[5-(2-{6-[(Bis-pyridin-2-ylmethyl-amino)-methyl]-pyridin-3-yl}-ethyl)-pyridin-2-ylmethyl]-bis-pyridin-2-ylmethyl-amine | 172696-99-0

• 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: [5-(2-{6-[(Bis-pyridin-2-ylmethyl-amino)-methyl]-pyridin-3-yl}-ethyl)-pyridin-2-ylmethyl]-bis-pyridin-2-ylmethyl-amine
• 英文别名: 1-[5-[2-[6-[[bis(pyridin-2-ylmethyl)amino]methyl]pyridin-3-yl]ethyl]pyridin-2-yl]-N,N-bis(pyridin-2-ylmethyl)methanamine
• CAS: 172696-99-0
• 化学式: C₃₈H₃₈N₈
• 分子量: 606.773
• InChiKey: ZUXRNEGUPROQCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  46
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  83.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  copper(II) perchlorate hexahydrate 、 [5-(2-{6-[(Bis-pyridin-2-ylmethyl-amino)-methyl]-pyridin-3-yl}-ethyl)-pyridin-2-ylmethyl]-bis-pyridin-2-ylmethyl-amine 以 甲醇 为溶剂， 以88%的产率得到
  参考文献：
  名称：

  双核铜配合物对 DNA 的高效和特异性链断裂：具有连接的三（2-吡啶基甲基）胺部分的配合物的比较反应性

  摘要：

  化合物 [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4) (D(1) = 双核配体与两个 tris(2-吡啶基甲基）胺单元通过 -CH(2)CH(2)- 桥在其 5-吡啶基位置共价连接）选择性促进寡核苷酸链上 DNA 的切割，该链从磨损的双链结构的 3' 侧延伸至两个残基的位点从交界处移位。反应的最低要求包括与切割位点相邻的 3' 突出端的 n（即第一个未配对）位置的鸟嘌呤和 5' 突出端的 n 位置的腺嘌呤。识别和链断裂与切割位点的核碱基无关。还原剂和分子氧的必要存在表明负责裂解的中间体是通过双核络合物的铜 (I) 形式激活分子氧而产生的。对自由基猝灭剂缺乏敏感性和高水平的断裂位点选择性表明一种不涉及可扩散自由基物种的机制。与单核类似物 [Cu(II)(TMPA)(H(2)O)](ClO(4))(2)（TMPA = tris（ 2-吡啶基甲基）胺）和 [Cu(OP)(2)](2+)（OP

  DOI：

  10.1021/ja020039z
• 作为产物：
  描述：

  6-(溴甲基)烟酸甲酯 在 lithium aluminium tetrahydride 、 氯化亚砜 、 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醚 、 氯仿 、 乙腈 为溶剂， 反应 60.01h， 生成 [5-(2-{6-[(Bis-pyridin-2-ylmethyl-amino)-methyl]-pyridin-3-yl}-ethyl)-pyridin-2-ylmethyl]-bis-pyridin-2-ylmethyl-amine
  参考文献：
  名称：

  双核铜配合物对 DNA 的高效和特异性链断裂：具有连接的三（2-吡啶基甲基）胺部分的配合物的比较反应性

  摘要：

  化合物 [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4) (D(1) = 双核配体与两个 tris(2-吡啶基甲基）胺单元通过 -CH(2)CH(2)- 桥在其 5-吡啶基位置共价连接）选择性促进寡核苷酸链上 DNA 的切割，该链从磨损的双链结构的 3' 侧延伸至两个残基的位点从交界处移位。反应的最低要求包括与切割位点相邻的 3' 突出端的 n（即第一个未配对）位置的鸟嘌呤和 5' 突出端的 n 位置的腺嘌呤。识别和链断裂与切割位点的核碱基无关。还原剂和分子氧的必要存在表明负责裂解的中间体是通过双核络合物的铜 (I) 形式激活分子氧而产生的。对自由基猝灭剂缺乏敏感性和高水平的断裂位点选择性表明一种不涉及可扩散自由基物种的机制。与单核类似物 [Cu(II)(TMPA)(H(2)O)](ClO(4))(2)（TMPA = tris（ 2-吡啶基甲基）胺）和 [Cu(OP)(2)](2+)（OP

  DOI：

  10.1021/ja020039z

文献信息

• Dinuclear cooper-based compounds and ligamd for nucleic acid scission and anticancer treatment
  申请人：Rokita E. Steven

  公开号：US20050090479A1

  公开（公告）日：2005-04-28

  The present invention is related to a novel method for splitting nucleic acids at specific points on a complementary nucleic acid segment using a dinuclear copper-based compound of Formula I. Additionally, the present invention is related to a novel treatment of cancer, tumors, and cancer cells using a dinuclear copper-based compound of Formula I or a naked ligand of formula II: (Formula I and II).

