N¹-(3-Amino-propyl)-N¹-(3-{{3-[bis-(3-amino-propyl)-amino]-propyl}-[2-(bis-{3-[bis-(3-amino-propyl)-amino]-propyl}-amino)-ethyl]-amino}-propyl)-propane-1,3-diamine | 179125-43-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N¹-(3-Amino-propyl)-N¹-(3-{{3-[bis-(3-amino-propyl)-amino]-propyl}-[2-(bis-{3-[bis-(3-amino-propyl)-amino]-propyl}-amino)-ethyl]-amino}-propyl)-propane-1,3-diamine
• 英文别名: N'-(3-aminopropyl)-N'-[3-[3-[bis(3-aminopropyl)amino]propyl-[2-[bis[3-[bis(3-aminopropyl)amino]propyl]amino]ethyl]amino]propyl]propane-1,3-diamine
• CAS: 179125-43-0
• 化学式: C₃₈H₉₂N₁₄
• 分子量: 745.242
• InChiKey: ZZGDQQREWKSDPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  52
• 可旋转键数：
  43
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  228
• 氢给体数：
  8
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N¹-(3-Amino-propyl)-N¹-(3-{{3-[bis-(3-amino-propyl)-amino]-propyl}-[2-(bis-{3-[bis-(3-amino-propyl)-amino]-propyl}-amino)-ethyl]-amino}-propyl)-propane-1,3-diamine 在 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Glycyrrhizin Conjugated Dendrimer and Multi-Walled Carbon Nanotubes for Liver Specific Delivery of Doxorubicin

  摘要：

  本次研究旨在探讨甘草酸（GL）偶联的树枝状大分子（GL-PPI）和多壁碳纳米管（GL-MWCNTs）对模型抗癌药多柔比星（DOX）肝靶向性的潜力。合成过程通过FTIR、1H-NMR和形态分析得到确认。与母体纳米载体相比，GL-PPI-DOX和GL-MWCNT-DOX的DOX负载量更高（分别为43.02±0.64%和87.26±0.57%）。GL的附着显著降低了DOX的溶血毒性，通过GL-PPI-DOX和GL-MWCNT-DOX分别降低了12.38±1.05%和7.30±0.63%。MTT细胞毒性研究、流式细胞术和细胞形态评估在HepG2细胞中进行。DOX的IC50值从4.19±0.05 μM分别降低到2.0±0.01 μM和2.7±0.03 μM，通过GL-PPI-DOX和GL-MWCNT-DOX实现。流式细胞术和相差显微镜证实，GL偶联制剂在早期凋亡阶段显著吸引了更多的癌细胞。

  DOI：

  10.1166/jnn.2015.9039
• 作为产物：
  描述：

  3,3',3'',3'''-(乙烯二次氮基)四丙腈 在 氢气 作用下， 反应 1.0h， 生成 N¹-(3-Amino-propyl)-N¹-(3-{{3-[bis-(3-amino-propyl)-amino]-propyl}-[2-(bis-{3-[bis-(3-amino-propyl)-amino]-propyl}-amino)-ethyl]-amino}-propyl)-propane-1,3-diamine
  参考文献：
  名称：

  Surface-Engineered Dendrimeric Nanoconjugates for Macrophage-Targeted Delivery of Amphotericin B: Formulation Development andIn VitroandIn VivoEvaluation

