N,N'-(4,6-diethynyl-1,3-phenylene)bis(2,2-dimethylpropanamide) | 1346686-34-7

• 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: N,N'-(4,6-diethynyl-1,3-phenylene)bis(2,2-dimethylpropanamide)
• 英文别名: N-[5-(2,2-dimethylpropanoylamino)-2,4-diethynylphenyl]-2,2-dimethylpropanamide
• CAS: 1346686-34-7
• 化学式: C₂₀H₂₄N₂O₂
• 分子量: 324.423
• InChiKey: FHGJIUHGWPLOGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N,N'-(4,6-diethynyl-1,3-phenylene)bis(2,2-dimethylpropanamide) 、 N-(1-hexylheptyl)-3-azido-1,8-naphthalimide 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 12.0h， 以40%的产率得到N-[2,4-bis[1-(1,3-dioxo-2-tridecan-7-ylbenzo[de]isoquinolin-5-yl)triazol-4-yl]-5-[(1-hydroxy-2,2-dimethylpropylidene)amino]phenyl]-2,2-dimethylpropanimidic acid
  参考文献：
  名称：

  Polarized Naphthalimide CH Donors Enhance Cl^– Binding within an Aryl-Triazole Receptor

  摘要：

  The dipolar character of 1,8-naphthalimide together with polarization of the C-4-H and C-5-H donors has been utilized in receptor 1 to effectively bind chloride alongside triazole and phenylene units. The Cl- binding strength of 1 shows that the naphthalimide provides greater anion stabilization than an unactivated phenylene, and DFT calculations show that its collinear donor array can be a "urea-like" analog for CH center dot center dot center dot anion interactions.

  DOI：

  10.1021/ol202729z
• 作为产物：
  描述：

  N,N'-(1,3-phenylene)bis(2,2-dimethylpropanamide) 在 甲醇 、 copper(l) iodide 、 trans-bis(triphenylphosphine)palladium dichloride 、 一氯化碘 、 potassium carbonate 、 二异丙胺 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 27.25h， 生成 N,N'-(4,6-diethynyl-1,3-phenylene)bis(2,2-dimethylpropanamide)
  参考文献：
  名称：

  Polarized Naphthalimide CH Donors Enhance Cl^– Binding within an Aryl-Triazole Receptor

  摘要：

  The dipolar character of 1,8-naphthalimide together with polarization of the C-4-H and C-5-H donors has been utilized in receptor 1 to effectively bind chloride alongside triazole and phenylene units. The Cl- binding strength of 1 shows that the naphthalimide provides greater anion stabilization than an unactivated phenylene, and DFT calculations show that its collinear donor array can be a "urea-like" analog for CH center dot center dot center dot anion interactions.

  DOI：

  10.1021/ol202729z

文献信息

• Sequence-Controlled Stimuli-Responsive Single–Double Helix Conversion between 1:1 and 2:2 Chloride-Foldamer Complexes
  作者：Yun Liu、Fred C. Parks、Wei Zhao、Amar H. Flood

  DOI：10.1021/jacs.8b09899

  日期：2018.11.14

  folded secondary structures, to modulate their stabilities, and to control the resultant functions. Our ability to encode such information into nonbiological oligomers and polymers, however, is still limited. Here, we describe a C2-symmetric aryl-triazole foldamer that assembles into a chloride-templated 2:2 double helix, and the discovery that its interconversion with the simpler 1:1 single helix can

  生物聚合物中的一级序列携带信息以指导折叠二级结构、调节其稳定性并控制由此产生的功能。然而，我们将这些信息编码成非生物低聚物和聚合物的能力仍然有限。在这里，我们描述了一个 C2 对称的芳基三唑折叠体，它组装成一个氯化物模板化的 2:2 双螺旋，并且发现它与更简单的 1:1 单螺旋的相互转化可以由溶剂质量、温度和浓度驱动. 我们在 13 个残基序列（两个末端位点和一个中心位点）中使用单位点替换来揭示双螺旋的稳定性在很大程度上取决于单螺旋和双螺旋之间阴离子结合力的差异以及修饰残基的位置。具体来说，发现以双酰胺亚苯基残基形式在链端放置稳定的 CH…Cl-氢键相互作用非常有利于双螺旋。虽然 π 表面的掩埋和疏溶剂效应也有助于稳定双螺旋，但发现它们的作用对所考虑的修饰不太敏感。这种对化学信息如何被编入一级序列的理解为控制非生物折叠体的结构和特性提供了强大的工具。
• Polarity-Tolerant Chloride Binding in Foldamer Capsules by Programmed Solvent-Exclusion
  作者：Yun Liu、Fred C. Parks、Edward G. Sheetz、Chun-Hsing Chen、Amar H. Flood

  DOI：10.1021/jacs.0c12562

  日期：2021.3.3

  geometry and its ability to exclude solvent were supported by solid-state and solution phase studies. This capsule then withstood a 4-fold increase in solvent dielectric constant (εr) from dichloromethane (9) to acetonitrile (36) while maintaining a high and solvent-independent affinity of 105 M–1; ΔG ∼ 28 kJ mol–1. This behavior is unusual. More typical of solvent-dependent behavior, Cl– affinities

