1-bromomethyl-4-(4,7,10-tris(tert-butoxycarbonyl)-1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene | 257280-68-5

• 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: 1-bromomethyl-4-(4,7,10-tris(tert-butoxycarbonyl)-1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene
• 英文别名: 1-Bromomethyl-4-(4,7,10-tris(tert-butyloxycarbonyl)-1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene；1-[4'-(bromomethyl)benzyl]-4,7,10-tris(tert-butyloxycarbonyl)-1,4,7,10-tetraazacyclododecane；1,4,7-tri-tert-butyl 10-(4-(bromomethyl)benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7-tricarboxylate；1-(p-bromomethylbenzyl)-4,7,10-tris(tert-butyloxycarbonyl)-1,4,7,10-tetraazacyclododecane；1-bromomethyl-4-(4,7,10-tris(tert-butyloxycarbonyl)-1,4,7,10-tetraazacyclododecane-1-ylmethyl)benzene；Tritert-butyl 10-[[4-(bromomethyl)phenyl]methyl]-1,4,7,10-tetrazacyclododecane-1,4,7-tricarboxylate；tritert-butyl 10-[[4-(bromomethyl)phenyl]methyl]-1,4,7,10-tetrazacyclododecane-1,4,7-tricarboxylate
• CAS: 257280-68-5
• 化学式: C₃₁H₅₁BrN₄O₆
• 分子量: 655.673
• InChiKey: YANOSIMSAINMMB-UHFFFAOYSA-N

物化性质

• 熔点：
  69-71 °C
• 沸点：
  657.6±55.0 °C(Predicted)
• 密度：
  1.199±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  91.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-bromomethyl-4-(4,7,10-tris(tert-butoxycarbonyl)-1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene 在 氢溴酸 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 水 、 mineral oil 为溶剂， 反应 49.0h， 生成 1-(4-((1,4,7,10-tetraazacyclododecan-1-yl)methyl)benzyl)-1H-benzo[d]imidazole hydrobromide
  参考文献：
  名称：

  The synthesis and activities of novel mononuclear or dinuclear cyclen complexes bearing azole pendants as antibacterial and antifungal agents

  摘要：

  A series of novel compounds containing 1,4,7,10-tetraazacyclododecane and azoles were synthesized and characterized by (1)H NMR, MS and elemental analysis. Bioactive assay manifested that some target compounds, such as 11a, 11b and 11d, displayed good and broad spectrum antimicrobial activities with relative low MIC values against most of tested strains. These dinuclear complexes gave comparable or even better antimicrobial efficiencies than the reference drugs Fluconazole and Chloromycin. The result showed that the metal ions were the key factors to enhance the antimicrobial activities for mononuclear or dinuclear complexed in varying degrees. The interaction evaluation of compound 11b with bovine serum albumin (BSA) as an example was tested by fluorescence method. The thermodynamic parameters indicated that the hydrogen bonds and van der waals forces played the major roles in the strong association between dinuclear compound and BSA. The CCK-8 tests also confirmed the safeties of these dinuclear compounds in vitro.

  DOI：

  10.1016/j.ejmech.2014.07.075
• 作为产物：
  描述：

  1,4-二(溴甲基)苯 、 1,4,7-三叔丁氧羰基-1,4,7,10-四氮杂环十二烷 在 potassium carbonate 作用下， 以68.3%的产率得到1-bromomethyl-4-(4,7,10-tris(tert-butoxycarbonyl)-1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene
  参考文献：
  名称：

  具有咪唑或苯并咪唑悬垂物的新型 Zn(II) 大环配合物的合成、表征和分子识别

  摘要：

  已经合成了带有咪唑或苯并咪唑悬垂物的大环多胺 Zn(II) 单核和双核配合物，并通过紫外-可见光谱滴定确定了它们的结合常数。复合物的结合能力强于含有胞嘧啶（Cyt）的对照材料。双核复合物对Cyt的识别能力远高于其他碱基或核苷（如尿嘧啶、5-羟基甲基尿嘧啶、腺苷、胸苷和尿苷）；以间二甲苯基或吡啶基为接头的双核复合物的结合常数分别为 25,360 和 22,550 dm3 mol-1。

  DOI：

  10.3184/174751914x13894363997018

文献信息

• Small CyclenImidazolium-Containing Molecules and Their Interactions with DNA
  作者：Yang Zhang、Chun-Yan Li、Ji Zhang、Wen-Jing Yi、Xiao-Qi Yu

