N,N'-bis[3-(3-aminopropyl)methylaminonpropyl]-naphthalene-1,4,5,8-tetracarboxylic acid diimide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N,N'-bis[3-(3-aminopropyl)methylaminonpropyl]-naphthalene-1,4,5,8-tetracarboxylic acid diimide
• 英文别名: N,N'-bis[3-(3-aminopropyl)methylaminopropyl]-naphthalene-1,4,5,8-tetracarboxylic acid diimide；N,N-bis[3-(3-aminopropyl)(methyl)aminopropyl]naphthalene-1,4,5,8-tetracarboxylic acid diimide；N,N'-bis[3-(3-aminopropyl)methylaminopropyl]naphthalene-1,4,5,8-tetracarboxylic acid diimide；N,N-bis[3-(3-aminopropyl)methylaminopropyl]naphthalene-1,4,5,8-tetracarboxylic acid diimide；6,13-Bis[3-[3-aminopropyl(methyl)amino]propyl]-6,13-diazatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),2,4(16),8,10-pentaene-5,7,12,14-tetrone
• 化学式: C₂₈H₃₈N₆O₄
• 分子量: 522.648
• InChiKey: WSPIRMMCQWJOJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,N'-bis[3-(3-aminopropyl)methylaminonpropyl]-naphthalene-1,4,5,8-tetracarboxylic acid diimide 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.17h， 生成
  参考文献：
  名称：

  具有增强的稳定二聚体G-四链体能力的环状萘二酰亚胺二聚体

  摘要：

  设计并合成了一种新型的带有变化的接头长度的二聚环萘二酰亚胺衍生物（cNDI-二聚体），以识别二聚体G-四链体结构。所有cNDI-二聚体均表现出较高的识别G-四链体结构的偏好，并且通过将熔融温度提高23°C以上而显着增强了二聚G-四链体结构相对于cNDI单体的热稳定性。 cNDI二聚体稳定二聚体G-四链体的能力。cNDI二聚体还显示出比cNDI单体更强的抑制端粒酶活性和阻止端粒DNA延伸的能力，这显示出更高的抗癌潜力，可用于进一步的治疗应用。

  DOI：

  10.1002/chem.201901468
• 作为产物：
  描述：

  tert-butyl (3-((3-aminopropyl)(methyl)amino)propyl)carbamate 在 三氟乙酸 作用下， 以 甲苯 为溶剂， 生成 N,N'-bis[3-(3-aminopropyl)methylaminonpropyl]-naphthalene-1,4,5,8-tetracarboxylic acid diimide
  参考文献：
  名称：

  具有增强的稳定二聚体G-四链体能力的环状萘二酰亚胺二聚体

  摘要：

  设计并合成了一种新型的带有变化的接头长度的二聚环萘二酰亚胺衍生物（cNDI-二聚体），以识别二聚体G-四链体结构。所有cNDI-二聚体均表现出较高的识别G-四链体结构的偏好，并且通过将熔融温度提高23°C以上而显着增强了二聚G-四链体结构相对于cNDI单体的热稳定性。 cNDI二聚体稳定二聚体G-四链体的能力。cNDI二聚体还显示出比cNDI单体更强的抑制端粒酶活性和阻止端粒DNA延伸的能力，这显示出更高的抗癌潜力，可用于进一步的治疗应用。

  DOI：

  10.1002/chem.201901468

文献信息

• Design of tetraplex specific ligands: cyclic naphthalene diimide
  作者：Yugo Esaki、Md. Monirul Islam、Satoshi Fujii、Shinobu Sato、Shigeori Takenaka

  DOI：10.1039/c4cc01005a

  日期：——

  Cyclic naphthalene diimide 1 bound to hybrid-type tetraplex DNA from 5′-AGGG(TTAGGG)₃-3′ (K = 8.6 × 10⁶ M⁻¹) with 260-fold greater affinity than that when binding to double stranded oligonucleotide consisting of 5′-GGG AGG TTT CGC-3′ and 3′-CCC TCC AAA GCG-5′ (nK = 3.3 × 10⁴ M⁻¹) with 0.5 μM of IC₅₀ for telomerase activity.

  环状萘二酰亚胺1与5'-AGGG(TTAGGG)3'-3'的混合型四链体DNA结合的亲和力比与由5'-GGG AGG TTT CGC-3'和3'-CCC TCC AAA GCG-5'组成的双链寡核苷酸结合时高260倍（K = 8.6 × 10^6 M^-1），并且对端粒酶活性的IC50为0.5μM（nK = 3.3 × 10^4 M^-1）。
• Ferrocenyl naphthalene diimide can bind to DNA·RNA hetero duplex: potential use in an electrochemical detection of mRNA expression
  作者：Shinobu Sato、Satoshi Fujii、Kenichi Yamashita、Makoto Takagi、Hiroki Kondo、Shigeori Takenaka

