1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tris(1,1-dimethylethyl) ester hydrochloride

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tris(1,1-dimethylethyl) ester hydrochloride
• 英文别名: 1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic acid tri-tert-butyl ester hydrochloride；1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tert-butyl ester hydrochloride；1,4,7-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane hydrochloride；tris-(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane hydrochloride；Tert-butyl 2-[4,7-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetate;hydrochloride
• 化学式: C₂₆H₅₀N₄O₆*ClH
• 分子量: 551.167
• InChiKey: WIMNODORQPOLKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.94
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tris(1,1-dimethylethyl) ester hydrochloride 在 potassium iodide 叠氮基三甲基硅烷 、 二正丁基氧化锡 、 potassium carbonate 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 7.5h， 生成 [4,7-Bis-tert-butoxycarbonylmethyl-10-(1H-tetrazol-5-ylmethyl)-1,4,7,10-tetraaza-cyclododec-1-yl]-acetic acid tert-butyl ester
  参考文献：
  名称：

  具有四唑臂大环配体作为潜在的MRI造影剂的Gd（III）配合物的合成

  摘要：

  我们报告的合成和Gd（III）配合物与4（H 4 dotetra ）的复合物的性质，一种新型的混合悬挂臂大环配体，在N 5 O 3供体中包含一个四唑亚基，设置为潜在的磁共振成像（MRI） ）造影剂。

  DOI：

  10.1016/s0040-4039(01)02272-9
• 作为产物：
  描述：

  溴乙酸叔丁酯 、 轮环藤宁 在 氯仿 、 三乙胺 作用下， 以77%的产率得到1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tris(1,1-dimethylethyl) ester hydrochloride
  参考文献：
  名称：

  Tris N-烷基化环素的选择性一步合成

  摘要：

  提出了具有良好产率和空前选择性的三步N-烷基化环素的一般一步合成方法。Tris和1,4-bis N烷基化的环素是仅有的两种主要产物，被分离出来。此外，根据tris和1，4-双N-烷基化的环1和1a的单晶X射线结构，在该反应条件下，环上的一个氮原子可以被质子化，从而防止了其进一步的烷基化，从而得到最终提高了区域选择性。

  DOI：

  10.1016/j.tet.2004.04.086

文献信息

• A highly sensitive luminescent lectin sensor based on an α-d-mannose substituted Tb3+ antenna complex
  作者：Emma Martín Rodríguez、Nicoleta Bogdan、John A. Capobianco、Simonetta Orlandi、Marco Cavazzini、Chiara Scalera、Silvio Quici

  DOI：10.1039/c3dt33023k

  日期：——

  Lectin–carbohydrate interactions are the basis of many biological processes and essentially they constitute the language through which intercellular communications are codified. Thus they represent powerful tools in the examination and interpretation of changes that occur on cell surfaces during both physiological and, more importantly, pathological events. The development of optical techniques that exploit the unique properties of luminescent lanthanoid metal complexes in the investigation of lectin–carbohydrate recognition can foster research in the field of ratiometric biosensing and disease detection. Here we report the synthesis of a Tb3+-DO3A complex (Tb⊂1) bearing an α-D-mannose residue and the related study of binding affinity with concanavalin A (Con A) labeled with rhodamine-B-isothiocyanate (RITC-Con A). Luminescence spectroscopy and dynamic studies show changes in emission spectra that can be ascribed to a luminescence resonance energy transfer (LRET) from Tb⊂1 (donor) to RITC-Con A (acceptor). The binding constant value between the two species was found to be one order of magnitude larger than those previously reported for similar types of recognition. To the best of our knowledge this is the first example of the use of a pre-organized luminescent lanthanoid complex in the study of carbohydrate–protein interactions by LRET.