  本发明涉及一种使用式I的双核铜化合物，在互补核酸片段的特定点上分裂核酸的新方法。此外，本发明涉及使用式I的双核铜化合物或式II的裸配体（式I和II）的新型癌症、肿瘤和癌细胞治疗方法。
• Reversible O2 Binding to a Dinuclear Copper(I) Complex with Linked Tris(2-pyridylmethyl)amine Units: Kinetic-Thermodynamic Comparisons with Mononuclear Analogs
  作者：Dong-Heon Lee、Ning Wei、Narasimha N. Murthy、Zoltan Tyeklar、Kenneth D. Karlin、Susan Kaderli、Bernhard Jung、Andreas D. Zuberbuehler

  DOI：10.1021/ja00155a014

  日期：1995.12

  fajThe kinetics and thermodynamics of reaction of O-2 with copper(I) complexes can provide fundamental information relevant to chemical and biological systems. Using diode-array variable-temperature (180-296 K) stopped-flow kinetic methods, we report detailed information on the O-2 reactivity (in EtCN) of dicopper(I) complex [(D-1)Cu-2(I)(RCN)(2)](2+) (2a) (R = Me or Et) [D-1 = dinucleating ligand with a -CH2CH2- group linking two tris(2-pyridylmethyl)amine (TMPA) units at a 5-pyridyl position of each tetradentate moiety]. A comparative study of mononuclear complex [(TMPAE)Cu(RCN)li (1a') [TMPAE has a -C(O)OCH3 ester substituent in the 5-position of one pyridyl group of TMPA] has been carried out. The results are compared with data from the previously investigated complex [(TMPA)Cu(RCN)](+) (1a). The syntheses of D-1 and 2a-(ClO4)(2) are described; an X-ray structure reveals two pentacoordinate Cu(I) ions (Cu ... Cu = 11.70 Angstrom), each bound by the N-4-tetradentate and an EtCN molecule. Cyclic voltammetric data for 1a' and 2a are reported. At 193 K in EtCN, 2a reacts with O-2 (Cu/O-2 = 2:1, manometry) to produce an intensely purple colored solution of adduct [(D-1)Cu-2(O-2)](2+) (2c), lambda(max) = 540 nm (epsilon 11 100 M(-1) cm(-1)). This peroxo-dicopper(II) species reacts with PPh(3), liberating O-2 and producing the isolatable bis-phosphine adduct [(D')Cu-2(PPh(3))(2)](2+). The kinetic investigation provides spectral characterization of transient Cu/O-2 1:1 adducts generated upon oxygenation of cold solutions of 1a' or 2a. [(TMPAE)Cu(O-2)](+) (1b') forms reversibly (lambda(max) = 415 nm) with k(1) (8.2 +/- 0.4) x 10(3) M(-1) s(-1) and K-1 = k(1)/k(-1) = (284 +/- 9) M(-1) at 183 K, with Delta H-1 degrees (-32 +/- 1) kJ mol(-1), Delta S-1 degrees = (-127 +/- 3) J K-1 mol(-1). Two types of Cu(II)-O-2(-) complexes form in the reaction of 2a: a 2:1 open form (i.e., [(D-1)Cu-2(O-2)(EtCN)](2+), 2b) and a bis-O-2 2:2 open adduct (i.e., [(D-1)Cu-2(O-2)(2)](2+), 2b'). For the formation of 2b, k(1) (1.63 +/- 0.01) x 10(4) M(-1) s(-1) and K-1 = (2.03 +/- 0.04) x 10(3) M(-1) at 183 K. Complexes 2b and 2b' have identical spectroscopic properties (lambda(max) = 416 nm, epsilon = 4500 M(-1) cm(-1)) per Cu-O-2 unit, and their rate constants are statistically related. Intermediates 1b' and 2b further convert into (mu-peroxo)dicopper(II) [(2 Cu):(1 O-2)] complexes. [((TMPAE)Cu)(2)(O-2)](2+) (1c') (lambda(max) = 532 nm, epsilon = 9380 M(-1) cm(-1)) forms in a second-order reaction of 1b' with 1a' with K1K2 = (2.1 +/- 0.4) X 10(11) M(-2) at 183 K (Delta H(12)degrees = -77 +/- 1 kJ mol(-1) and Delta S(12)degrees = -203 +/- 5 J K-1 mol(-1)), while [D-1)Cu-2(O-2)](2+) (2c) (lambda(max) 540 nn, epsilon = 11 100 M(-1) cm(-1)) is generated from 2b in an intramolecular reaction, with k(2) = (3.51 +/- 0.05) x 10(1) s(-1) and k(on), = k(1)k(2)/k(-1) (7.1 +/- 0.2) x 10(4) M-l s(-1) (183 K). The overall formation of 2c is faster than for 1c' or [((TMPA)Cu)(2)(O-2)](2+) (1c) because of a more positive entropy of activation (Delta S-on(double dagger), = (-139 +/- 3) J K-1 mol(-1) for 2c vs Delta S-on(double dagger) = (-201 +/- 5) J K-1 mol(-1) for 1c). However, this significantly enhanced kinetic reactivity (for 2a --> 2c) is not reflected by an analogous increase in thermodynamic stability. [(D-1)Cu-2(O-2)](2+) (2c) is enthalpically less stable (Delta H(12)degrees = (-34.8 +/- 0.4) kJ mol(-1)) than Cu2O2 species 1c and 1c' (Delta H(12)degrees = -81 to -77 kJ mol(-1), respectively), which are formed from mononuclearprecursors. There is a substantially larger overall formation entropy for 2c [Delta S(12)degrees = (-89.3 +/- 1.5) J K-1 mol(-1) compared to -220 and -203 J K-1 mol(-1) for 1c and 1c', respectively] since Cu2O2 formation is an intramolecular, rather than intermolecular, process. Examination of other kinetic parameters and spectral differences provides complementary information that 2c has a strained structure. In fact, 2c is not the ultimate oxidation product: relief of steric constraints occurs at higher temperatures by a slow rearrangement (lambda(max) = 540 nm --> lambda(max) = 529 nm) producing (Cu2O2)(n) oligomers containing intermolecular Cu-O-2-Cu bonds. A particularly stable trimer species [((D-1)Cu-2(O-2))(3)](6+) (2d) was characterized, with Delta H-3 degrees (-153 kJ mol(-1))/3 = -51 KJ mol(-1) per Cu2O2 unit, intermediate between that seen for 2c, 1c, and 1c'. Thus, (peroxo)dicopper(II) complexes formed from mononuclear precursors are the most stable, while secondary rearrangements within intramolecularly formed Cu-2-O-2 complexes with dinucleating ligands can and do occur. Comparisons are made with relevant copper-dioxygen complexes, and the chemical and biological relevance of this chemistry is discussed.
• US7365060B2
  申请人：——