  DOI：10.1016/s0022-328x(01)00951-2

  日期：2001.12

  The novel ferrocenyl naphthalene diimide derivative I was synthesized by the condensation reaction between ferroceneacetic acid and terminal amino moieties of two imide substituents of naphthalene diimide. Stopped-flow analysis of the ligand I and DNA interaction revealed the following results: (i) the ligand binds to double stranded DNA more strongly than to single stranded DNA; (ii) the ligand does not have a bias against DNA sequence; (iii) the ligand can bind to the DNA-RNA hetero duplex more strongly than to the DNA-DNA duplex. These properties of I make it a suitable ligand for analysis of not only DNA but RNA. In fact, a current due to I was observed at 269 mV in the differential pulse voltammetric analysis of dA(20)-immobilized electrode in an electrolyte containing 1. The current increased markedly upon hybridization with polyU, whereas no current increase was obtained for polyA. Since the DNA-RNA hetero duplex is formed between sample RNA and DNA on the electrode, I may be used for the electrochemical detection of mRNA expression. (C) 2001 Elsevier Science B.V. All rights reserved.
• Linker effect of ferrocenylnaphthalene diimide ligands in the interaction with double stranded DNA
  作者：Shinobu Sato、Shigeori Takenaka

  DOI：10.1016/j.jorganchem.2008.01.011

  日期：2008.4

  Ferrocenylnaphthalene diimide ligands 1-7 were synthesized by joining a piperazino or N-methylamino linker of the naphthalene diimide skeleton with ferrocenecarboxylic, ferroceneacetic, or ferrocenepropionic parts. Their interaction with double stranded DNA (dsDNA) was studied kinetically and electrochemically. Association rate constants of these ligands were found to correlate with their intramolecular stacking ability between the ferrocene and naphthalene diimide planes: ligands which can adopt a stacked conformation in buffer solution were unfavorable in the association with dsDNA, resulting in a smaller association rate constant. Dissociation rate constants of these ligands carrying the bulky piperazino linker were smaller than that of those carrying an N-methylamino one. Binding constants were dictated by the balance of these two factors. These ligands were applied to the electrochemical detection of the amount of dsDNA on the electrode. Ligand 6 having the highest affinity for dsDNA gave rise to the largest current increase upon dsDNA formation in the electrochemical hybridization assay. (C) 2008 Elsevier B.V. All rights reserved.
• Discrimination of phosphorylated double stranded DNA by naphthalene diimide having zinc(II) dipicolylamine complexes
  作者：Sadayoshi Watanabe、Keiichi Ohtsuka、Shinobu Sato、Shigeori Takenaka

  DOI：10.1016/j.bmc.2010.10.056

  日期：2011.2

  Discrimination of phosphomonoesters and phosphodiesters of DNA was attempted with naphthalene diimide carrying two zinc-dipicolylamine (Dpa) units (1). The binding constant of 1 for a self-complementary octanucleotide was 1.3 x 10(6) M-1, while the value for the phosphorylated counterpart was 4.8 x 10(6) M-1. This fourfold increase in the binding constant seems to stem from higher affinity of the terminal monophosphate over the phosphodiesters of DNA as the fourth ligand for the metal in 1. Likewise, the binding constant of 1 for DNase I-treated calf thymus DNA (average size 200 bp) was twice as large as that for untreated DNA (1 kb), possibly because the terminal phosphate groups are five times abundant in the former. These findings provide a clue to developing a system where phosphomonoesters generated upon DNA nicking are discriminated specifically from intact phosphodiesters. (C) 2010 Elsevier Ltd. All rights reserved.
• Thermodynamics and kinetic studies in the binding interaction of cyclic naphthalene diimide derivatives with double stranded DNAs
  作者：Md. Monirul Islam、Satoshi Fujii、Shinobu Sato、Tatsuo Okauchi、Shigeori Takenaka

  DOI：10.1016/j.bmc.2015.05.046

  日期：2015.8

  Previously, we reported our investigations of the interaction between a cyclic naphthalene diimide derivative (cNDI 1) and double stranded DNA (dsDNA) (Bioorg. Med. Chem. 2014, 22, 2593). Here, we report the synthesis of the novel cNDI 2, which has shorter linker chains than cNDI 1. We performed comparative investigations of the interactions of both cNDI 1 and cNDI 2 with different types of dsDNA, including analysis of their thermodynamics and kinetics. Interactions between the cNDIs and calf thymus DNA (CT-DNA), poly[d(A-T)](2), or poly[d(G-C)](2) were explored by physicochemical and biochemical methods, including UV-Vis spectroscopy, circular dichroism (CD) spectroscopy, stopped-flow kinetics, and a topoisomerase I assay. Upon addition of cNDIs to CT-DNA, the existence of an induced CD signal at approximately the wavelength of the naphthalene diimide chromophore and unwinding of the DNA duplex, as detected by the topoisomerase I assay, revealed that cNDIs bound to the DNA duplex. As indicated by the steric constraint in the formation of the complex, bis-threading intercalation was the more favorable binding mode. UV-Vis spectroscopic titration of the cNDIs with DNA duplexes showed affinities on the order of 10(5)-10(6) M-1, with a stoichiometry of one cNDI molecule per four DNA base pairs. Thermodynamic parameters (Delta G, Delta H, and Delta S) based on the van't Hoff equation indicated that exothermic and entropy-dependent hydrophobic interactions played a major role in the reaction. Stopped-flow association and dissociation analysis showed that cNDI interactions with poly[d(G-C)](2) were more stable and had a slower dissociation rate than their interactions with poly[d(A-T)](2) and CT-DNA. Measurement of ionic strength indicated that electrostatic attraction is also an important component of the interaction between cNDIs and CT-DNA. Because of its longer linker chain, cNDI 1 showed higher binding selectivity, a more entropically favorable interaction, and much slower dissociation from dsDNA than cNDI 2. (C) 2015 Elsevier Ltd. All rights reserved.