  摘要：

  摘要本研究旨在为两性霉素 B（AmB）开发一种优化的树枝状给药系统。研究人员合成了第五代（5.0G）聚丙烯亚胺（PPI）树枝状聚合物，并与甘露糖共轭，利用傅立叶变换红外光谱（FTIR）、1H 核磁共振（1H-NMR）光谱分析和原子力显微镜（AFM）等多种分析技术对其进行了表征。将甘露糖共轭的 5.0G PPI（MPPI）树枝状聚合物载入 AmB，并评估了药物载入效率、体外药物释放曲线、稳定性、对人红细胞的溶血性毒性、对 J774A.1 巨噬细胞的细胞毒性和细胞摄取量、抗寄生虫性和抗药性。巨噬细胞的细胞毒性、对细胞内利什曼原虫的抗寄生活性、体内药代动力学和生物分布曲线、药物定位指数、毒性和抗利什曼活性。原子力显微镜（AFM）显示，MPPI 树枝状聚合物的尺寸为纳米级，结构接近球状。该共轭物对 AmB 有很好的吸附效率，同时还具有对 pH 值敏感的药物释放特性。在不影响 AmB 的抗寄生虫活性的情况下，它对人类红细胞和巨噬细胞的毒性大大降低。AmB 的树枝状聚合物制剂显示，AmB 对巨噬细胞内唐氏原虫的杀寄生虫活性显著增强。在玻璃细胞摄取研究中，该制剂显示出对巨噬细胞的选择性，具有显著的细胞内摄取作用。进一步的药代动力学和器官分布研究阐明了该制剂的控制给药行为。活体研究表明，MPPIA 具有生物相容性，即使剂量较大，毒性也可忽略不计，而且具有良好的抗利什曼病活性。从这些结果中，我们得出结论，表面工程树枝状聚合物可作为 AmB 的优化递送载体，具有更高的活性和低毒性或可忽略不计的毒性。

  DOI：

  10.1128/aac.04213-14

文献信息

• Surface Engineered Dendrimers as Antiangiogenic Agent and Carrier for Anticancer Drug: Dual Attack on Cancer
  作者：K. Jain、N. K. Jain

  DOI：10.1166/jnn.2014.8677

  日期：2014.7.1

  The present research work describes the formulation of arginine conjugated 3.0G Poly(propylene) imine (PPI) dendrimers, mimicking the surface structure of an endogenous angiogenesis-inhibitor endostatin; for tumor specific delivery of a model anticancer drug, doxorubicin hydrochloride (Dox). Synthesis of PPI dendrimers and conjugation of arginine to surface groups was confirmed by FTIR, NMR, TEM and mass spectrometry. Drug was loaded by equilibrium dialysis method and developed formulation was evaluated for entrapment efficiency, hemolytic toxicity, in vitro drug release, stability, anti-angiogenic activity via in vivo chick embryo chorioallantoic membrane (CAM) assay, and anticancer activity and cell uptake using MCF-7 cancer cell lines. The system exhibited the initial rapid release followed by sustained release of Dox with significant antiangiogenic activity in the CAM assay. Further, the arginine conjugated dendrimers was found to inhibit growth of cancer cells in ex vivo studies with MCF-7 cell lines. Cell uptake studies suggested that in comparison to free drug the formulation was preferably taken up by the tumor cells. Thus the two pronged attack on cancerous tissue i.e., inhibition of angiogenesis and killing of cancer cells by anticancer drug, might prove to be a promising approach in the treatment of fatal disease, cancer.

  本研究工作描述了模拟内源性血管生成抑制剂内皮抑素表面结构的精氨酸偶联3.0G聚(丙烯)亚胺(PPI)树枝状大分子的制备，用于肿瘤特异性传递模型抗癌药物盐酸多柔比星(Dox)。通过FTIR、NMR、TEM和质谱法确认了PPI树枝状大分子的合成以及精氨酸与表面基团的 conjugation。通过平衡透析方法加载药物，并评估所开发的制剂的包封效率、溶血毒性、体外药物释放、稳定性、通过体内鸡胚绒毛尿囊膜(CAM)试验评估的抗血管生成活性，以及使用MCF-7癌细胞系进行的抗癌活性和细胞摄取。该系统表现出初始的快速释放随后持续释放Dox，并在CAM试验中显示出显著的抗血管生成活性。此外，精氨酸偶联的树枝状大分子在体内研究中被发现能抑制MCF-7细胞系的癌细胞生长。细胞摄取研究表明，与自由药物相比，制剂更优先被肿瘤细胞摄取。因此，针对癌细胞组织的两种攻击方式，即抑制血管生成和通过抗癌药物杀灭癌细胞，可能成为治疗致命疾病癌症的有前景的方法。
• Anionic sulfonated and carboxylated PPI dendrimers with the EDA core: synthesis and characterization of selective metal complexing agents
  作者：Sandra García-Gallego、Michela Cangiotti、Luigi Fiorani、Alberto Fattori、Ma Ángeles Muñoz-Fernández、Rafael Gomez、M. Francesca Ottaviani、F. Javier de la Mata

