4,5-[(3,5-bismethoxycarbonyl)phenoxy]phthalonitrile | 794518-55-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4,5-[(3,5-bismethoxycarbonyl)phenoxy]phthalonitrile
• 英文别名: Dimethyl 5-[2-[3,5-bis(methoxycarbonyl)phenoxy]-4,5-dicyanophenoxy]benzene-1,3-dicarboxylate；dimethyl 5-[2-[3,5-bis(methoxycarbonyl)phenoxy]-4,5-dicyanophenoxy]benzene-1,3-dicarboxylate
• CAS: 794518-55-1
• 化学式: C₂₈H₂₀N₂O₁₀
• 分子量: 544.474
• InChiKey: LVPXVVBDDKGPAT-UHFFFAOYSA-N

物化性质

• 沸点：
  678.3±55.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  171
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  4,5-[(3,5-bismethoxycarbonyl)phenoxy]phthalonitrile 在 lithium 作用下， 以 戊醇 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and in vitro photodynamic activity of new hexadeca-carboxy phthalocyanines

  摘要：

  我们合成了两种新的十六碳羰基酞菁，并对其光动力活性进行了评估；锌（II）类似物对 J774 鼠巨噬细胞系表现出高度的 A 类清道夫受体介导的光毒性。

  DOI：

  10.1039/b405868b
• 作为产物：
  描述：

  5-羟基间苯二甲酸二甲酯 、 4,5-二氯邻苯二甲腈 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以34.4%的产率得到4,5-[(3,5-bismethoxycarbonyl)phenoxy]phthalonitrile
  参考文献：
  名称：

  Monomer zinc phthalocyanine/upconversion nanoparticle coated with hyaluronic acid crosslinked gel as NIR light-activated drug for in vitro photodynamic therapy

  摘要：

  基于单体酞菁的近红外触发的癌症靶向纳米系统已经制备，显示出令人满意的体外抗癌活性。

  DOI：

  10.1039/c6dt01929c

文献信息

• A soft supramolecular carrier with enhanced singlet oxygen photosensitizing properties
  作者：Jens Voskuhl、Ulrike Kauscher、Malte Gruener、Hendrik Frisch、Birgit Wibbeling、Cristian A. Strassert、Bart Jan Ravoo

  DOI：10.1039/c2sm27353e

  日期：——

  Herein we report the self-assembly of a supramolecular singlet oxygen photosensitizing system from an adamantane-functionalized, hexaanionic water-soluble zinc(II) phthalocyanine (PC) and β-cyclodextrin vesicles (CDV). Characterisation of the designed PC, which was synthesized by an asymmetric statistical condensation, was carried out by several analytical techniques such as MALDI-HRMS, NMR, IR, UV/vis as well as steady state and time resolved fluorescence spectroscopy. The influence of the docking of the PC to the CDVs on the PC photoluminescence as well as on the singlet oxygen photoproduction quantum yields was investigated. The results indicate that the host–guest interaction of the photosensitizer and the CDVs significantly prevents the formation of inactive aggregates, and enhances the photosensitizing ability of the PC. The supramolecular assembly constitutes a biocompatible photoactive platform for the design of phototherapeutic agents.

  在此，我们报告了一种超分子单态氧光敏系统的自组装，该系统由功能化的金刚烷、六价阴离子水溶性锌(II)酞菁 (PC) 和 β-环糊精囊泡 (CDV) 组成。通过多种分析技术对所设计的 PC 进行了表征，包括 MALDI-HRMS、NMR、IR、UV/vis 以及稳态和时间分辨荧光光谱。研究了 PC 与 CDV 的对接对 PC 光致发光以及单态氧光生产量子的影响。结果表明，光敏剂与 CDV 的主客体相互作用显著抑制了无效聚集体的形成，并增强了 PC 的光敏化能力。这种超分子组装构成了一个生物相容的光活性平台，可用于光疗剂的设计。
• Facile synthesis of pegylated zinc(ii) phthalocyanines via transesterification and their in vitro photodynamic activities
  作者：Ming Bai、Pui-Chi Lo、Jing Ye、Chi Wu、Wing-Ping Fong、Dennis K. P. Ng

  DOI：10.1039/c1ob05955f

  日期：——

  Treatment of 4,5-bis[4-(methoxycarbonyl)phenoxy]phthalonitrile and 4,5-bis[3,5-bis(methoxycarbonyl)phenoxy]phthalonitrile with an excess of 1,3-diiminoisoindoline in the presence of Zn(OAc)2·2H2O and 1,8-diazabicyclo[5.4.0]undec-7-ene in triethylene glycol monomethyl ether or polyethylene glycol monomethyl ether (with an average molecular weight of 550) led to “3 + 1” mixed cyclisation and transesterification in one pot, affording the corresponding di-β-substituted zinc(II) phthalocyanines in 7–23% yield. As shown by absorption spectroscopy, these compounds were essentially non-aggregated in N,N-dimethylformamide and could generate singlet oxygen effectively. The singlet oxygen quantum yields (ΦΔ = 0.53–0.57) were comparable with that of the unsubstituted zinc(II) phthalocyanine (ΦΔ = 0.56). These compounds in Cremophor EL emulsions also exhibited photocytotoxicity against HT29 human colorectal adenocarcinoma and HepG2 human hepatocarcinoma cells with IC50 values in the range of 0.25–3.72 μM. The analogue with four triethylene glycol chains was the most potent photosensitiser and localised preferentially in the mitochondria of HT29 cells. The bis(polyethylene glycol)-counterpart could form surfactant-free nanoparticles both in water and in the culture medium. The hydrodynamic radii, as determined by dynamic laser light scattering, ranged from 6.3 to 79.8 nm depending on the preparation methods and conditions. The photocytotoxicity of these nanoparticles (IC50 = 0.43–0.56 μM) was comparable with that of the Cremophor EL-formulated system (IC50 = 0.34 μM).

