dichlororuthenium(II) (p-cymene)(1,3,5-triaza-7-phosphaadamantane) | 372948-28-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: dichlororuthenium(II) (p-cymene)(1,3,5-triaza-7-phosphaadamantane)
• 英文别名: RAPTA-C；Ru(η⁶-p-cymene)Cl₂(1,3,5-triaza-7-phosphaadamantane)；[RuCl₂(η⁶-p-cymene)(PTA)]；[RuCl₂(p-cymene)(1,3,5-triaza-7-phosphaadamantane)]；[RuCl₂(η⁶-p-cymene)(1,3,5-triaza-7-phosphaadamantane)]；dichloro[(1,2,3,4,5,6-η)-1-methyl-4-(1-methylethyl)benzene](1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane-κP7)ruthenium(II)；[Ru(η⁶-p-cymene)(1,3,5-triaza-7-phosphaadamantane)Cl₂]；[RuCl₂(η⁶-p-cymene)(κP-PTA)]；Ru(η⁶-p-cymene)Cl₂(PTA)；[RuCl₂(p-cymene)(PTA)]；1-methyl-4-propan-2-ylbenzene;ruthenium(2+);1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane;dichloride
• CAS: 372948-28-2
• 化学式: C₁₆H₂₆Cl₂N₃PRu
• 分子量: 463.352
• InChiKey: WVGPLKFVBMQDOG-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  4.66
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  9.7
• 氢给体数：
  0
• 氢受体数：
  3

制备方法与用途

RAPTA-C可通过线粒体和p53/JNK途径诱导EAC细胞凋亡。

反应信息

• 作为反应物：
  描述：

  dichlororuthenium(II) (p-cymene)(1,3,5-triaza-7-phosphaadamantane) 、 sodium oxalate 以 水 、 sodium chloride 为溶剂， 生成 Oxali-RAPTA-C
  参考文献：
  名称：

  Development of Organometallic Ruthenium−Arene Anticancer Drugs That Resist Hydrolysis

  摘要：

  With a view to develop drugs that could resist hydrolysis in aqueous media, organometallic arene-capped ruthenium- (II) 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (RAPTA) complexes bearing chelating carboxylate ligands have been prepared and studied. The new complexes, Ru(eta(6)-cymene)(PTA)(C2O4) (1) and Ru(eta(6)-cymene)(PTA)(C6H6O4) (2), were found to be highly soluble and kinetically more stable than their RAPTA precursor that contains two chloride ligands in place of the carboxylate ligands. They were also able to resist hydrolysis in water and exhibited significantly lower pK(a) values. Importantly, they showed a similar order of activity in inhibiting cancer cell-growth proliferation (as determined by in vitro assays) and exhibited oligonucleotide binding characteristics (as evidenced by matrix-assisted laser desorption ionization mass spectrometry) similar to those of the RAPTA precursor, hence realizing a strategy for developing a new generation of stable and highly water-soluble RAPTA adducts.

  DOI：

  10.1021/ic061008y
• 作为产物：
  描述：

  [RhCl2(p-cymene)]2 、 1,3,5-三氮杂-7-磷杂金刚烷 以 甲醇 为溶剂， 反应 3.0h， 生成 dichlororuthenium(II) (p-cymene)(1,3,5-triaza-7-phosphaadamantane)
  参考文献：
  名称：

  Enhanced Delivery of the RAPTA-C Macromolecular Chemotherapeutic by Conjugation to Degradable Polymeric Micelles