  DOI：10.1002/cbdv.201300242

  日期：2014.2

  Three small organic molecules containing different numbers of cyclen and imidazolium units were synthesized. Their interactions with plasmid DNA and their potential for gene delivery vectors were investigated. Agarose gel retardation and ethidium bromide exclusion assays revealed that these molecules can effectively condense DNA, and compounds with higher molecular weights are needed to lower w/w ratio

  合成了三个小有机分子，它们包含不同数量的环和咪唑单元。研究了它们与质粒DNA的相互作用以及潜在的基因传递载体。琼脂糖凝胶阻滞和溴化乙锭排阻分析表明，这些分子可以有效地凝结DNA，并且需要具有较高分子量的化合物以降低w / w比率才能完全缩合。动态光散射（DLS）和透射电子显微镜（TEM）表明，这些化合物可能与DNA形成纳米球形颗粒。此外，由10即10 / DNA形成的复合物可以在相对较高的NaCl（200 mM）浓度下从紧密状态部分释放DNA。在脂质1,2-二油酰基-sn-甘油-3-磷酸乙醇胺（DOPE）的存在下，10个可以将质粒DNA转移到BEL-7402细胞中。另外，这些化合物显示出比PEI 25 kDa低得多的细胞毒性。
• Novel cationic lipids possessing protonated cyclen and imidazolium salt for gene delivery
  作者：Qing-Dong Huang、Wen-Jing Ou、Hong Chen、Zhi-Hua Feng、Jing-Yi Wang、Ji Zhang、Wen Zhu、Xiao-Qi Yu

  DOI：10.1016/j.ejpb.2011.03.017

  日期：2011.8

  In this study, two novel protonated cyclen and imidazolium salt-containing cationic lipids differing only in their hydrophobic region (cholesterol or diosgenin) have been designed and synthesized for gene delivery. Cationic liposomes were easily prepared from each of these lipids individually or from the mixtures of each cationic lipid and dioleoylphosphatidyl ethanolamine (DOPE). Several studies including DLS, gel retardation assay, ethidium bromide intercalation assay, and TEM demonstrated that these amphiphilic molecules are able to bind and compact DNA into nanometer particles that could be used as non-viral gene delivery agents. Our results from in vitro transfection showed that in association with DOPE, two cationic lipids can induce effective gene transfection in HEK293 cells. Furthermore, the gene transfection efficiencies of two cationic lipids were dramatically increased in the presence of calcium ion (Ca2+). It is notable that the gene transfection abilities of two cationic lipids were maintained in the presence of 10% serum. Besides, different cytotoxicity was found for two lipoplexes. This study demonstrates that the title cationic lipids have large potential to be efficient non-viral gene vector. (C) 2011 Elsevier B.V. All rights reserved.
• Cationic Lipids Containing Cyclen and Ammonium Moieties as Gene Delivery Vectors
  作者：Qing-Dong Huang、Jiang Ren、Wen-Jing Ou、Yun Fu、Mao-Qiang Cai、Ji Zhang、Wen Zhu、Xiao-Qi Yu

  DOI：10.1111/j.1747-0285.2012.01355.x

  日期：2012.6

  In this study, two novel cationic lipids containing protonated cyclen and quaternary ammonium moieties were designed and synthesized as non‐viral gene delivery vectors. The structures of the two lipids differ in their hydrophobic region (cholesterol or diosgenin). Cationic liposomes were easily prepared from the lipids individually or from the mixtures of each cationic lipid and dioleoylphosphatidylethanolamine. Several studies including DLS, gel retardation assay, and ethidium bromide intercalation assay suggest that these amphiphilic molecules are able to bind and compact DNA into nanometer particles which can be used as non‐viral gene delivery agents. Our results from in vitro transfection show that in association with dioleoylphosphatidylethanolamine, two cationic lipids can induce effective gene transfection in human embryonic kidney 293 cells, although the gene transfection efficiencies of two cationic lipids were found to be lower than that of lipofectamine 2000TM. Besides, different cytotoxicity was found for two lipoplexes. This study demonstrates that the title cationic lipids have large potential to be efficient non‐viral gene vectors.
• The conjugates of uracil–cyclen Zn(II) complexes: Synthesis, characterization, and their interaction with plasmid DNA
  作者：Chuan-Qin Xia、Ning Jiang、Ji Zhang、Shan-Yong Chen、Hong-Hui Lin、Xin-Yu Tan、Yang Yue、Xiao-Qi Yu