  公开号：US7365060B2

  公开（公告）日：2008-04-29
• Efficient and Specific Strand Scission of DNA by a Dinuclear Copper Complex:  Comparative Reactivity of Complexes with Linked Tris(2-pyridylmethyl)amine Moieties
  作者：Kristi J. Humphreys、Kenneth D. Karlin、Steven E. Rokita

  DOI：10.1021/ja020039z

  日期：2002.5.1

  [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4), is even capable of mediating efficient specific strand scission at concentrations where [Cu(OP)(2)](2+) does not detectably modify DNA. The unique coordination and reactivity properties of [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4) are critical for its efficiency and site selectivity since an analogue, [Cu(II)(2)(DO)(Cl(2))](ClO(4))(2), where DO is a dinucleating ligand

  化合物 [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4) (D(1) = 双核配体与两个 tris(2-吡啶基甲基）胺单元通过 -CH(2)CH(2)- 桥在其 5-吡啶基位置共价连接）选择性促进寡核苷酸链上 DNA 的切割，该链从磨损的双链结构的 3' 侧延伸至两个残基的位点从交界处移位。反应的最低要求包括与切割位点相邻的 3' 突出端的 n（即第一个未配对）位置的鸟嘌呤和 5' 突出端的 n 位置的腺嘌呤。识别和链断裂与切割位点的核碱基无关。还原剂和分子氧的必要存在表明负责裂解的中间体是通过双核络合物的铜 (I) 形式激活分子氧而产生的。对自由基猝灭剂缺乏敏感性和高水平的断裂位点选择性表明一种不涉及可扩散自由基物种的机制。与单核类似物 [Cu(II)(TMPA)(H(2)O)](ClO(4))(2)（TMPA = tris（ 2-吡啶基甲基）胺）和 [Cu(OP)(2)](2+)（OP