1,8-(2,6-pyridinedimethylene)-1,4,8,11-tetraazacyclotetradecane

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1,8-(2,6-pyridinedimethylene)-1,4,8,11-tetraazacyclotetradecane
• 英文别名: 1,9,12,18,22-Pentazatricyclo[7.6.6.13,7]docosa-3(22),4,6-triene
• 化学式: C₁₇H₂₉N₅
• 分子量: 303.451
• InChiKey: YWXHXRBRHRJRPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  43.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,8-(2,6-pyridinedimethylene)-1,4,8,11-tetraazacyclotetradecane 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 90.0h， 生成 1,8-(2,6-pyridinedimethylene)-4-benzyl-8-(tert-butylacetato)-1,4,8,11-tetraazacyclotetradecane
  参考文献：
  名称：

  Pycup—A Bifunctional, Cage-like Ligand for ⁶⁴Cu Radiolabeling

  摘要：

  In developing targeted probes for positron emission tomography (PET) based on Cu-64, stable complexation of the radiometal is key, and a flexible handle for bioconjugation is highly advantageous. Here, we present the synthesis and characterization of the chelator pycup and four derivatives. Pycup is a cross-bridged cyclam derivative with a pyridyl donor atom integrated into the cross-bridge resulting in a pentadentate ligand. The pycup platform provides kinetic inertness toward Cu-64 dechelation and offers versatile bioconjugation chemistry. We varied the number and type of additional donor atoms by alkylation of the remaining two secondary amines, providing three model ligands, pycup2A, pycup1A1Bn, and pycup2Bn, in 3-4 synthetic steps from cyclam. All model copper complexes displayed very slow decomplexation in 5 M HCl and 90 degrees C (t(1/2): 1.5 h for pycup1A1Bn, 2.7 h for pycup2A, 20.3 h for pycup2Bn). The single crystal crystal X-ray structure of the [Cu(pycup2Bn)](2+) Complex showed that the copper was coordinated in a trigonal, bipyramidal manner. The corresponding radiochemical complexes were at least 94% stable in rat plasma after 24 h. Biodistribution studies conducted in Balb/c mice at 2 h postinjection of Cu-64 labeled pycup2A revealed low residual activity in kidney, liver, and blood pool with predominantly renal clearance observed. Pycup2A was readily conjugated to a fibrin-targeted peptide and labeled with Cu-64 for successful PET imaging of arterial thrombosis in a rat model, demonstrating the utility of our new chelator in vivo.

  DOI：

  10.1021/mp400686z
• 作为产物：
  描述：

  间二溴苄 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以53%的产率得到1,8-(2,6-pyridinedimethylene)-1,4,8,11-tetraazacyclotetradecane
  参考文献：
  名称：

  A two-step synthesis of new macrobicyclic aza-ligands starting from “trans”dioxocyclam as diprotected macrocycle

  摘要：

  A rapid and convenient synthesis of two small aza-cryptands containing a 1,4,8,11-tetraazacyclotetradecane backbone is reported. This strategy can be applied to the preparation of many other aza-cages by varying the nature of the cross linker. Moreover, the two remaining secondary amine sites may allow the functionalization of these ligands or their grafting on a polymer. (C) 1997 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)00944-1

文献信息

• A Cyclam‐Based Fluorescent Ligand as a Molecular Beacon for Cu ²⁺ and H ₂ S Detection
  作者：Silvia Mirra、Maria Strianese、Claudio Pellecchia

  DOI：10.1002/ejic.201700623

  日期：2017.9.8

  cyclam-based ligand. Fluorescence experiments corroborate this hypothesis. The system resulted selective in the recognition of copper and stable for a week, as assessed via fluorescence spectroscopy. The Cu(II) complex has been isolated and tested as a fluorescent probe for the detection of H2S. NMR and ESI-MS investigation provided evidence that H2S recognition occurs via a copper displacement mechanism, as

  已经设计、合成了五齿笼状环链烷烃基荧光配体，并通过单维和二维核磁共振分析对其进行了表征。为了进一步表征标题配体 ESI-MS，还进行了紫外可见光和荧光实验。已通过多种光谱技术（即 ESI-MS、紫外可见光和荧光）成功地探索了其作为化学传感器检测 Cu2+ 离子的适用性。Job 的绘图实验与 ESI-MS 实验一起表明 Cu2+ 与基于环菌素的配体结合的化学计量比为 1:1。荧光实验证实了这一假设。根据荧光光谱法的评估，该系统对铜的识别具有选择性，并且可以稳定一周。Cu(II) 复合物已被分离出来并作为检测 H2S 的荧光探针进行测试。NMR 和 ESI-MS 研究提供的证据表明 H2S 识别是通过铜置换机制发生的，如文献中报道的不同铜配合物。该系统通过对 HS 的选择性响应起作用，利用初始荧光强度的浓度依赖性“开启”。
• A two-step synthesis of new macrobicyclic aza-ligands starting from “trans”dioxocyclam as diprotected macrocycle
  作者：Franck Denat、Sylvie Lacour、Stéphane Brandès、Roger Guilard

  DOI：10.1016/s0040-4039(97)00944-1

  日期：1997.6

  A rapid and convenient synthesis of two small aza-cryptands containing a 1,4,8,11-tetraazacyclotetradecane backbone is reported. This strategy can be applied to the preparation of many other aza-cages by varying the nature of the cross linker. Moreover, the two remaining secondary amine sites may allow the functionalization of these ligands or their grafting on a polymer. (C) 1997 Published by Elsevier Science Ltd.
• Pycup—A Bifunctional, Cage-like Ligand for ⁶⁴Cu Radiolabeling
  作者：Eszter Boros、Elena Rybak-Akimova、Jason P. Holland、Tyson Rietz、Nicholas Rotile、Francesco Blasi、Helen Day、Reza Latifi、Peter Caravan

  DOI：10.1021/mp400686z

  日期：2014.2.3

  In developing targeted probes for positron emission tomography (PET) based on Cu-64, stable complexation of the radiometal is key, and a flexible handle for bioconjugation is highly advantageous. Here, we present the synthesis and characterization of the chelator pycup and four derivatives. Pycup is a cross-bridged cyclam derivative with a pyridyl donor atom integrated into the cross-bridge resulting in a pentadentate ligand. The pycup platform provides kinetic inertness toward Cu-64 dechelation and offers versatile bioconjugation chemistry. We varied the number and type of additional donor atoms by alkylation of the remaining two secondary amines, providing three model ligands, pycup2A, pycup1A1Bn, and pycup2Bn, in 3-4 synthetic steps from cyclam. All model copper complexes displayed very slow decomplexation in 5 M HCl and 90 degrees C (t(1/2): 1.5 h for pycup1A1Bn, 2.7 h for pycup2A, 20.3 h for pycup2Bn). The single crystal crystal X-ray structure of the [Cu(pycup2Bn)](2+) Complex showed that the copper was coordinated in a trigonal, bipyramidal manner. The corresponding radiochemical complexes were at least 94% stable in rat plasma after 24 h. Biodistribution studies conducted in Balb/c mice at 2 h postinjection of Cu-64 labeled pycup2A revealed low residual activity in kidney, liver, and blood pool with predominantly renal clearance observed. Pycup2A was readily conjugated to a fibrin-targeted peptide and labeled with Cu-64 for successful PET imaging of arterial thrombosis in a rat model, demonstrating the utility of our new chelator in vivo.