tripropargyl cryptophane-A | 947590-85-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: tripropargyl cryptophane-A
• 英文别名: 7,35,42-Trimethoxy-14,21,28-tris(prop-2-ynoxy)-9,12,30,33,43,46-hexaoxadecacyclo[20.20.4.38,37.316,29.113,17.134,38.03,40.019,24.05,49.026,52]tetrapentaconta-1(42),2,5,7,13,15,17(54),19,21,23,26,28,34,36,38(47),40,49,51-octadecaene
• CAS: 947590-85-4
• 化学式: C₆₀H₅₄O₁₂
• 分子量: 967.082
• InChiKey: GOWVTVOVKLUSQS-UHFFFAOYSA-N

物化性质

• 熔点：
  >200 °C (decomp)
• 密度：
  1.241±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.8
• 重原子数：
  72
• 可旋转键数：
  9
• 环数：
  20.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  3-溴丙酸 、 tripropargyl cryptophane-A 在 2,6-二甲基吡啶 、 copper(II) sulfate sodium azide 、 potassium carbonate 、 sodium ascorbate 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 以92%的产率得到3-[4-[[35,42-Bis[[1-(2-carboxyethyl)triazol-4-yl]methoxy]-14,21,28-trimethoxy-9,12,30,33,43,46-hexaoxadecacyclo[20.20.4.38,37.316,29.113,17.134,38.03,40.019,24.05,49.026,52]tetrapentaconta-1(42),2,5,7,13,15,17(54),19,21,23,26,28,34,36,38(47),40,49,51-octadecaen-7-yl]oxymethyl]triazol-1-yl]propanoic acid
  参考文献：
  名称：

  Thermodynamics of Xenon Binding to Cryptophane in Water and Human Plasma

  摘要：

  Xenon-129 biosensors offer an attractive alternative to conventional MRI contrast agents due to the chemical shift sensitivity and large nuclear magnetic resonance signal of hyperpolarized Xe-129. Here we report the use of fluorescence spectroscopy and isothermal titration calorimetry (ITC) to determine xenon binding affinity and thermodynamics with a water-soluble triacid-cryptophane-A (1). 1 was synthesized in 10 steps with a 4% overall yield. Fluorescence spectroscopy measured an association constant of (1.7 +/- 0.2) x 10(4) M-1 in phosphate buffer at 293 K. ITC measurements at 293 and 310 K yielded association constants of (1.73 +/- 0.17) x 10(4) and (3.01 +/- 0.26) x 10(4) M-1 and indicated a large entropic contribution to xenon binding in water. On the basis of these data, cryptophane 1 showed roughly 2-fold higher affinity for xenon than any previously measured compound. Remarkably, ITC measurements in human plasma at 310 K gave a similar binding constant, K-A = (2.19 +/- 0.22) x 10(4) M-1, which supports the development of Xe-129 NMR biosensors for biological applications.

  DOI：

  10.1021/ja072965p
• 作为产物：
  描述：

  [3-propargyloxy-4-(2-iodoethoxy)phenyl]methanol 在 高氯酸 、 caesium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.5h， 生成 tripropargyl cryptophane-A
  参考文献：
  名称：

  Thermodynamics of Xenon Binding to Cryptophane in Water and Human Plasma

  摘要：

  Xenon-129 biosensors offer an attractive alternative to conventional MRI contrast agents due to the chemical shift sensitivity and large nuclear magnetic resonance signal of hyperpolarized Xe-129. Here we report the use of fluorescence spectroscopy and isothermal titration calorimetry (ITC) to determine xenon binding affinity and thermodynamics with a water-soluble triacid-cryptophane-A (1). 1 was synthesized in 10 steps with a 4% overall yield. Fluorescence spectroscopy measured an association constant of (1.7 +/- 0.2) x 10(4) M-1 in phosphate buffer at 293 K. ITC measurements at 293 and 310 K yielded association constants of (1.73 +/- 0.17) x 10(4) and (3.01 +/- 0.26) x 10(4) M-1 and indicated a large entropic contribution to xenon binding in water. On the basis of these data, cryptophane 1 showed roughly 2-fold higher affinity for xenon than any previously measured compound. Remarkably, ITC measurements in human plasma at 310 K gave a similar binding constant, K-A = (2.19 +/- 0.22) x 10(4) M-1, which supports the development of Xe-129 NMR biosensors for biological applications.

