cis-[Ti(isopropoxide)2((CH2N(CH3)CH2C6H2(CH3)2O)2)] | 914490-79-2

• 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: cis-[Ti(isopropoxide)2((CH2N(CH3)CH2C6H2(CH3)2O)2)]
• 英文别名: [Ti((O(CH3)2C6H2CH2N(CH3)CH2)2)(OiPr)2]；(6,6'-((ethane-1,2-diylbis(methylazanediyl))bis(methylene))bis(2,4-dimethyl-phenol))-diisopropoxide titanium(IV)
• CAS: 914490-79-2
• 化学式: C₂₈H₄₄N₂O₄Ti
• 分子量: 520.548
• InChiKey: IOHKLKJCGLYMQE-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  5.92
• 重原子数：
  35.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  43.4
• 氢给体数：
  0.0
• 氢受体数：
  6.0

文献信息

• Heptacoordinate Heteroleptic Salan (ONNO) and Thiosalan (OSSO) Titanium(IV) Complexes: Investigation of Stability and Cytotoxicity
  作者：Martin Grützke、Tiankun Zhao、Timo A. Immel、Thomas Huhn

  DOI：10.1021/acs.inorgchem.5b00690

  日期：2015.7.20

  heptacoordinate titanium(IV) complexes were synthesized based on the concept of hetero-bis-chelate stabilization of salan (ONNO) and thiosalan (OSSO) titanium(IV)alkoxides with 2,6-pyridinedicarboxylic acid (dipic) and derivatives thereof. The resulting compounds were investigated in a solid by X-ray diffraction and in solution by NMR spectroscopy. A thiosalan (OSSO) titanium(IV) complex could be isolated

  根据salan（ONNO）和thiOSalan（OSSO）钛（IV）烷氧基与2,6-吡啶二甲酸（dipic）及其衍生物的异双螯合稳定概念，合成了七种七配位钛（IV）配合物。通过X射线衍射在固体中和通过NMR光谱在溶液中研究所得化合物。可以分离出一个硫代（OSSO）钛（IV）配合物，并通过1 H NMR光谱显示了其通过二元构象的构象稳定性，即使在室温下，也能导致无通量的行为。通过紫外可见监测的水解研究（> 5 Mio），在pH 1.9、6.8和12.1下评估了选定配合物的稳定性。当量的水。即使在pH 12.1时，[L 1 Ti（dipic）1 ]仍显示出t超过2天的1/2。在两种人类癌细胞系中研究了所有化合物的细胞毒性。除[L 4 Ti（dipic）1 ]外，所有测试的化合物均达到顺铂范围的IC 50值，事实证明该化合物无毒。因此，二斜肽的功能性被很好地耐受，并且既不影响杂合剂复合物的稳定性也没有细胞毒性。
• Design, Synthesis, Computational, and Preclinical Evaluation of natTi/45Ti-Labeled Urea-Based Glutamate PSMA Ligand
  作者：Kristina Søborg Pedersen、Christina Baun、Karin Michaelsen Nielsen、Helge Thisgaard、Andreas Ingemann Jensen、Fedor Zhuravlev

  DOI：10.3390/molecules25051104

  日期：——

  Despite promising anti-cancer properties in vitro, all titanium-based pharmaceuticals have failed in vivo. Likewise, no target-specific positron emission tomography (PET) tracer based on the radionuclide 45Ti has been developed, notwithstanding its excellent PET imaging properties. In this contribution, we present liquid–liquid extraction (LLE) in flow-based recovery and the purification of 45Ti, computer-aided design, and the synthesis of a salan-natTi/45Ti-chelidamic acid (CA)-prostate-specific membrane antigen (PSMA) ligand containing the Glu-urea-Lys pharmacophore. The compound showed compromised serum stability, however, no visible PET signal from the PC3+ tumor was seen, while the ex vivo biodistribution measured the tumor accumulation at 1.1% ID/g. The in vivo instability was rationalized in terms of competitive citrate binding followed by Fe(III) transchelation. The strategy to improve the in vivo stability by implementing a unimolecular ligand design is presented.