  摘要：

  Macromolecular ruthenium complexes are a promising avenue to better and more selective chemotherapeutics. We have previously shown that RAPTA-C [RuCl2(p-cymene)-(PTA)], with the water-soluble 1,3,5-phosphaadamantane (PTA) ligand, could be attached to a polymer moiety via nucleophilic substitution of an available iodide with an amide in the PTA ligand. To increase the cell uptake of this macromolecule, we designed an amphiphilic block copolymer capable of self-assembling into polymeric micelles. The block copolymer was prepared by ring-opening polymerization of D,L-lactide (3,6-dimethy1-1,4-dioxane-2,5-dione) using a RAFT agent with an additional hydroxyl functionality, followed by the RAFT copolymerization of 2-hydroxyethyl acrylate (HEA) and 2-chloroethyl methacrylate (CEMA). The Finkelstein reaction and reaction with PTA led to polymers that can readily react with the dimer of RuCl2(p-cymene) to create a macromolecular RAPTA-C drug. RAPTA-C conjugation, micellization, and subsequent cytotoxicity and cell uptake of these polymeric moieties was tested on ovarian cancer A2780, A2780cis, and Ovcar-3 cell lines. Confocal microscopy images confirmed cell uptake of the micelles into the lysosome of the cells, indicative of an endocytic pathway. On average, a 10-fold increase in toxicity was found for the macromolecular drugs when compared to the RAPTA-C molecule. Furthermore, the cell uptake of ruthenium was analyzed and a significant increase was found for the micelles compared to RAPTA-C. Notably, micelles prepared from the polymer containing fewer HEA units had the highest cytotoxicity, the best cell uptake of ruthenium and were highly effective in suppressing the colony-forming ability of cells.

  DOI：

  10.1021/bm4013919
• 作为试剂：
  描述：

  4-乙酰氧基苯甲酸 、 1-己炔 在 dichlororuthenium(II) (p-cymene)(1,3,5-triaza-7-phosphaadamantane) 、 sodium carbonate 作用下， 以 甲苯 为溶剂， 反应 0.5h， 生成 (Z)-1-hexen-2-yl 4-acetoxybenzoate 、 (E)-1-hexen-2-yl 4-acetoxybenzoate 、 hex-1-en-2-yl 4-acetoxybenzoate
  参考文献：
  名称：

  Catalytic activity assessment of [RuCl2 (p-cymene) (PTA)] in the synthesis of enol esters

  摘要：

  通过催化[RuCl2 (p-cymene) (PTA)]复合物将羧酸加成到1-己炔，生成烯醇酯。因此，选择性获得了马尔科尼科夫加成型产物。160°C的微波辅助反应确认了温度的影响，30分钟内获得了定量到优异的产率。催化剂负载测试证明[RuCl2 (p-cymene) (PTA)]复合物可以高效地以1/1500的比例与羧酸结合，提供了1500的单位转化数（TON）。

  DOI：

  10.1007/s13738-015-0732-7

文献信息

• Facile synthesis of [Ru(η2-O2CO)(pta)(η6-p-cymene)], an outstandingly active Ru(II) half-sandwich complex for redox isomerization of allylic alcohols
  作者：Evelin Bolyog-Nagy、Antal Udvardy、Ágnes Barczáné-Bertók、Ferenc Joó、Ágnes Kathó

  DOI：10.1016/j.ica.2016.06.041

  日期：2017.1

  transposition of allylic alcohols, such as oct-1-en-3-ol in aqueous media. The isomerisation of oct-1-en-3-ol to octan-3-one took place only at pH > 10 buffer solutions or in the presence of alkali metal carbonates. The aqueous solution of “in situ” catalyst ([RuCl2(pta)(η6-p-cymene)] + 2 eq Na2CO3) could be reused in the biphasic isomerization of oct-1-en-3-ol for at least five times without a significant

  摘要水溶性[RuCl2（pta）（η6-p-cymene）]（pta = 1,3,5-triaza-7-phosphaadamantanetan）被用作催化剂，用于烯丙基醇（如oct-1-） en-3-ol在水性介质中。仅在pH> 10的缓冲溶液中或在碱金属碳酸盐存在下，辛烯-1-烯-3-醇异构化为辛烷-3-酮。“原位”催化剂（[RuCl2（pta）（η6-p-cymene）] + 2当量Na2CO3）的水溶液可再用于oct-1-en-3-ol的双相异构化至少五次不会明显降低催化活性。已经证明，碳酸盐不仅是该反应中的碱，而且导致形成高活性催化剂[Ru（η2-O2CO）（pta）（η6-p-cymene）]。分离出该化合物，为结晶固体，并进行了详细表征（包括X射线衍射）。
• A new amido-phosphine of dichloroacetic acid as an active ligand for metals of pharmaceutical interest. Synthesis, characterization and tests of antiproliferative and pro-apoptotic activity
  作者：Lorenza Marvelli、Valeria Ferretti、Valerio Bertolasi、Ilaria Lampronti、Roberto Gambari、Claudio Trapella、Giulia Turrin、Francesca Bonotto、Antonio Moriello、Paola Bergamini