  凝集素与碳水化合物的相互作用是许多生物过程的基础，从根本上说，它们构成了细胞间通信的编码语言。因此，它们是研究和解释细胞表面在生理和更重要的病理过程中发生的变化的有力工具。在研究凝集素与碳水化合物的识别过程中，利用发光镧系金属复合物的独特性质开发光学技术，可以促进比率计量生物传感和疾病检测领域的研究。在此，我们报告了一种带有δ-D-甘露糖残基的 Tb3+-DO3A 复合物（Tbâ1）的合成及其与用罗丹明-B-异硫氰酸盐（RITC-Con A）标记的凝集素 A（Con A）的结合亲和力的相关研究。发光光谱和动态研究显示，发射光谱的变化可归因于 Tbâ1 （供体）到 RITC-Con A（受体）之间的发光共振能量转移（LRET）。研究发现，这两种物质之间的结合常数比以前报告的类似识别类型的结合常数要大一个数量级。据我们所知，这是第一个利用预组织发光镧系元素复合物通过 LRET 研究碳水化合物与蛋白质相互作用的例子。
• Highly homogeneous, transparent and luminescent SiO₂glassy layers containing a covalently bound tetraazacyclododecane–triacetic acid–Eu(<scp>iii</scp>)–acetophenone complex
  作者：Silvio Quici、Marco Cavazzini、Maria Concetta Raffo、Lidia Armelao、Gregorio Bottaro、Gianluca Accorsi、Cristiana Sabatini、Francesco Barigelletti

  DOI：10.1039/b514409d

  日期：——

  The preparation of sol–gel glasses is described wherein highly stable Eu(III) centres are anchored to the silica glass upon acidic hydrolysis and by using tetraethylorthosilicate (TEOS) as a silica source. The complex employed is Eu·1 and is obtained from bipartite ligand 1, which features a DO3A macrocycle as a hosting unit for the Eu(III) centre, a methoxy-acetophenone unit as an antenna chromophore, and an alkyl chain bearing one primary hydroxy group (DO3A is 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid). Eu·1 is linked to the forming silica glass through the –OH groups and a uniform distribution of the luminescent centres is obtained, as indicated by results from secondary ion mass spectrometry in-depth profiling. The luminescent efficiency of the Eu(III) centres in the solid matrix is evaluated to be 10%, which is comparable to that of Eu·1 in water solution and of a convenient reference complex, Eu·2 (2 is a ligand featuring the same hosting and antenna functionalities of 1, wherein the –OH residue is replaced by an unreactive group, a benzoylmethyl residue). A discussion is given of the photophysical properties exhibited by the complexes in the film and in solution.

  本研究描述了如何制备溶胶玻璃，通过酸性水解和使用四乙基正硅酸盐（TEOS）作为二氧化硅源，将高度稳定的 Eu（III）中心锚定到二氧化硅玻璃上。所使用的复合物为 EuÂ-1 ，由双配体 1 制得，其特点是一个 DO3A 大环作为 Eu（III）中心的承载单元，一个甲氧基苯乙酮单元作为天线发色团，以及一个带有一个伯羟基的烷基链（DO3A 为 1,4,7,10-四氮杂环十二烷-1,4,7-三乙酸）。EuÂ-1通过âOH基团与成型的硅玻璃相连，发光中心分布均匀，二次离子质谱深度分析结果表明了这一点。经评估，固体基质中 Eu（III）中心的发光效率为 10%，与水溶液中的 EuÂ-1 和方便的参考配合物 EuÂ-2 的发光效率相当（2 是一种配体，具有与 1 相同的寄主和天线功能，其中的âOH 残基被一个非活性基团（苯甲酰甲基残基）取代）。本文讨论了络合物在薄膜和溶液中表现出的光物理特性。
• Development of Ln(III) Derivatives as 19F Parashift Probes
  作者：Megan A. Kaster、Michael A. Caldwell、Thomas J. Meade

  DOI：10.1021/acs.inorgchem.4c00652

  日期：2024.5.27

  LnL 19F parashift probes. We evaluated trans-gadolinium paramagnetic lanthanides compared to diamagnetic YL for 19F chemical shift and relaxation rate enhancement. The paramagnetic contribution to chemical shift (δPCS) for paramagnetic LnL exhibited either shifts to lower frequency (δPCS < 0 for TbL, DyL, and HoL) or shifts to higher frequency (δPCS > 0 for ErL, TmL, and YbL) compared to YL 19F spectroscopic