  DOI：10.1039/c3dt32870h

  日期：——

  Herein we describe the synthesis and characterization of new sulfonated and carboxylated poly(propyleneimino) (PPI) dendrimers with the ethylenediamino (EDA) core, at generations 1, 2 and 3. By means of UV-Vis and EPR spectroscopy, using Cu2+ as a probe, we concluded that these dendrimers show a specific pattern in the coordination of metal ions. In agreement with the UV-Vis studies, EPR spectra of carboxylated compounds are constituted by 3 different signals which appear and then disappear with increasing copper concentration, corresponding to the saturation of different copper complexation sites. At the lowest copper concentration up to a 1 : 1 molar ratio between CuII and the dendrimer, the spectrum is characteristic of a CuN2O2 coordination at the core of the dendrimer. The spectrum appearing at higher CuII concentrations indicates a peripheral location of the ions coordinating one nitrogen and 3 oxygen atoms in a square planar geometry in restricted mobility conditions. For the highest concentrations tested, copper ions are confined at the external dendrimer surface with CuO4 coordination. For sulfonate systems, the EPR results are in line with a weaker interaction of CuII with the nitrogen sites and a stronger interaction with the oxygen (SO3−) groups with respect to the interactions measured by EPR for carboxylate systems.

  本文中，我们描述了具有乙二胺（EDA）核心的新型磺酸化和羧酸化的聚（丙烯亚胺）（PPI）树枝状大分子的合成与表征，涉及1代、2代和3代。通过使用Cu$^2+}$作为探针的UV-Vis和EPR光谱学手段，我们得出结论，这些树枝状大分子在金属离子的配位上显示出特定的模式。与UV-Vis研究一致，羧酸化化合物的EPR光谱由3种不同信号组成，这些信号随着铜浓度的增加出现并随后消失，对应于不同铜配位位点的饱和。在铜浓度最低至1:1的Cu$^2+}$与树枝状大分子摩尔比时，光谱特征为树枝状大分子核心的CuN2O2配位。在较高Cu$^2+}$浓度下出现的光谱表明，离子在外周位置配位，以四边形平面几何结构在一个氮和三个氧原子进行配位，处于受限运动条件。对于所测试的最高浓度，铜离子被限制在树枝状大分子的外表面，具有CuO4配位。对于磺酸盐系统，EPR结果表明，与氮位点的Cu$^2+}$相互作用较弱，与氧（SO3$^-$）位点的相互作用较强，相较于通过EPR测量的羧酸盐系统的相互作用。
• Lipophilic urea-functionalized dendrimers as efficient carriers for oxyanions†‡
  作者：Holger Stephan、Hartmut Spies、Bernd Johannsen、Lars Klein、Fritz Vögtle

  DOI：10.1039/a905862a

  日期：——

  Urea-functionalized dendrimers are prepared which show very efficient phase transfer, in particular of the diagnostically relevant anions pertechnetate, perrhenate and ATP; the extractability rates are evaluated quantitatively by tracer methods; their pH dependancy allows controlled release of guest molecules from the dendrimer host.

  制备了尿素功能化树枝状聚合物，显示出非常高效的相转移，特别是对诊断相关的阴离子如钽酸根、铼酸根和ATP的转移；其提取率通过示踪法进行了定量评估；它们的pH依赖性允许控制从树枝状聚合物宿主中释放客分子。
• Selective Activation, Different Branching and Grafting of Poly(propylenimine)-Dendrimers
  作者：Andreas Archut、Sven Gestermann、Richard Hesse、Christopher Kauffmann、Fritz Vögtle

  DOI：10.1055/s-1998-1691

  日期：1998.5

  Each branch of different generations of poly(propylenimine)-dendrimers is selectively bifunctionalized by easily accessible reagents. Sulfonic acid chlorides react readily with terminal primary amino groups of this dendrimer type in high yields. The sulfonamide dendrimers purely obtained in this way reveal a considerable synthetic potential. The substitution of the sulfonamide proton of each branch by means of alkyl and benzyl halides, respectively, can be used for a second multiple functionalization. Other convergently synthesized dendrons are grafted on by alkylation of such oligo sulfonamide dendrimers using dendritic halides resulting in structure perfect difunctionalized dendrimers.

