N,N'-di-(n-12-bromododecyl)-4,13-diaza-18-crown-6 | 165191-78-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N,N'-di-(n-12-bromododecyl)-4,13-diaza-18-crown-6
• 英文别名: N,N'-bis(12-bromododecyl)diaza-18-crown-6；7,16-Bis(12-bromododecyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane
• CAS: 165191-78-6
• 化学式: C₃₆H₇₂Br₂N₂O₄
• 分子量: 756.787
• InChiKey: HTLXTPSDJYGYFQ-UHFFFAOYSA-N

物化性质

• 沸点：
  725.0±55.0 °C(Predicted)
• 密度：
  1.085±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  44
• 可旋转键数：
  24
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-di-(n-12-bromododecyl)-4,13-diaza-18-crown-6 在 palladium on activated charcoal 氢气 、 sodium carbonate 、 potassium iodide 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、482.63 kPa 条件下， 反应 96.0h， 生成 N,N'-bis[12-(diaza-18-crown-6)dodecyl]-18-crown-6
  参考文献：
  名称：

  Synthetic Models for Transmembrane Channels: Structural Variations That Alter Cation Flux

  摘要：

  Twelve novel bis- or tris(macrocyclic) compounds have been designed as models for cation-conducting channels that function in phospholipid bilayer vesicle membranes. In general, the channel model systems have the structure ''sidearm-crown-spacer-crown-spacer-crown-sidearm'', although certain features have been altered from compound to compound to assess the structure-activity relationship. Two additional compounds have been prepared exclusively as controls. The ionophores have been incorporated into the membranes either by warming the compound with the preformed vesicle or by incorporation during vesicle formation. The two methods gave identical results within experimental error. Cation flux was assessed by two different analytical methods. In one case, the fluorescent dye pyranine was encapsulated within vesicles containing ionophore. Proton transport was then monitored by changes in dye fluorescence with time following an acid pulse. Ionophoretic activity far most of the compounds was studied using a dynamic NMR method in which the flux rate of Na-23(+) through the bilayer was monitored. All NMR studies were done in conjunction with gramicidin as a control to minimize experimental variations from run to run. Several of the synthetic ionophores showed cation conduction of as much as 40% of the activity of gramicidin. Apparently, small structural changes significantly altered flux rates and two known carriers closely related to the channel formers failed to exhibit measurable transport under comparable conditions.

  DOI：

  10.1021/ja00134a011
• 作为产物：
  描述：

  12-溴十二烷酰氯 在 4-二甲氨基吡啶 、 硼烷 、 三乙胺 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 144.0h， 生成 N,N'-di-(n-12-bromododecyl)-4,13-diaza-18-crown-6
  参考文献：
  名称：

  Synthetic Models for Transmembrane Channels: Structural Variations That Alter Cation Flux

  摘要：

  Twelve novel bis- or tris(macrocyclic) compounds have been designed as models for cation-conducting channels that function in phospholipid bilayer vesicle membranes. In general, the channel model systems have the structure ''sidearm-crown-spacer-crown-spacer-crown-sidearm'', although certain features have been altered from compound to compound to assess the structure-activity relationship. Two additional compounds have been prepared exclusively as controls. The ionophores have been incorporated into the membranes either by warming the compound with the preformed vesicle or by incorporation during vesicle formation. The two methods gave identical results within experimental error. Cation flux was assessed by two different analytical methods. In one case, the fluorescent dye pyranine was encapsulated within vesicles containing ionophore. Proton transport was then monitored by changes in dye fluorescence with time following an acid pulse. Ionophoretic activity far most of the compounds was studied using a dynamic NMR method in which the flux rate of Na-23(+) through the bilayer was monitored. All NMR studies were done in conjunction with gramicidin as a control to minimize experimental variations from run to run. Several of the synthetic ionophores showed cation conduction of as much as 40% of the activity of gramicidin. Apparently, small structural changes significantly altered flux rates and two known carriers closely related to the channel formers failed to exhibit measurable transport under comparable conditions.

  DOI：

  10.1021/ja00134a011

文献信息

• A tris(macrocycle) that exhibits H-bond-induced blockage of the cation channel faction in a phospholipid bilayer
  作者：Oscar Murillo、Ernesto Abel、Glenn E. M. Maguire、George W. Gokel

  DOI：10.1039/cc9960002147

  日期：——

  An indole-terminated tris(macrocyclic) compound, designed to be a channel-former, is an effective carrier in bluk membranes but fails to function in a lipid bilayer owing to hydrogen bond formation which blocks the channel.

  一种以吲哚为末端的含三环的大环化合物，设计初衷是作为通道形成剂，能有效地在胞质膜中充当载体，但由于其在脂双层中形成氢键从而堵塞通道，故无法在该环境中发挥功能。
• Structure–activity relationships, kinetics, selectivity, and mechanistic studies of synthetic hydraphile channels in bacterial and mammalian cells
  作者：W. Matthew Leevy、Seth T. Gammon、Tatiana Levchenko、David D. Daranciang、Oscar Murillo、Vladimir Torchilin、David Piwnica-Worms、James E. Huettner、George W. Gokel

  DOI：10.1039/b508157b

  日期：——

  Hydraphile compounds are shown to be cytotoxic to Gram-negative and Gram-positive bacteria, yeast, and mammalian cells. Their cellular toxicity compares favorably with other synthetic ionophores and rivals that potency of natural antibiotics. The effects of structural variations on toxicity are described. The effects of these variations correlate well with previous studies of ion transport in liposomes. Whole cell patch clamping with mammalian cells confirms a channel mechanism in living cells suggesting that this family may comprise novel and flexible pharmacological agents.

