophores Lead to Caspase Inhibition and Paraptotic Cell Death in Human Cancer Cells
  作者：Saverio Tardito、Irene Bassanetti、Chiara Bignardi、Lisa Elviri、Matteo Tegoni、Claudio Mucchino、Ovidio Bussolati、Renata Franchi-Gazzola、Luciano Marchiò

  DOI：10.1021/ja109413c

  日期：2011.4.27

  We report a quantitative structure activity relationship study of a new class of pyrazole-pyridine copper complexes that establishes a clear correlation between the ability to promote copper accumulation and cytotoxicity. Intracellular metal accumulation is maximized when ligand lipophilicity allows the complex to rapidly cross the membrane. Copper and ligand follow different uptake kinetics and reach different intracellular equilibrium concentrations. These results support a model in which the ligand acts as an ionophore for the metal ion, cycling between intra- and extracellular compartments as dissociated or complexed entities. When treating cancer cells with structurally unrelated disulfiram and pyrazole-pyridine copper complexes, as well as with inorganic copper, the same morphological and molecular changes were reproduced, indicating that copper overload is responsible for the cytotoxic effects. Copper-based treatments drive sensitive cancer cells toward paraptotic cell death, a process hallmarked by endoplasmic reticulum stress and massive vacuolization in the absence of apoptotic features. A lack of caspase activation, as observed in copper-treated dying cells, is a consequence of metal-mediated inhibition of caspase-3. Thus, copper acts simultaneously as an endoplasmic reticulum (ER) stress inducer and a caspase-3 inhibitor, forcing the cell into caspase-independent paraptotic death. The establishment of a mechanism of action common to different copper binding agents provides a rationale for the exploitation of copper toxicity as an anticancer tool.
• Influence of Anions in Silver Supramolecular Frameworks: Structural Characteristics and Sorption Properties.
  作者：Irene Bassanetti、Francesco Mezzadri、Angiolina Comotti、Piero Sozzani、Marcello Gennari、Gianluca Calestani、Luciano Marchiò

  DOI：10.1021/ja303940d

  日期：2012.6.6

  The complexation of a preorganized thioether-functionalized bis(pyrazoly)methane ligand (L) with silver precursors produces supramolecular structures organized at two hierarchical levels: [AgL](6)(X)(6) metal-organic cyclic hexamers and their organization in 3D architectures. The cyclic toroidal hexamers of 22-26 angstrom external diameter are found to be stable already in solution before self-assembly into the crystalline state. In the 3D lattice, the hexameric building block are arranged in different highly symmetric space groups as a function of a variety of anions (cubic Fd $(3) over bar $ with PF6- or BF4- and rhombohedral R $(3) over bar $ with CF3SO3- or NO3-) and form cavities with the geometrical shapes of Platonic solids (tetrahedron and octahedron) that can be occupied by a variety of solvent molecules. Upon evacuation, cubic crystals can produce stable frameworks with permanent porosity, which can absorb reversibly several vapors, CO2 and CH4.