3,7,10,13,17,21,24,27-Octamethyl-30,34-dioxa-7,10,13,21,24,27-hexazatetracyclo[13.13.7.05,29.019,35]pentatriaconta-1(29),2,4,15,17,19(35)-hexaene | 1121856-92-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,7,10,13,17,21,24,27-Octamethyl-30,34-dioxa-7,10,13,21,24,27-hexazatetracyclo[13.13.7.05,29.019,35]pentatriaconta-1(29),2,4,15,17,19(35)-hexaene
• 英文别名: 3,7,10,13,17,21,24,27-octamethyl-30,34-dioxa-7,10,13,21,24,27-hexazatetracyclo[13.13.7.05,29.019,35]pentatriaconta-1(29),2,4,15,17,19(35)-hexaene
• CAS: 1121856-92-5
• 化学式: C₃₅H₅₈N₆O₂
• 分子量: 594.885
• InChiKey: PLGZHTVDJMJDQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  43
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  37.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  zinc perchlorate 、 3,7,10,13,17,21,24,27-Octamethyl-30,34-dioxa-7,10,13,21,24,27-hexazatetracyclo[13.13.7.05,29.019,35]pentatriaconta-1(29),2,4,15,17,19(35)-hexaene 以 甲醇 为溶剂， 以65%的产率得到[Zn2^L2(ClO4)2](ClO4)2
  参考文献：
  名称：

  DNA targeting polyaza macrobicyclic dizinc(ii) complexes promoting high in vitro caspase dependent anti-proliferative activity against human carcinoma cancer cells

  摘要：

  合成并表征了一系列大双环二锌(II)配合物[Zn2L1-2B](ClO4)4（1-6）（L1-2为多氮大双环双核配体，B为N,N-供体杂环碱（即2,2′-联吡啶（bipy）和1,10-菲罗啉（phen））。研究了这些复合物的 DNA 和蛋白质结合、DNA 水解和抗癌活性。通过光谱技术，包括吸收、荧光和 CD 光谱，研究了复合物 1-6 与小牛胸腺 DNA 的相互作用。研究发现，这些复合物的 DNA 结合常数范围为 2.80 × 105 至 5.25 × 105 M-1，结合亲和力依次为：3 > 6 > 2 > 5 > 6 > 3 > 6 > 2 > 5 > 6：3 > 6 > 2 > 5 > 1 > 4.在厌氧和有氧条件下，所有的二锌(II)配合物 1-6 都能有效地促进质粒 pBR322 DNA 的水解裂解。在生理条件下，3 和 6 促进 DNA 水解的动力学数据给出了观察到的速率常数（kobs），分别为 5.56 ± 0.1 和 5.12 ± 0.2 h-1，与未催化的 dsDNA 反应相比，速率加快了 107 倍。值得注意的是，大环二锌(II)复合物 1-6 能结合并裂解牛血清白蛋白（BSA），有效促进 HeLa 和 BeWo 癌细胞依赖 caspase-3 和 caspase-9 死亡。癌细胞裂解物和培养基内容物中的乳酸脱氢酶水平进一步证实了复合物的细胞毒性。

  DOI：

  10.1039/c2dt31094e

文献信息

• DNA binding, DNA hydrolysis and phosphatase-like activity of new macrobicyclic dicopper(II) complexes
  作者：S. Anbu、M. Kandaswamy、M. Selvaraj