  水合化合物对革兰氏阴性和革兰氏阳性细菌、酵母和哺乳动物细胞具有细胞毒性。它们的细胞毒性可与其他合成离子活化剂媲美，并可与天然抗生素的毒性相媲美。本文介绍了结构变化对毒性的影响。这些变化的影响与之前对脂质体中离子转运的研究有很好的相关性。哺乳动物细胞的全细胞膜片钳法证实了活细胞中的通道机制，这表明该系列产品可能包含新型灵活的药剂。
• Planar Bilayer Conductance and Fluorescence Studies Confirm the Function and Location of a Synthetic, Sodium-Ion-Conducting Channel in a Phospholipid Bilayer Membrane
  作者：Ernesto Abel、Glenn E. M. Maguire、Eric S. Meadows、Oscar Murillo、Takashi Jin、George W. Gokel

  DOI：10.1021/ja971098t

  日期：1997.9.1
• Hydraphile Channels:  Structural and Fluorescent Probes of Position and Function in a Phospholipid Bilayer
  作者：Ernesto Abel、Glenn E. M. Maguire、Oscar Murillo、Iwao Suzuki、Stephen L. De Wall、George W. Gokel

  DOI：10.1021/ja9909172

  日期：1999.10.1

  Three novel tris(macrocycle)s having fluorescent residues at their distal termini have been prepared and studied. The compounds are of the form R[N18N]C-12[N18N]C-12[N18N]R in which R is 2-(3-indolyl)ethyl (1), 2-(3-(N-methylindolyl))ethyl (2), and dansyl (3). Compounds 2 and 3 were found to transport Naf at rates similar to those of other tris(macrocyclic)s but 1 was not an ionophore in the bilayer as assessed by Na-23 NMR analysis. The latter failure may be due to a hydrogen-bond blockade leading to a globular conformation adopted by the hydraphile. The fluorescence maximum of 3 was determined in a variety of solvents and in a phospholipid bilayer. The polarity experienced by the dansyl group in the bilayer was intermediate between that observed in methanol and ethanol. Fluorescence depth quenching using doxyl-substituted lipids showed that the dansyl headgroups of 3 were 14 Angstrom from the bilayer's midplane or separated by about 28 Angstrom. Fluorescence energy transfer between 2 acid 3 showed that these two hydraphiles were not appreciably aggregated in the bilayer.
• Synthetic Transmembrane Channels:  Functional Characterization Using Solubility Calculations, Transport Studies, and Substituent Effects
  作者：Oscar Murillo、Iwao Suzuki、Ernesto Abel、Clare L. Murray、Eric S. Meadows、Takashi Jin、George W. Gokel

  DOI：10.1021/ja962694a

  日期：1997.6.1

  Dibenzyldiaza-18-crown-6 (PhCH2[N18N]CH2Ph, 1), di(dodecyldiaza-18-crown-6 (C12H25[N18N]C12H25, 2), HOOC(CH2)(11)[N18N](CH2)(11)COOH (3), (18N)(CH2)(12)[N18N](CH2)(12)[N18] (4), [N18N](CH2)(12)[N18N](CH2)(12)[N18N] (5), C12H25[N18N](CH2)(12)[N18N](CH2)(12)[N18N]C12H25 (6), PhCH2[N18N](CH2)(12)[N18N](CH2)(12)[N18N]CH2Ph (7), 4-(p-MeOC6H4CH2[N18N]C-12)(2)[N18N] (8), (p-NO2C6H4CH2[N18N]C-12)(2)[N18N] (9), and [chol-O-(CH2)(2)[N18N]C-12](2)[N18N] (10) were studied. Octanol-water partition coefficients were determined for 1, 6, 7, 8, 10, and 3-cholestanyl-OCOCH2[N18N](CH2)(12)[N18N](CH2)(12)[N18N]COCH2O-3-cholestanyl (11). All were found to favor octanol, and by implication the phospholipid bilayer membrane, by at least 10(4)-fold. Transport of Na+ was assessed in both a phospholipid bilayer and in a bulk CHCl3 membrane phase. Addition of ionophores to the latter was found in some cases to strongly enhance CHCl3 phase hydration. An attempt to correlate transport rates determined in the two systems failed, suggesting that the carrier mechanism, required in the CHCl3 phase, does not apply to the tris(macrocyclic) compounds in the bilayer. Sodium transport rates were also assessed for these compounds by using the bilayer clamp technique. Although Na+ flux rates thus determined for 7-9 in the phospholipid bilayer did not correlate with results obtained by the Na-23-NMR technique, the traces are similar to those obtained with protein channels, further supporting the function of tris(macrocycle)s as channel formers.