  处理4,5-双[4-（甲氧羰基）苯氧]邻苯二腈和4,5-双[3,5-双（甲氧羰基）苯氧]邻苯二腈与过量的1,3-二亚胺异烟胺，在Zn(OAc)2·2H2O和1,8-二氮杂双环[5.4.0]十七烯的存在下，在三乙二醇单甲醚或聚乙烯醇单甲醚（平均分子量为550）中反应，导致“3 + 1”混合环化和转酯化在同一反应皿中进行，得到相应的二β-取代锌(II)酞菁，产率为7-23%。通过吸收光谱表明，这些化合物在N,N-二甲基甲酰胺中基本上没有聚集，并能有效生成单重态氧。单重态氧的量子产率（ΦΔ = 0.53-0.57）与未取代的锌(II)酞菁（ΦΔ = 0.56）相当。这些化合物在Cremophor EL乳液中对HT29人结肠腺癌和HepG2人肝癌细胞表现出光细胞毒性，IC50值范围为0.25-3.72 μM。具有四个三乙二醇链的类似物是最有效的光敏剂，并优先定位于HT29细胞的线粒体。双（聚乙烯醇）相应物可以在水和培养基中形成无表面活性剂的纳米颗粒。根据动态激光散射测定的水动力半径范围从6.3到79.8 nm，取决于制备方法和条件。这些纳米颗粒的光细胞毒性（IC50 = 0.43-0.56 μM）与Cremophor EL配方系统（IC50 = 0.34 μM）相当。
• Monomer zinc phthalocyanine/upconversion nanoparticle coated with hyaluronic acid crosslinked gel as NIR light-activated drug for in vitro photodynamic therapy
  作者：Lin Zhou、Enyi Chen、Weiwei Jin、Yue Wang、Jiahong Zhou、Shaohua Wei

  DOI：10.1039/c6dt01929c

  日期：——

  A monomeric phthalocyanine based NIR-triggered cancer target nanosystem was prepared and showed satisfied in vitro anticancer activity.

  基于单体酞菁的近红外触发的癌症靶向纳米系统已经制备，显示出令人满意的体外抗癌活性。
• Ring‐Shaped <i>J</i> ‐Type and Star‐Shaped <i>H</i> ‐Type Nanostructures of an Unsymmetrical (Phthalocyaninato)zinc Complex
  作者：Naichang Tian、Pan Ma、Quanbo Wang、Xianyao Zhang、Jianzhuang Jiang、Ming Bai

  DOI：10.1002/ejic.201001106

  日期：2011.3

  Unsymmetrical (phthalocyaninato)zinc complex 1 was synthesized by transesterification and self-assembled into ring-shaped nanostructures with J-type aggregation at the chloroform/water interface and into star-shaped nanostructures with H-type aggregation in the chloroform/methanol system, respectively. Its self-assembly properties have been studied by spectroscopic, transmission electron microscopy

  不对称（酞菁）锌配合物1通过酯交换合成，并在氯仿/水界面自组装成具有J型聚集的环状纳米结构，在氯仿/甲醇体系中分别自组装成具有H型聚集的星形纳米结构. 已经通过光谱、透射电子显微镜 (TEM)、扫描电子显微镜 (SEM) 和 X 射线衍射 (XRD) 技术研究了其自组装性能。由于更有效的分子间 π 电子离域，星形纳米结构被发现比环形纳米结构具有更好的半导体性能。
• A carboxylated Zn-phthalocyanine inhibits fibril formation of Alzheimer's amyloid β peptide
  作者：Shatera Tabassum、Abdullah M. Sheikh、Shozo Yano、Takafumi Ikeue、Makoto Handa、Atsushi Nagai

  DOI：10.1111/febs.13151

  日期：2015.2

  Amyloid β (Aβ), a 39–42 amino acid peptide derived from amyloid precursor protein, is deposited as fibrils in Alzheimer's disease brains, and is considered to play a major role in the pathogenesis of the disease. We have investigated the effects of a water‐soluble Zn‐phthalocyanine, ZnPc(COONa)8, a macrocyclic compound with near‐infrared optical properties, on Aβ fibril formation in vitro. A thioflavin T fluorescence assay showed that ZnPc(COONa)8 significantly inhibited Aβ fibril formation, increasing the lag time and dose‐dependently decreasing the plateau level of fibril formation. Moreover, it destabilized pre‐formed Aβ fibrils, resulting in an increase in low‐molecular‐weight species. After fibril formation in the presence of ZnPc(COONa)8, immunoprecipitation of Aβ1‐42 using Aβ‐specific antibody followed by near‐infrared scanning demonstrated binding of ZnPc(COONa)8 to Aβ1‐42. A study using the hydrophobic fluorescent probe 8‐anilino‐1‐naphthalenesulfonic acid showed that ZnPc(COONa)8 decreased the hydrophobicity during Aβ1‐42 fibril formation. CD spectroscopy showed an increase in the α helix structure and a decrease in the β sheet structure of Aβ1‐40 in fibril‐forming buffer containing ZnPc(COONa)8. SDS/PAGE and a dot‐blot immunoassay showed that ZnPc(COONa)8 delayed the disappearance of low‐molecular‐weight species and the appearance of higher‐molecular‐weight oligomeric species of Aβ1‐42. A cell viability assay showed that ZnPc(COONa)8 was not toxic to a neuronal cell line (A1), but instead protected A1 cells against Aβ1‐42‐induced toxicity. Overall, our results indicate that ZnPc(COONa)8 binds to Aβ and decreases the hydrophobicity, and this change is unfavorable for Aβ oligomerization and fibril formation.