1,1′-(5-{2-[2-(2-aminoethoxy)ethoxy]ethoxy}-1,3-phenylene)bis[N,N-bis(pyridin-2-ylmethyl)methanamine] | 852486-81-8

• 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: 1,1′-(5-{2-[2-(2-aminoethoxy)ethoxy]ethoxy}-1,3-phenylene)bis[N,N-bis(pyridin-2-ylmethyl)methanamine]
• 英文别名: 1,1'-(5-{2-[2-(2-aminoethoxy)ethoxy]ethoxy}-1,3-phenylene)bis[N,N-bis(pyridin-2-ylmethyl)methanamine]；2-[2-[2-[3,5-bis[[bis(pyridin-2-ylmethyl)amino]methyl]phenoxy]ethoxy]ethoxy]ethanamine
• CAS: 852486-81-8
• 化学式: C₃₈H₄₅N₇O₃
• 分子量: 647.82
• InChiKey: DXMWSOVSPRJJAG-UHFFFAOYSA-N

物化性质

• 沸点：
  746.4±60.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  48
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  丹酰氯 、 1,1′-(5-{2-[2-(2-aminoethoxy)ethoxy]ethoxy}-1,3-phenylene)bis[N,N-bis(pyridin-2-ylmethyl)methanamine] 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以68%的产率得到N-[2-[2-[2-[3,5-bis[[bis(pyridin-2-ylmethyl)amino]methyl]phenoxy]ethoxy]ethoxy]ethyl]-5-(dimethylamino)naphthalene-1-sulfonamide
  参考文献：
  名称：

  Selective recognition of bacterial membranes by zinc(ii)-coordination complexes

  摘要：

  通过荧光显微镜观察到，两个荧光染料–二吡啶基氨基–锌离子结合物 preferentially 染色细菌细胞膜，而对哺乳动物细胞的染色效果较弱。

  DOI：

  10.1039/b517519d
• 作为产物：
  描述：

  5-羟基间苯二甲酸 在 lithium aluminium tetrahydride 、 四溴化碳 、 硫酸 、 potassium carbonate 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 26.0h， 生成 1,1′-(5-{2-[2-(2-aminoethoxy)ethoxy]ethoxy}-1,3-phenylene)bis[N,N-bis(pyridin-2-ylmethyl)methanamine]
  参考文献：
  名称：

  Fluorophore-linked zinc(II)dipicolylamine coordination complexes as sensors for phosphatidylserine-containing membranes

  摘要：

  A series of Zn2+-2,2'-dipicolylamine (Zn2+-DPA) coordination complexes with an attached NBD fluorophore are synthesized and evaluated as fluorescent sensors. The sensors do not respond to vesicles composed of zwitterionic phosphatidylcholine, but the NBD fluorescence emission is enhanced in the presence of anionic vesicles. A sensor with two Zn2+-DPA units and a hydrophilic tris(ethyleneoxy) linker produced a larger emission enhancement than an analogue with a butyl linker, and titration with 1:1 POPC:POPS vesicles lead to an apparent phospholipid association constant of 5.3 x 104 M-1. The sensor can detect the presence of vesicles containing as little as 5% phosphatidylserine. The sensing effect apparently requires a membrane surface because the sensors do not respond to a phosphatidylserine derivative that is monodispersed in aqueous solution. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.08.052

文献信息

• Development of radiolabeled bis(zinc(II)-dipicolylamine) complexes for cell death imaging
  作者：Miho Aoki、Akira Odani、Kazuma Ogawa

  DOI：10.1007/s12149-019-01339-8

  日期：2019.5

  Although it has been traditionally surmised that phosphatidylserine (PS) externalization is a hallmark of apoptosis, most other non-apoptotic modes of cell death, such as necrosis, are also associated with PS externalization. Bis(zinc-dipicolylamine) (ZnDPA) complexes have been reported to exhibit affinity for PS. The present study aimed to develop novel radiolabeled ZnDPA derivatives for cell death imaging in tumor after treatment with anticancer drugs. [125I]IB-EG2-ZnDPA and [99mTc]Tc-MAG3-EG2-ZnDPA were designed and prepared. The stabilities of these radiotracers were determined in 0.1 M phosphate buffer (pH 7.4) or murine plasma at 37 °C, and their 1-octanol/water partition coefficients (logP) were measured. The uptake of radioactivity in cancer cells, which were preincubated in a normal medium or in a medium containing 5-FU, was measured after incubation with radiotracers. Accumulation of [99mTc]Tc-MAG3-EG2-ZnDPA in the tumor was evaluated in tumor-bearing mice treated with or without 5-FU, and then TUNEL staining was performed to detect dead cells in the tumor tissue sections. The radiochemical purities of [125I]IB-EG2-ZnDPA and [99mTc]Tc-MAG3-EG2-ZnDPA exceeded 95%. Although [125I]IB-EG2-ZnDPA gradually decomposing with time, more than 90% of [99mTc]Tc-MAG3-EG2-ZnDPA remained in its intact form in phosphate buffer through 6 h of incubation. Neither [125I]IB-EG2-ZnDPA nor [99mTc]Tc-MAG3-EG2-ZnDPA decomposed so much after 6-h incubation in murine plasma. [125I]IB-EG2-ZnDPA could not specifically recognize PS on the cell surface because of its high lipophilicity. Conversely, [99mTc]Tc-MAG3-EG2-ZnDPA accumulated in cancer cells after treatment with an anticancer drug both in vitro and in vivo, and its accumulation was correlated with the number of TUNEL-positive cells. However, the biodistribution of [99mTc]Tc-MAG3-EG2-ZnDPA was not suitable for imaging because of its low accumulation in tumor and high uptake in abdomen organs. [99mTc]Tc-MAG3-EG2-ZnDPA could be useful for the early detection of treatment effects after chemotherapy. Since the signal-to-noise ratio is not enough for single photon emission computed tomography imaging, further modification is needed to improve its biodistribution and affinity for PS.

