5-[N-[N',N'-bis(2-pyridinylmethyl)]-2-aminoethyl]amino-2',7'-difluoro-3',6'-dihydroxy-spiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one | 443302-08-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 5-[N-[N',N'-bis(2-pyridinylmethyl)]-2-aminoethyl]amino-2',7'-difluoro-3',6'-dihydroxy-spiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one
• 英文别名: 5-[2-[Bis(pyridin-2-ylmethyl)amino]ethylamino]-2-(2,7-difluoro-3-hydroxy-6-oxoxanthen-9-yl)benzoic acid
• CAS: 443302-08-7
• 化学式: C₃₄H₂₆F₂N₄O₅
• 分子量: 608.601
• InChiKey: PUDBCJSXTISPOO-UHFFFAOYSA-N

物化性质

• 沸点：
  805.2±65.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  二甲基吡啶胺 在 氢氧化钾 、 potassium carbonate 、 苯硫酚 、 potassium iodide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.0h， 生成 5-[N-[N',N'-bis(2-pyridinylmethyl)]-2-aminoethyl]amino-2',7'-difluoro-3',6'-dihydroxy-spiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one
  参考文献：
  名称：

  Improvement and Biological Applications of Fluorescent Probes for Zinc, ZnAFs

  摘要：

  The development and cellular applications of novel fluorescent probes for Zn2+, ZnAF-1F, and ZnAF-2F are described. Fluorescein is used as a fluorophore of ZnAFs, because its excitation and emission wavelengths are in the visible range, which minimizes cell damage and autofluorescence by excitation light. N,N-Bis(2-pyridylmethyl)ethylenediamine, used as an acceptor for Zn2+, is attached directly to the benzoic acid moiety of fluorescein, resulting in very low quantum yields of 0.004 for ZnAF-1F and 0.006 for ZnAF-2F under physiological conditions (pH 7.4) due to the photoinduced electron-transfer mechanism. Upon the addition of Zn2+, the fluorescence intensity is quickly increased up to 69-fold for ZnAF-1F and 60-fold for ZnAF-2F. Apparent dissociation constants (K-d) are in the nanomolar range, which affords sufficient sensitivity for biological applications. ZnAFs do not fluoresce in the presence of other biologically important cations such as Ca2+ and Mg2+, and are insensitive to change of pH. The complexes with Zn2+ of previously developed ZnAFs, ZnAF-1, and ZnAF-2 decrease in fluorescence intensity below pH 7.0 owing to protonation of the phenolic hydroxyl group of fluorescein, whose pK(a) value is 6.2. On the other hand, the Zn2+ complexes of ZnAF-1 F and ZnAF-2F emit stable fluorescence around neutral and slightly acidic conditions because the pKa values are shifted to 4.9 by substitution of electron-withdrawing fluorine at the ortho position of the phenolic hydroxyl group. For application to living cells, the diacetyl derivative of ZnAF-2F, ZnAF-2F DA, was synthesized. ZnAF-2F DA can permeate through the cell membrane, and is hydrolyzed by esterase in the cytosol to yield ZnAF-2F, which is retained in the cells. Using ZnAF-2F DA, we could measure the changes of intracellular Zn2+ in cultured cells and hippocampal slices.

  DOI：

  10.1021/ja025567p

文献信息

• Improvement and Biological Applications of Fluorescent Probes for Zinc, ZnAFs
  作者：Tomoya Hirano、Kazuya Kikuchi、Yasuteru Urano、Tetsuo Nagano

  DOI：10.1021/ja025567p

  日期：2002.6.1

  The development and cellular applications of novel fluorescent probes for Zn2+, ZnAF-1F, and ZnAF-2F are described. Fluorescein is used as a fluorophore of ZnAFs, because its excitation and emission wavelengths are in the visible range, which minimizes cell damage and autofluorescence by excitation light. N,N-Bis(2-pyridylmethyl)ethylenediamine, used as an acceptor for Zn2+, is attached directly to the benzoic acid moiety of fluorescein, resulting in very low quantum yields of 0.004 for ZnAF-1F and 0.006 for ZnAF-2F under physiological conditions (pH 7.4) due to the photoinduced electron-transfer mechanism. Upon the addition of Zn2+, the fluorescence intensity is quickly increased up to 69-fold for ZnAF-1F and 60-fold for ZnAF-2F. Apparent dissociation constants (K-d) are in the nanomolar range, which affords sufficient sensitivity for biological applications. ZnAFs do not fluoresce in the presence of other biologically important cations such as Ca2+ and Mg2+, and are insensitive to change of pH. The complexes with Zn2+ of previously developed ZnAFs, ZnAF-1, and ZnAF-2 decrease in fluorescence intensity below pH 7.0 owing to protonation of the phenolic hydroxyl group of fluorescein, whose pK(a) value is 6.2. On the other hand, the Zn2+ complexes of ZnAF-1 F and ZnAF-2F emit stable fluorescence around neutral and slightly acidic conditions because the pKa values are shifted to 4.9 by substitution of electron-withdrawing fluorine at the ortho position of the phenolic hydroxyl group. For application to living cells, the diacetyl derivative of ZnAF-2F, ZnAF-2F DA, was synthesized. ZnAF-2F DA can permeate through the cell membrane, and is hydrolyzed by esterase in the cytosol to yield ZnAF-2F, which is retained in the cells. Using ZnAF-2F DA, we could measure the changes of intracellular Zn2+ in cultured cells and hippocampal slices.