  DOI：

  10.1021/ja072965p

文献信息

• Cryptophane Xenon-129 Nuclear Magnetic Resonance Biosensors Targeting Human Carbonic Anhydrase
  作者：Jennifer M. Chambers、P. Aru Hill、Julie A. Aaron、Zhaohui Han、David W. Christianson、Nicholas N. Kuzma、Ivan J. Dmochowski

  DOI：10.1021/ja806092w

  日期：2009.1.21

  eight-bond-linked biosensor containing a single xenon atom in the CAII active site. Biosensor dissociation constants (K(d) = 20-110 nM) were determined by isothermal titration calorimetry (ITC) for isozymes CA I and II. The biosensor-CA complexes yielded "bound" hyperpolarized (129)Xe NMR resonances of narrow line width that were shifted by 3.0-7.5 ppm downfield, signifying much larger shifts than seen previously

  (129)Xe NMR 生物传感器是用于早期疾病检测的有前景的试剂，特别是当它们与目标生物分子的相互作用可以扰乱 (129)Xe 化学位移，远远超出临床 MRI 的典型场不均匀性时。我们引入人碳酸酐酶（CA）作为单结合位点酶来研究氙生物传感器-蛋白质相互作用。用不同长度的对苯磺酰胺连接体取代与氙结合的密码烷，产生具有单一 (129)Xe NMR 共振的非非对映生物传感器。 X 射线晶体学证实了 CAII 活性位点上含有单个氙原子的八键连接生物传感器的结合。通过等温滴定量热法 (ITC) 测定同工酶 CA I 和 II 的生物传感器解离常数 (K(d) = 20-110 nM)。生物传感器-CA复合物产生了窄线宽的“结合”超极化(129)Xe NMR共振，其向低场偏移了3.0-7.5 ppm，这意味着比之前看到的偏移大得多。此外，尽管 CA I 和 II 的结构相似，但同工酶特异性化学位移明
• Monomeric Cryptophane with Record-High Xe Affinity Gives Insights into Aggregation-Dependent Sensing
  作者：Serge D. Zemerov、Yannan Lin、Ivan J. Dmochowski

  DOI：10.1021/acs.analchem.0c03776

  日期：2021.1.26

  Cryptophane host molecules provide ultrasensitive contrast agents for 129Xe NMR/MRI. To investigate key features of cryptophane–Xe sensing behavior, we designed a novel water-soluble cryptophane with a pendant hydrophobic adamantyl moiety, which has good affinity for a model receptor, beta-cyclodextrin (β-CD). Adamantyl-functionalized cryptophane-A (AFCA) was synthesized and characterized for Xe affinity

  Cryptophane 主体分子为129 Xe NMR/MRI提供超灵敏的造影剂。为了研究cryptophane-Xe传感行为的关键特征，我们设计了一种新型水溶性cryptophane，它带有一个疏水性金刚烷基侧基，对模型受体β-环糊精（β-CD）具有良好的亲和力。合成了金刚烷基功能化的cryptophane-A (AFCA)，并在不同的AFCA 和β-CD 浓度下对Xe 亲和力、129 Xe NMR 信号和聚集状态进行了表征。Xe-AFCA 缔合常数通过荧光猝灭测定，K A = 114,000 ± 5000 M –1在 293 K，这是报道的对磷酸盐缓冲盐水 (pH 7.2) 中的cryptophane 宿主的最高亲和力。无超极化 (hp)与 AFCA 结合的 Xe 对应的129 Xe NMR 峰在高 (100 μM) AFCA 浓度下直接观察到，其中观察到小的cryptophane 聚集体，并且仅在低
• Synthesis of Enantiopure, Trisubstituted Cryptophane-A Derivatives
  作者：Olena Taratula、Michael P. Kim、Yubin Bai、John P. Philbin、Brittany A. Riggle、Danniebelle N. Haase、Ivan J. Dmochowski