  在广泛的溶液环境中持久的阴离子结合是一项关键挑战，继续激发并要求合成受体设计中的新策略。尽管在低极性溶剂中的牢固结合已成为常规做法，但我们在高极性溶剂中保持高亲和力的能力尚未达到自然设定的标准。阴离子在水性环境中被蛋白质结合并定期运输，该蛋白质使用二级和三级结构从水中分离出阴离子结合位点。受溶剂排斥原理的启发，我们创建了一个序列定义的foldameric胶囊，该胶囊的整体最小构象显示螺旋折叠状态，并预先进行1：1阴离子络合。固态和溶液相研究支持了折叠后的几何形状的高稳定性及其排除溶剂的能力。r）从二氯甲烷（9）到乙腈（36），同时保持10 5 M –1的高且不依赖溶剂的亲和力；Δ ģ〜28千焦耳摩尔-1。这种现象是不寻常的。更典型的依赖性溶剂行为，氯-亲和力见于对照化合物，如芳基-三唑的大环和五元组直线下降，与易受电介质筛选其暴露于溶剂的结合腔。最后，二甲亚砜通过假定的溶剂结合使折叠剂变性，然后降低折叠剂的Cl
• Hydrophobic Collapse of Foldamer Capsules Drives Picomolar-Level Chloride Binding in Aqueous Acetonitrile Solutions
  作者：Yuran Hua、Yun Liu、Chun-Hsing Chen、Amar H. Flood

  DOI：10.1021/ja4074744

  日期：2013.9.25

  Aqueous media are competitive environments in which to perform host-guest chemistry, particularly when the guest is highly charged. While hydrophobic binding is a recognized approach to this challenge in which apolar pockets can be designed to recognize apolar guests in water, complementary strategies are required for hydrophilic anions like chloride. Here, we present evidence of such an alternative

  水性介质是进行主客体化学反应的竞争环境，特别是当客体电荷很高时。虽然疏水结合是应对这一挑战的公认方法，其中可以设计非极性口袋来识别水中的非极性客体，但亲水性阴离子（如氯）需要补充策略。在这里，我们展示了这种替代机制的证据，蛋白质每天都在使用，但人工受体很少使用，其中疏水相互作用被证明负责组织和稳定芳基三唑折叠体，以帮助从越来越多的水溶液中提取亲水性氯离子。其中，双螺旋复合物在掩埋约 80% 的 π 表面后获得稳定性，同时为氢键创造了一个有效的、不含溶剂的微环境。氯化物对双链体的总体亲和力在乙腈中 25% 的水 v/v 中是显着的 (log β2 = 12.6)，并且随着水含量增加到 50%，它仍然很强 (log β2 = 13.0)。随着非生物折叠体的可预测设计的增加，这种水辅助策略原则上可用于结合其他亲水性客体。
• Electrostatic and Allosteric Cooperativity in Ion-Pair Binding: A Quantitative and Coupled Experiment–Theory Study with Aryl–Triazole–Ether Macrocycles
  作者：Bo Qiao、Arkajyoti Sengupta、Yun Liu、Kevin P. McDonald、Maren Pink、Joseph R. Anderson、Krishnan Raghavachari、Amar H. Flood

  DOI：10.1021/jacs.5b05839

  日期：2015.8.5

  Cooperative binding of ion pairs to receptors is crucial for the manipulation of salts, but a comprehensive understanding of cooperativity has been elusive. To this end, we combine experiment and theory to quantify ion-pair binding and to separate allostery from electrostatics to understand their relative contributions. We designed aryl-triazole-ether macrocycles (MC) to be semiflexible, which allows ion pairs (NaX; X = anion) to make contact, and to be monocyclic to simplify analyses. A multiequilibrium model allows us to quantify, for the first time, the experimental cooperativity, alpha, for the equilibrium MC center dot Na+ + MC center dot X- (sic) MC center dot NaX + MC, which is associated with contact ion-pair binding of NaI (alpha = 1300, Delta G(alpha) = -18 kJ mol(-1)) and NaClO4 (alpha = 400, Delta G(alpha) = -15 kJ mol(-1)) in 4:1 dichloromethane-acetonitrile. We used accurate energies from density functional theory to deconvolute how the electrostatic effects and the allosteric changes in receptor geometry individually contribute to cooperativity. Computations, using a continuum solvation model (dichloromethane), show that allostery contributes similar to 30% to overall positive cooperativity. The calculated trend of electrostatic cooperativity using pairs of spherical ions (NaCl > NaBr > NaI) correlates to experimental observations (NaI > NaClO4). We show that intrinsic ionic size, which dictates charge separation distance in contact ion pairs, controls electrostatic cooperativity. This finding supports the design principle that semiflexible receptors can facilitate optimal electrostatic cooperativity. While Coulombs law predicts the size-dependent trend, it overestimates electrostatic cooperativity; we suggest that binding of the individual anion and cation to their respective binding sites dilutes their effective charge. This comprehensive understanding is critical for rational designs of ion-pair receptors for the manipulation of salts.
• Preorganized Aryltriazole Foldamers as Effective Transmembrane Transporters for Chloride Anion
  作者：Jie Shang、Wen Si、Wei Zhao、Yanke Che、Jun-Li Hou、Hua Jiang

  DOI：10.1021/ol501772v

  日期：2014.8.1

  Preorganized aryltriazole foldamers 1 and 2 were designed and synthesized. NMR studies and X-ray analysis demonstrate that 1 adopts a crescent conformation driven by a series of continuous hydrogen bonds at the periphery of the foldamer, whereas 2 displays a coil conformation. NMR titrations reveal that the affinities of fully preorganized foldamer 1 for halogen anions are much stronger that those of partially preorganized foldamer 2. Furthermore, it is found that such full preorganization makes 1 an effective transmembrane transporter for the chloride anion across a lipid bilayer.