  DOI：10.1016/j.jinorgbio.2019.110787

  日期：2019.10

  solution was dependent on the solvent, while the X-ray crystal structure of DCP showed an opposite orientation of the two amidic carbonyl groups (anti rotamer). The lipophilic, air and thermally stable DCP was found able to act regiospecifically as a P-donor ligand toward soft metal ions. By ligand substitution on appropriate precursors, we obtained the complexes 1–9, where proapoptotic DCA is associated

  我们在此描述了新的酰胺基次膦配体3,7-双（二氯乙酰基）-1,3,7-三氮杂-5-磷酸双环[3.3.1]壬烷（DCP）的合成和表征，DCP是二氯乙酸的衍生物（ DCA），其逆转癌细胞中抑制的线粒体凋亡的能力是已知的。在适当的条件下，通过发生P 2（1,3,5-三氮杂-7-磷金刚烷）的双N酰化反应，获得了DCP，同时损失了CH 2 。由于绕酰胺CN键的旋转受阻，观察到了三种旋转异构形式的DCP，其在溶液中的比例取决于溶剂，而DCP的X射线晶体结构显示两个酰胺羰基的方向相反（反旋转木马）。发现亲脂的，空气和热稳定的DCP能够对软金属离子以区域特异性的方式作为P-给体配体起作用。通过在适当的前体上进行配体取代，我们得到了配合物1 – 9，其中促凋亡DCA与已知对癌细胞具有细胞毒活性的金属离子（Pt 2 +，Pd 2 +，Ru 2 +，Re +，Au +）相关。与顺铂相比，在体外测试了DCP及其复
• Synthesis, characterisation and cytotoxicity studies of ruthenium arene complexes bearing trichlorogermyl ligands
  作者：Connor Deacon-Price、Dario Romano、Tina Riedel、Paul J. Dyson、Burgert Blom

  DOI：10.1016/j.ica.2018.09.019

  日期：2019.1

  sandwich ruthenium(II) trichlorogermyl complexes of the type [(η6-Arene)Ru(PR3)Cl(GeCl3)] (PR3 = Phosphane and phosphite ligands; Arene = p-cymene or C6H5-OC2H4OH) is reported: [(η6-p-cymene)Ru(P(OMe)3)Cl(GeCl3)] (1), [(η6-p-cymene)Ru(P(OPh)3)Cl(GeCl3)] (2), [(η6-p-cymene)Ru(PPh3)Cl(GeCl3)] (3), [(η6-p-cymene)Ru(pta)Cl(GeCl3)] (pta = 1,3,5-triaza-7-phosphaadamantane) (4) and [(η6-C6H5-OC2H4OH)Ru(pta)Cl(GeCl3)]

  摘要合成了五种[[η6-Arene] Ru（PR3）Cl（GeCl3）]（PR3 =磷和亚磷酸酯配体； Arene =对异丙基或C6H5-OC2H4OH）的半三明治钌（II）三氯锗烷基配合物。报告：[（η6-对-cymene）Ru（P（OMe）3）Cl（GeCl3）]（1），[（η6-对-cymene）Ru（P（OPh）3）Cl（GeCl3）]（2 ），[（η6-对-cymene）Ru（PPh3）Cl（GeCl3）]（3），[（η6-对-cymene）Ru（pta）Cl（GeCl3）]（pta = 1,3,5-triaza -7-磷金刚烷）（4）和[（η6-C6H5-OC2H4OH）Ru（pta）Cl（GeCl3）]（5）。η6-芳烃和膦配体的性质发生了变化，并且通过将GeCl2（来自GeCl2。（二恶烷））轻松插入各自易于接近的前体络合物[（η6-Arene）的Ru-Cl键中来制备配合物
• Binding of Organometallic Ruthenium(II) and Osmium(II) Complexes to an Oligonucleotide:  A Combined Mass Spectrometric and Theoretical Study
  作者：Antoine Dorcier、Paul J. Dyson、Christian Gossens、Ursula Rothlisberger、Rosario Scopelliti、Ivano Tavernelli