  DOI：10.1016/j.poly.2011.10.041

  日期：2012.2

  A new class of macrobicyclic dicopper(II) complexes, [Cu2L1-2B](ClO4)(4) (1-4) where L1-2 are polyaza macrobicyclic binucleating ligands and B is a N,N-donor heterocyclic base (viz. 2,2-bipyridyl (bipy) and 1,10-phenanthroline (phen)), have been prepared and characterized. The redox, catalytic, DNA binding and DNA cleavage properties were also studied. They exhibit a quasi-reversible cyclic voltammetric response near -0.5 V versus Ag/AgCl in CH3CN-0.1 M TBAP, assignable to the Cu-2(II)/Cu-2(I) redox couple. The initial rate values for the hydrolysis of 4-nitrophenylphosphate to 4-nitrophenolate by the dicopper(II) complexes 1-4 are 1.3 x 10(-5), 0.9 x 10(-5), 4.3 x 10(-4) and 3.5 x 10(-4) M s(-1), respectively. Complexes 2 and 4 show a good binding propensity to calf thymus DNA, giving binding constant values in the range 1.02 x 10(5)-8.32 x 10(5) M-1. The binding site size and viscosity data suggest a DNA intercalative and/or groove binding nature of the complexes. The complexes display significant hydrolytic cleavage of supercoiled pBR322 DNA at pH 7.2 and 37 degrees C. The hydrolytic cleavage of DNA by the complexes is supported by the evidence from free radical quenching and T4 ligase ligation. The pseudo Michaelis-Menton kinetic parameters k(cat) = 5.23 +/- 0.3 h(-1) and K-M = 6.42 x 10(-3) M were obtained for complex 4. (C) 2011 Elsevier Ltd. All rights reserved.
• DNA targeting polyaza macrobicyclic dizinc(ii) complexes promoting high in vitro caspase dependent anti-proliferative activity against human carcinoma cancer cells
  作者：Sellamuthu Anbu、Rajendran Ravishankaran、Anjali A. Karande、Muthusamy Kandaswamy

  DOI：10.1039/c2dt31094e

  日期：——

  A series of macrobicyclic dizinc(II) complexes [Zn2L1–2B](ClO4)4 (1–6) have been synthesized and characterized (L1–2 are polyaza macrobicyclic binucleating ligands, and B is the N,N-donor heterocyclic base (viz. 2,2′-bipyridine (bipy) and 1,10-phenanthroline (phen)). The DNA and protein binding, DNA hydrolysis and anticancer activity of these complexes were investigated. The interactions of complexes 1–6 with calf thymus DNA were studied by spectroscopic techniques, including absorption, fluorescence and CD spectroscopy. The DNA binding constant values of the complexes were found to range from 2.80 × 105 to 5.25 × 105 M−1, and the binding affinities are in the following order: 3 > 6 > 2 > 5 > 1 > 4. All the dizinc(II) complexes 1–6 are found to effectively promote the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic conditions. Kinetic data for DNA hydrolysis promoted by 3 and 6 under physiological conditions give observed rate constants (kobs) of 5.56 ± 0.1 and 5.12 ± 0.2 h−1, respectively, showing a 107-fold rate acceleration over the uncatalyzed reaction of dsDNA. Remarkably, the macrobicyclic dizinc(II) complexes 1–6 bind and cleave bovine serum albumin (BSA), and effectively promote the caspase-3 and caspase-9 dependent deaths of HeLa and BeWo cancer cells. The cytotoxicity of the complexes was further confirmed by lactate dehydrogenase enzyme levels in cancer cell lysate and content media.

  合成并表征了一系列大双环二锌(II)配合物[Zn2L1-2B](ClO4)4（1-6）（L1-2为多氮大双环双核配体，B为N,N-供体杂环碱（即2,2′-联吡啶（bipy）和1,10-菲罗啉（phen））。研究了这些复合物的 DNA 和蛋白质结合、DNA 水解和抗癌活性。通过光谱技术，包括吸收、荧光和 CD 光谱，研究了复合物 1-6 与小牛胸腺 DNA 的相互作用。研究发现，这些复合物的 DNA 结合常数范围为 2.80 × 105 至 5.25 × 105 M-1，结合亲和力依次为：3 > 6 > 2 > 5 > 6 > 3 > 6 > 2 > 5 > 6：3 > 6 > 2 > 5 > 1 > 4.在厌氧和有氧条件下，所有的二锌(II)配合物 1-6 都能有效地促进质粒 pBR322 DNA 的水解裂解。在生理条件下，3 和 6 促进 DNA 水解的动力学数据给出了观察到的速率常数（kobs），分别为 5.56 ± 0.1 和 5.12 ± 0.2 h-1，与未催化的 dsDNA 反应相比，速率加快了 107 倍。值得注意的是，大环二锌(II)复合物 1-6 能结合并裂解牛血清白蛋白（BSA），有效促进 HeLa 和 BeWo 癌细胞依赖 caspase-3 和 caspase-9 死亡。癌细胞裂解物和培养基内容物中的乳酸脱氢酶水平进一步证实了复合物的细胞毒性。