  DOI：10.1021/ol300943w

  日期：2012.7.20

  The efficient synthesis of enantiopure, trisubstituted cryptophane-A derivatives, organic host molecules with unusually high xenon affinity, is reported. Synthesis and chromatographic separation of (±) tri-Mosher’s acid substituted cryptophane diastereomers gave ready access to the enantiopure cryptophanes, which are critical components in the design of enantiomerically pure 129Xe biosensors. Hyperpolarized

  报告了对映体纯、三取代的cryptophane-A 衍生物、具有异常高氙亲和力的有机宿主分子的有效合成。(±) tri-Mosher 酸取代的隐甲非对映异构体的合成和色谱分离可以方便地获得对映纯的隐甲，这是设计对映纯129 Xe 生物传感器的关键组成部分。超极化129 Xe NMR 光谱确定了两个三取代隐甲非对映异构体的单共振，它们之间的距离为 9.5 ppm。这突出了使用对映纯氙生物传感器在不同生化环境中同时检测129 Xe 的机会。
• Enantiopure cryptophane-¹²⁹Xe nuclear magnetic resonance biosensors targeting carbonic anhydrase
  作者：Olena Taratula、Yubin Bai、Edward L. D'Antonio、Ivan J. Dmochowski

  DOI：10.1080/10610278.2014.906601

  日期：2015.2.1

  The (+) and (-) enantiomers for a cryptophane-7-bond-linker-benzenesulfonamide biosensor (C7B) were synthesised and their chirality was confirmed by electronic circular dichroism spectroscopy. Biosensor binding to carbonic anhydrase II (CAII) was characterised for both enantiomers by hyperpolarised (HP) Xe-129 NMR spectroscopy. Our previous study of the racemic (+/-) C7B biosensor-CAII complex [Chambers, J.M.; Hill, P.A.; Aaron, J.A.; Han, Z.H.; Christianson, D.W.; Kuzma, N.N.; Dmochowski, I.J. J. Am. Chem. Soc.2009, 131, 563-569] identified two 'bound' Xe-129@C7B peaks by HP Xe-129 NMR (at 71 and 67ppm, relative to 'free' biosensor at 64ppm), which led to the initial hypothesis that (+) and (-) enantiomers produce diastereomeric peaks when coordinated to Zn2+ at the chiral CAII active site. Unexpectedly, the single enantiomers complexed with CAII also identified two 'bound' Xe-129@C7B peaks: (+) 72, 68ppm and (-) 68, 67ppm. These results are consistent with X-ray crystallographic evidence for benzenesulfonamide inhibitors occupying a second site near the CAII surface. As illustrated by our studies of this model protein-ligand interaction, HP Xe-129 NMR spectroscopy can be useful for identifying supramolecular assemblies in solution.
• Thermodynamics of Xenon Binding to Cryptophane in Water and Human Plasma
  作者：P. Aru Hill、Qian Wei、Roderic G. Eckenhoff、Ivan J. Dmochowski

  DOI：10.1021/ja072965p

  日期：2007.8.1

  Xenon-129 biosensors offer an attractive alternative to conventional MRI contrast agents due to the chemical shift sensitivity and large nuclear magnetic resonance signal of hyperpolarized Xe-129. Here we report the use of fluorescence spectroscopy and isothermal titration calorimetry (ITC) to determine xenon binding affinity and thermodynamics with a water-soluble triacid-cryptophane-A (1). 1 was synthesized in 10 steps with a 4% overall yield. Fluorescence spectroscopy measured an association constant of (1.7 +/- 0.2) x 10(4) M-1 in phosphate buffer at 293 K. ITC measurements at 293 and 310 K yielded association constants of (1.73 +/- 0.17) x 10(4) and (3.01 +/- 0.26) x 10(4) M-1 and indicated a large entropic contribution to xenon binding in water. On the basis of these data, cryptophane 1 showed roughly 2-fold higher affinity for xenon than any previously measured compound. Remarkably, ITC measurements in human plasma at 310 K gave a similar binding constant, K-A = (2.19 +/- 0.22) x 10(4) M-1, which supports the development of Xe-129 NMR biosensors for biological applications.