  具有顺磁位移报告核的19 F parashift 探针为开发分子成像探针提供了有吸引力的平台。这些探针能够使用直接检测技术对分子疾病标记物进行比例检测。在这里，我们描述了一系列三价镧系元素 (Ln(III)) 复合物，它们是临床批准的 MR 造影剂 (CA) ProHance 的结构类似物，以获得LnL 19 F parashift 探针。我们评估了反磁性 YL 与反磁性YL相比的反式钆顺磁性镧系元素的19 F 化学位移和弛豫率增强情况。顺磁LnL的顺磁对化学位移 (δ PCS ) 的贡献要么向较低频率移动（对于TbL 、 DyL和HoL ，δ PCS < 0 ），要么向较高频率移动（对于ErL 、 TmL和YbL ，δ PCS > 0 ）与YL 19 F 光谱信号相比。零回波时间脉冲序列使DyL的灵敏度比YL提高了 56 倍，同时开发具有快速延迟时间和采集时间的探针特异性脉冲序列，使DyL的检测限提高了
• In Vitro Imaging and Human Serum Albumin Responsive Dimeric Lanthanide DO3A Complex
  作者：Yuen On Fung、Wanqing Wu、Chi-Tung Yeung、Hoi-Kuan Kong、Kenny Kam-Cheng Wong、Wai-Sum Lo、Ga-Lai Law、Ka-Leung Wong、Chi-Kong Lau、Chi-Sing Lee、Wing-Tak Wong

  DOI：10.1021/ic2004672

  日期：2011.6.20

  Two series of dimeric DO3A (1,4,7,10-tetraazacyclodecane-1,4,7-triacetate) lanthanide complexes (LnL(1)-LnL(2), Ln = Eu, Gd, and Tb) have been synthesized with two different bridged chromophores. The X-ray structures of dimeric LnL(1) (Ln = Gd and Tb) complexes show that each metal ion has nine coordination numbers with eight directly bound donor atoms of the ligand and one oxygen donor from the water molecule. Photophysical measurements indicate that the bridged antenna in LnL(2) gives a higher efficiency than that of LnL(1) and is responsive to the protein Human Serum Albumin (HSA), giving an f-f luminescence signal enhancement with a binding constant log K = 4.84. In vitro imaging of EuL(1) and EuL(2) in HeLa cells has been recorded, and EuL(2) has demonstrated a higher rate of cellular uptake and low cytotoxicity (IC(50) = 3 mM).
• Non-covalent Conjugates between Cationic Polyamino Acids and GdIII Chelates: A Route for Seeking Accumulation of MRI-Contrast Agents at Tumor Targeting Sites
  作者：Silvio Aime、Mauro Botta、Elena Garino、Simonetta Geninatti Crich、Giovanni Giovenzana、Roberto Pagliarin、Giovanni Palmisano、Massimo Sisti

  DOI：10.1002/1521-3765(20000717)6:14<2609::aid-chem2609>3.0.co;2-s

  日期：2000.7.17

  Three novel Gd chelates containing on their external surface pendant phosphonate and carboxylate groups, which promote the interaction with the positively charged groups of polyornithine and polyarginine, have been synthesized. Their solution structures have been assessed on the basis of H-1- and P-31-NMR spectra of the Eu and Yb analogues. A thorough investigation of the relaxometric (H-1 and O-17) Properties of the Gd chelates has been carried out and the observed relaxivities have been accounted for the sum of three contributions arising from water molecules in the first, second, and outer coordination layers, respectively. It has been found that the occurrence of a tight second coordination coating renders the dissociation of the water molecule directly coordinated to the Gd ion more difficult. The binding interactions between the negatively charged Gd chelates and the positively charged groups of polyornithine (ca. 140 residues) and polyarginine (ca. 204 residues) have been evaluated by means of the proton relaxation enhancement (PRE) method. Although the binding interaction decreases markedly in the presence of competitive anions in the solution medium, the affinity is strong enough that in blood serum it is possible to meet the conditions where most of the chelate is bound to the polyamino acid substrate. On this basis one may envisage a novel route for a MRI location of tumors as it is known that positively charged polyamino acids selectively bind to tumors having a greater negative charge than non-tumor cells.