  不同代的聚（丙烯酰胺）树枝状聚合物的每个分支通过易于获取的试剂选择性双功能化。磺酸氯化物与这种类型的树枝状聚合物的末端初级氨基群反应迅速，产率高。通过这种方式纯粹获得的磺amide 树枝状聚合物显示出相当大的合成潜力。可以通过相应的烷基和苄基卤化物取代每个分支的磺amide 质子，从而实现第二次多重功能化。其他共聚合合成的树枝状单体通过使用树枝状卤化物对这种低聚磺amide 树枝状聚合物进行烷基化，从而接枝，最终形成结构完美的双功能化树枝状聚合物。
• Photochemical and photophysical properties of a poly(propylene amine) dendrimer functionalised with E-stilbene units
  作者：Veronica Vicinelli、Paola Ceroni、Mauro Maestri、Mariachiara Lazzari、Vincenzo Balzani、Sang-Kyu Lee、Jeroen van Heyst、Fritz Vögtle

  DOI：10.1039/b404463k

  日期：——

  A second generation poly(propylene amine) dendrimer (2) functionalised at the periphery with eight E-stilbene and eight 4-tert-butylbenzenesulfonyl units has been prepared. The absorption spectrum, fluorescence spectrum and decay, E ⇆ Z photoisomerization, and photocyclization of the Z-isomer of the stilbene units have been investigated in air equilibrated acetonitrile solutions. For comparison purposes, a reference compound of the peripheral dendrimer units, namely 4-tert-butyl-N-propyl-N-(4-styryl-benzyl)-benzenesulfonamide (1), has also been studied. The quantum yield of the E→Z photoisomerization reaction (0.30) and the fluorescence quantum yield of the E isomer (0.014) are substantially smaller for the units appended to the dendrimer compared to those of the reference compound 1 (0.50 and 0.046, respectively). The presence of a red tail and the biexponential decay of the emission band of the dendrimer indicate formation of excimers between the stilbene units appended at the poly(propylene amine) dendritic structure. Under the experimental conditions used (λexc = 313 nm), a Z/E photostationary state (around 9 ∶ 1 for both reference compound 1 and dendrimer 2) is reached in the time scale of minutes. On continuing irradiation, other photoreactions take place in the time scale of hours: the stilbene moiety of compound 1 undergoes photocyclization to phenanthrene (quantum yield 0.015), whereas in dendrimer 2 photocyclization to phenanthrene is accompanied by other processes, including a photoreaction involving the internal amine groups.

  已合成一种第二代聚（丙烯胺）树状聚合物（2），其外围功能化有八个E-苯乙烯和八个4-叔丁基苯磺酰基单位。已在空气平衡的乙腈溶液中研究了其吸收光谱、荧光光谱及衰减情况、E⇆Z光异构化以及Z-异构体的光环化。为比较 purposes，作为外围树状聚合物单位的参考化合物，即4-叔丁基-N-丙基-N-(4-苯乙烯基-苄基)-苯磺酰胺（1），也进行了研究。与参考化合物1（分别为0.50和0.046）相比，树状聚合物上附加单位的E→Z光异构化反应的量子产率（0.30）和E异构体的荧光量子产率（0.014）显著较小。树状聚合物发射带的红尾和双指数衰减表明在聚（丙烯胺）树状结构中附加的苯乙烯单位之间形成了激基体。在所用的实验条件下（λexc = 313 nm），达到一个Z/E光静态状态（参考化合物1和树状聚合物2均约为9∶1），时间尺度为几分钟。在持续照射的情况下，其他光反应发生在小时级别的时间尺度内：化合物1的苯乙烯基团经历光环化生成菲（量子产率为0.015），而在树状聚合物2中，光环化生成菲伴随着其他过程，包括涉及内胺基团的光反应。