  DOI：10.1016/j.bmc.2006.04.048

  日期：2006.8

  As an important nucleobase in RNA, uracil was introduced into the side chain of cyclen (1,4,7, 10-tetraazacyclododecane) by using phenylene dimethylene group as bridge. The target compounds 5 were obtained in high yields. Subsequent experiments demonstrated that the uracil-cyclen conjugates can bind Zn2+ cation rapidly in water, and the catalytic activities of their Zn(II) complexes 6 in DNA cleavage were also studied. The results showed that Zn(II) complexes can catalyze the cleavage of supercoiled DNA (pUC 19 plasmid DNA) (Form I) to produce nicked DNA (Form II and Form III) with high selectivity. In water solution, complex 6b may form a unique and stable supramolecular structure, which benefits the DNA cleavage process. (c) 2006 Elsevier Ltd. All rights reserved.
• Selective and Efficient Recognition of Thymidylylthymidine (TpT) by Bis(ZnII-cyclen) and Thymidylylthymidylylthymidine (TpTpT) by Tris(ZnII-cyclen) at Neutral pH in Aqueous Solution
  作者：Eiichi Kimura、Motoya Kikuchi、Hideyuki Kitamura、Tohru Koike

  DOI：10.1002/(sici)1521-3765(19991105)5:11<3113::aid-chem3113>3.0.co;2-l

  日期：1999.11.5

  Following our previous reports of a Zn-II-cyclen (1) complex (cyclen = 1,4,7,10-tetraazacyclododecane) that selectively recognizes imide-deprotonated thymidine (T-) to form a stable ternary complex, [T--(Zn-II-cyclen)] (2), in aqueous solution, we now report on the interaction of thymidylylthymidine (TpT) with a dimeric Zn-II-cyclen complex, which contains a p-xylyl spacer, bis(Zn-II-cyclen) (3), and thymidylylthymidylylthymidine (TpTpT) with a trimeric Zn-II-cyclen complex, which is linked by two alternate p-xylyl spacers, tris(Zn-II-cyclen) (4). These interactions were studied by H-1 NMR spectroscopy, UV spectrophotometric titration, potentiometric pH titration, isothermal calorimetric titration, and FAB-MS measurements. In relation to the 1:1 [T--(Zn-II-cyclen)] (2) complex (K-d = [uncomplexed T][uncomplexed 1]/[2] = 7.9 x 10(-4) M), far more stable 1:1 complexes of the dimeric and trimeric Zn-II-cyclen derivatives are formed with imide-deprotonated thymidine nucleotides: [T(-)pT(-)-bis(Zn-II-cyclen)] (5) (K-d = [uncomplexed TpT][uncomplexed :3]/[5]= 6.3 x 10(-7) M) and [T(-)pT(-)pT(-)-tris(Zn-II-cyclen)] (6) (K-d = [uncomplexed TpTpT] [uncomplexed 4]/[6] = 8.0 x 10(-10) M, determined by potentiometric pH titration) at pH 7.4 and 25 degrees C with I = 0.10 (NaNO3). For comparison, we also determined K-d values for 1:1 2'-deoxyguanylylthymidine (GpT, K-d = 1.3 x 10(-5) M), 2'-deoxycytidylylthymidine (CpT, K-d > 10(-4) M), and 2'-deoxyadenylylthymidine (ApT, K-d >10(-4) M) complexes with the bis(Zn-II-cyclen) (3) (K-d = [uncomplexed XpT] [uncomplexed 3]/[1:1 complex], determined by isothermal calorimetric titration), and for the Zn-II-(1-benzyl-1,4,7,10-tetraazacyclododecane) complex (16) of (Zn-II-benzylcyclen) (15) with T- (K-d = [uncomplexed T][uncomplexed 15]/[16]= 5.0 x 10(-4) M, determined by potentiometric pH titration) with I = 0.10 (NaNO3) at pH 7.4 and 25 degrees C. This paper represents the first quantitative assessment of stoichiometric and reversible interactions of multinuclear metal complexes with oligonucleotides, whereby the selective and efficient recognition of TpT by 3 and TpTpT by 4 were discovered.