304865-77-8Relevant academic research and scientific papers
Elusive free bisimino-N-heterocyclic carbene and its rearrangement by C-C coupling. Characterization of relevant iridium(I) and chromium(II) complexes
Liu, Ping,Wesolek, Marcel,Danopoulos, Andreas A.,Braunstein, Pierre
, p. 6286 - 6297 (2013)
The potentially pincer-type N-heterocyclic (NHC) precursor salt 1,3-bis((E)-1-((2,6-diisopropylphenyl)imino)ethyl)-1H-imidazol-3-ium chloride, 3(Cl-), was prepared by reaction of N-(2,6-diisopropylphenyl) acetimidoyl chloride (1) with N-(1-(1H-imidazol-1-yl)ethylidene)-2,6- diisopropylaniline (2). Attempts to crystallize 3(Cl-) at different temperatures afforded single crystals of 3(Cl-)·MeCN from MeCN and the mixed salt 4 from toluene, in which 2H+(Cl-) and 3(Cl-) have cocrystallized. Deprotonation of 3(Cl-) yielded 1,3-bis[1-(2,6-diisopropylphenylimino)ethyl]imidazol-2-ylidene (5), the first bis(imino)-N-heterocyclic free carbene, and a novel product, 6, resulting formally from the insertion of the carbene carbon atom of 5 into the C-H bond of the N=CHN moiety of 2 and formation of a new C-C bond. The structures and NMR spectra of 4 and 6 indicate that loss of one N-substituent from the bis(imino) NHC core by exocyclic imidazole N-C bond cleavage is relatively easy. Reaction of 5 with [Ir(μ-Cl)(cod)]2 in pentane afforded in good yield the mononuclear, 16e Ir(I) NHC complex, [IrCl(cod)(5)] (7). The reaction of 6 with [CrCl2(THF)2] led to the isolation of the paramagnetic complex trans-[CrCl2(6)2] (8), in which the coordination geometry at the chromium is slightly distorted square planar. This complex is the first structurally characterized Cr(II) imidazole complex. The compounds 3(Cl-), 4, 6, 7, and 8 were identified by X-ray diffraction methods.
Structure-activity relationships for highly potent half-sandwich organoiridium(III) anticancer complexes with C^N-chelated ligands
Yang, Yuliang,Guo, Lihua,Ge, Xingxing,Shi, Shaopeng,Gong, Yuteng,Xu, Zhishan,Zheng, Xiaofeng,Liu, Zhe
, p. 1 - 7 (2018/11/23)
We herein report the synthesis, characterization, catalytic ability in converting coenzyme NADH to NAD+ and anticancer activity of half-sandwich iridium(III) complexes, [(η5-Cpxbiph)Ir(C^N)Cl]PF6 ?, where Cpxbiph = tetramethyl(biphenyl)cyclopentadienyl, C^N = varying imine-N-heterocyclic carbene ligands. The molecular structure of [(η5-Cpxbiph)Ir(L6)Cl]PF6 (complex Ir6), exhibiting the familiar “piano-stool” geometry, has been authenticated by X-ray crystallography. The anticancer activities of these complexes can be governed via substituent effects of three tunable domains and the ligand substituted variants offer an effective chelate ligand set that distinguishes anticancer activity and catalytic ability. Notably, complex Ir6 displays the greatest cytotoxic activities (IC50 = 0.85 μM), whose anticancer activity is more approximately 25-fold higher than that of cisplatin. The initial cell death mechanistic insight displays that this group of iridium(III) complexes exerts anticancer effects via cell cycle arrest, apoptosis induction and loss of the mitochondrial membrane potential. In addition, the confocal microscopy imaging shows that the complex Ir6 can damage lysosome. Overall, preliminary structure–activity relationships study and understanding of the cell death mechanism perhaps provide a rational strategy for enhancing anticancer activity of this family of complexes.