  尽管钛基制药在体外表现出有希望的抗癌特性，但所有基于钛的制药品在体内均失败。同样地，尽管45Ti放射性核素具有出色的PET成像特性，但尚未开发出基于其的靶向特异性正电子发射断层扫描（PET）示踪剂。在本文中，我们介绍了基于流动液-液萃取（LLE）的45Ti回收和纯化、计算机辅助设计以及合成含有Glu-urea-Lys药效团的salan-natTi/45Ti-chelidamic acid（CA）-前列腺特异性膜抗原（PSMA）配体。该化合物显示出受到血清稳定性的影响，然而，未观察到来自PC3+肿瘤的PET信号，而外体分布测量显示肿瘤积累为1.1% ID/g。体内不稳定性是通过竞争性柠檬酸结合，随后是Fe（III）跨螯合来解释的。本文介绍了通过实施单分子配体设计来提高体内稳定性的策略。
• Active Cytotoxic Reagents Based on Non-metallocene Non-diketonato Well-Defined <i>C</i>₂-Symmetrical Titanium Complexes of Tetradentate Bis(phenolato) Ligands
  作者：Michal Shavit、Dani Peri、Cesar M. Manna、Jacob S. Alexander、Edit Y. Tshuva

  DOI：10.1021/ja0753086

  日期：2007.10.1

  of non-Cp-based non-diketonato-based C2-symmetrical octahedral Ti(IV) complexes of dianionic diamine bis(phenolato) ligands, which are conveniently obtained as single isomers in quantitative yields, leads to appreciable cytotoxicity against colon and ovarian cells with a non-transferrin-dependent cell penetration mechanism. The ligand structural features including steric demands, symmetry, and aromaticity

  一类新的基于非 Cp 的非二酮基 C2 对称八面体 Ti（IV）配合物的双阴离子二胺双（苯酚）配体，它们可以作为单一异构体以定量产率方便地获得，对结肠和结肠产生可观的细胞毒性。具有非转铁蛋白依赖性细胞渗透机制的卵巢细胞。配体结构特征（包括空间需求、对称性和芳香性）强烈影响活性，支持其在生物作用机制中的作用。
• Facile synthesis of [ONON] type titanium(IV) bis-chelated complexes in alcoholic solvents and evaluation of anti-tumor activity
  作者：Tiankun Zhao、Peng Wang、Nan Liu、Shanjia Li、Mingjun Yang、Zhongduo Yang

  DOI：10.1016/j.jinorgbio.2022.111925

  日期：2022.10

  Most [ONON] type Ti(IV) complexes exhibit selectively enhanced inhibition activity against Hep G2 cells in comparison with Salan Ti(IV) complexes. Among which, the inhibitory activity of 2 t (IC50: 0.15 ± 0.1 μM) against Hep G2 cells is about 80 times enhanced than that of cisplatin (IC50: 12.4 ± 1.2 μM). The [ONON] type Ti(IV) complexes slowly released nontoxic phenolato ligands in presence of large

  通过使用正丙醇作为溶剂并使用 H 2 O 进行分离的高效方案，合成了由 2,6-吡啶二羧酸稳定的新型抗肿瘤二氨基-双-（苯酚）[ONON] 型钛(IV)配合物。总共合成了 20 种 [ONON] 型和 2 种 Salan Ti (IV)双螯合配合物，产率从 68% 到 96%。使用 Ti(O i Pr) 4或 TiCl 4作为起始材料，所有反应都可以在 80 °C 的 1.5 分钟内完成。与 Salan Ti 相比，大多数 [ONON] 型 Ti (IV)复合物对 Hep G2 细胞表现出选择性增强的抑制活性 （四）配合物。其中，2t (IC 50 : 0.15 ± 0.1 μM)对Hep G2细胞的抑制活性比 顺铂( IC 50 : 12.4 ± 1.2 μM)增强约80倍。[ONON] 型 Ti (IV)配合物在存在大量水性介质的情况下缓慢释放无毒的酚酸配体，并且基于金属摄取分析提出了这些
• Synthesis and X-ray structure analysis of a heptacoordinate titanium(iv)-bis-chelate with enhanced in vivo antitumor efficacy
  作者：Timo A. Immel、Martin Grützke、Anne-Katrin Späte、Ulrich Groth、Peter Öhlschläger、Thomas Huhn

  DOI：10.1039/c2cc31624b

  日期：——

  Chelate stabilization of a titanium(IV)-salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.

  通过与2，6-吡啶二羧酸（二甲基）进行配体交换而使钛（IV）-烷氧基烷氧基化物的螯合稳定化导致七配位络合物3，其不具有氧化还原活性，在硅胶上稳定并且具有增加的水稳定性。3在HeLa S3和Hep G2中具有高毒性，并且在小鼠宫颈癌模型中具有增强的抗肿瘤功效。