  DOI：10.1021/om049022a

  日期：2005.4.1

  A series of ruthenium(II) and osmium(II) p-cymene dichloride complexes with either a pta (1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane) or [pta-Me]Cl ligand which exhibit anticancer activity have been prepared and characterized by 1H and 31P NMR spectroscopy and mass spectrometry. Three of the complexes, viz. [Os(η6-p-cymene)Cl2(pta)] and [M(η6-p-cymene)Cl2(pta-Me)]Cl (M = Ru, Os), have also been

  一系列具有pta（1,3,5-triaza-7-phosphatritricyclo [3.3.1.1] decane）或[pta-Me] Cl配体的对氯苯甲基二氯化钌（II）和cy （II）配合物已经制备了抗癌活性并通过1 H和31 P NMR光谱和质谱进行了表征。三种配合物，即。[OS（η 6 - p -cymene）氯2（PTA）]和[M（η 6 - p -cymene）氯2（PTA-ME）]氯（M =钌，锇），也被其特征在于，单-晶体X射线衍射。pta复合物是选择性抗癌药，而pta-Me +这些复合物是不加区别的，会损害癌细胞和健康细胞，但代表了与药物活性有关的质子化的pta加合物的模型。为了建立它们的生物学活性和它们对DNA的影响（可能的体内靶标）之间的联系，使用电喷雾电离质谱研究了复合物对14-mer寡核苷酸（5'-ATACATGGTACATA-3'）的反应性。发现复合物与寡核
• Synthesis and characterisation of some water soluble ruthenium(II)–arene complexes and an investigation of their antibiotic and antiviral properties
  作者：Claire S Allardyce、Paul J Dyson、David J Ellis、Paul A Salter、Rosario Scopelliti

  DOI：10.1016/s0022-328x(02)01926-5

  日期：2003.2

  The water soluble ruthenium-p-cymene complexes [Ru(η6-p-cymene)X2]2 (X=Cl, Br, I or NCS), [Ru(η6-p-cymene)X2(pta)] (X=Cl, Br, I, or NCS; pta=1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane) and the tetraruthenium cluster [H4Ru4(η6-p-benzene)4]2+ have been prepared and their antimicrobial properties evaluated. They have been screened for antibacterial activity against Eschericia coli, Bascillus subtilis

  水溶性钌p -cymene络合物的[Ru（η 6 - p -cymene）X 2 ] 2（X =氯，Br，I或NCS），的[Ru（η 6 - p -cymene）X 2（PTA） ]（X =氯，溴，I，或NCS; PTA = 1,3,5-三氮杂-7-磷杂[3.3.1.1]癸烷）和tetraruthenium簇[H 4的Ru 4（η 6 - p -苯）已制备4 ] 2+并评估了其抗菌性能。已对它们进行了针对大肠埃希氏菌，枯草芽孢杆菌，铜绿假单胞菌，用于抵抗白色念珠菌，树脂枝孢菌和毛癣菌的抗真菌活性，以及对单纯疱疹病毒和脊髓灰质炎病毒的抗病毒活性。这些化合物的抗微生物活性似乎与DNA结合无关，但这可能是由于与蛋白质的特异性相互作用所致。的二聚体复合物的[Ru（η的固态结构6 - p氯-cymene）2 ] 2，在有机金属化学的重要前体复合物，也有报道。