  尽管传统上认为磷脂酰丝氨酸（PS）外化是细胞凋亡的标志，但大多数其他非凋亡性细胞死亡模式（如坏死）也与 PS 外化有关。据报道，双（锌-二羟基胺）（ZnDPA）复合物对 PS 具有亲和力。本研究旨在开发新型放射性标记 ZnDPA 衍生物，用于抗癌药物治疗后的肿瘤细胞死亡成像。研究人员设计并制备了[125I]IB-EG2-ZnDPA 和[99mTc]Tc-MAG3-EG2-ZnDPA。在 0.1 M 磷酸盐缓冲液（pH 7.4）或小鼠血浆（37 ℃）中测定了这些放射性racer的稳定性，并测量了它们的 1-辛醇/水分配系数（logP）。癌细胞在正常培养基或含有 5-FU 的培养基中预处理后，在与放射性核素孵育后测量了癌细胞对放射性的摄取。在接受或不接受 5-FU 治疗的肿瘤小鼠体内评估[99mTc]Tc-MAG3-EG2-ZnDPA 在肿瘤中的积累情况，然后进行 TUNEL 染色以检测肿瘤组织切片中的死亡细胞。[125I]IB-EG2-ZnDPA和[99mTc]Tc-MAG3-EG2-ZnDPA的放射化学纯度均超过95%。虽然[125I]IB-EG2-ZnDPA 会随着时间的推移而逐渐分解，但在磷酸盐缓冲液中培养 6 h 后，90% 以上的[99mTc]Tc-MAG3-EG2-ZnDPA 仍保持完整形态。[125I]IB-EG2-ZnDPA和[99mTc]Tc-MAG3-EG2-ZnDPA在小鼠血浆中培养6小时后的分解程度都不高。由于[125I]IB-EG2-ZnDPA具有很高的亲脂性，因此它不能特异性地识别细胞表面的 PS。相反，[99mTc]Tc-MAG3-EG2-ZnDPA 在体外和体内经抗癌药物处理后会在癌细胞中积累，其积累与 TUNEL 阳性细胞的数量相关。然而，[99m锝]Tc-MAG3-EG2-ZnDPA 的生物分布不适合成像，因为它在肿瘤中的蓄积量低，而在腹部器官中的摄取量高。[99m锝]Tc-MAG3-EG2-ZnDPA可用于化疗后治疗效果的早期检测。由于其信噪比不足以用于单光子发射计算机断层扫描成像，因此需要进一步改进其生物分布和对 PS 的亲和性。
• PROBES FOR ANIONIC CELL SURFACE DETECTION
  申请人：Smith Bradley D.

  公开号：US20080171351A1

  公开（公告）日：2008-07-17

  Embodiments of the present invention are generally directed to compositions comprising a class of molecular probes for detecting the presence of anionic cell surfaces. Embodiments include compositions that are enriched for these compositions and preparations, particularly preparations suitable for use as laboratory/clinical reagents and diagnostic indicators, either alone or as part of a kit. An embodiment of the invention provides for a highly selective agent useful in the discernment and identification of dead or dying cells, such as apoptotic cells, in a relatively calcium-free environment. An embodiment of the invention provides a selective agent for the identification of bacteria in a mixed population of bacterial cells and nonbacterial cells.
• US8389223B2
  申请人：——

  公开号：US8389223B2

  公开（公告）日：2013-03-05
• Selective recognition of bacterial membranes by zinc(ii)-coordination complexes
  作者：W. Matthew Leevy、James R. Johnson、C. Lakshmi、Joshua Morris、Manuel Marquez、Bradley D. Smith

  DOI：10.1039/b517519d

  日期：——

  Two fluorophore–dipicolylamine–Zn2+ conjugates are shown by epifluorescence microscopy to stain the membranes of bacterial cells in preference to mammalian cells.

  通过荧光显微镜观察到，两个荧光染料–二吡啶基氨基–锌离子结合物 preferentially 染色细菌细胞膜，而对哺乳动物细胞的染色效果较弱。
• Fluorophore-linked zinc(II)dipicolylamine coordination complexes as sensors for phosphatidylserine-containing membranes
  作者：C. Lakshmi、Roger G. Hanshaw、Bradley D. Smith

  DOI：10.1016/j.tet.2004.08.052

  日期：2004.11

  A series of Zn2+-2,2'-dipicolylamine (Zn2+-DPA) coordination complexes with an attached NBD fluorophore are synthesized and evaluated as fluorescent sensors. The sensors do not respond to vesicles composed of zwitterionic phosphatidylcholine, but the NBD fluorescence emission is enhanced in the presence of anionic vesicles. A sensor with two Zn2+-DPA units and a hydrophilic tris(ethyleneoxy) linker produced a larger emission enhancement than an analogue with a butyl linker, and titration with 1:1 POPC:POPS vesicles lead to an apparent phospholipid association constant of 5.3 x 104 M-1. The sensor can detect the presence of vesicles containing as little as 5% phosphatidylserine. The sensing effect apparently requires a membrane surface because the sensors do not respond to a phosphatidylserine derivative that is monodispersed in aqueous solution. (C) 2004 Elsevier Ltd. All rights reserved.