Novel and Versatile Imine-N-Heterocyclic Carbene Half-Sandwich Iridium(III) Complexes as Lysosome-Targeted Anticancer Agents
Yang, Yuliang,Guo, Lihua,Tian, Zhenzhen,Gong, Yuteng,Zheng, Hongmei,Zhang, Shumiao,Xu, Zhishan,Ge, Xingxing,Liu, Zhe
, p. 11087 - 11098 (2018/09/14)
We, herein, report the synthesis, characterization, luminescence properties, anticancer, and antibacterial activities of a family of novel half-sandwich iridium(III) complexes of the general formula [(n5-Cpx)Ir(C^N)Cl]PF6- [Cpx = pentamethylcyclopentadienyl (Cp) or tetramethyl(biphenyl)-cyclopentadienyl (Cpxbiph)] bearing versatile imine-N-heterocyclic carbene ligands. In this complex framework, substituents on four positions could be modulated, which distinguishes this class of complex and provides a large amount of flexibility and opportunity to tune the cytotoxicity of complexes. The X-ray crystal structures of complexes 4 and 10 exhibit the expected "piano-stool" geometry. With the exception of 1, 2, and 11, each complex shows potent cytotoxicity, with IC50 (half-maximum inhibitory concentration) values ranging from 1.99 to 25.86 μM toward A549 human lung cancer cells. First, the effect of four positions bearing different substituents in the complex framework on the anticancer activity, that is, structure-activity relationship, was systematically studied. Complex 8 (IC50 = 1.99 μM) displays the highest anticancer activities, whose cytotoxicity is more than 10-fold higher than that of the clinical platinum drug cisplatin against A549 cancer cells. Second, their chemical reactivity including nucleobases binding, catalytic activity in converting coenzyme NADH to NAD+, reaction with glutathione (GSH), and bovine serum albumin (BSA) binding is investigated. No reaction with nucleobase is observed. However, these iridium(III) complexes bind rapidly to GSH and can catalyze oxidation of NADH to NAD+. In addition, they show moderate binding affinity to BSA and the fluorescence quenching of BSA by the iridium (III) complexes is due to the static quenching. Third, the mode of cell death was also explored through flow cytometry experiments, including cell cycle, apoptosis induction, reactive oxygen species (ROS) and mitochondrial membrane potential. It seems that cell cycle perturbation, apoptosis induction, increase of ROS level and loss of mitochondrial membrane potential together contribute to the anticancer potency of these complexes. Last, the use of confocal microscopy provides insights into the microscopic mechanism that the typical and most active complex 8 enters A549 lung cancer cells mainly through energy-dependent pathway and is located in lysosome. Furthermore, lysosome damage and nuclear morphology were detected by confocal microscopy. Nuclear condensation and apoptotic bodies may finally induce cells apoptosis. Interestingly, complex 8 also shows antibacterial activity against Gram-positive Staphylococcus aureus. This work may provide an alternative and effective strategy to smart design of potent organometallic half-sandwich iridium(III) anticancer drugs.
Imine-N-Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p-Cymene Anticancer Complexes: A Structure–Activity Relationship Study
Yang, Yuliang,Guo, Lihua,Tian, Zhenzhen,Liu, Xicheng,Gong, Yuteng,Zheng, Hongmei,Ge, Xingxing,Liu, Zhe
, p. 2923 - 2933 (2018/09/12)
A family of novel imine-N-heterocyclic carbene ruthenium(II) complexes of the general formula [(η6-p-cymene)Ru(C^N)Cl]PF6? (where C^N is an imine-N-heterocyclic carbene chelating ligand with varying substituents) have been prepared and characterized. In this imine-N-heterocyclic carbene chelating ligand framework, there are three potential sites that can be modified, which distinguishes this class of ligand and provides a body of flexibilities and opportunities to tune the cytotoxicity of these ruthenium(II) complexes. The influence of substituent effects of three tunable domains on the anticancer activity and catalytic ability in converting coenzyme NADH to NAD+ is investigated. This family of complexes displays an exceedingly distinct anticancer activity against A549 cancer cells, despite their close structural similarity. Complex 9 shows the highest anticancer activity in this series against A549 cancer cells (IC50=14.36 μm), with an approximately 1.5-fold better activity than the clinical platinum drug cisplatin (IC50=21.30 μm) in A549 cancer cells. Mechanistic studies reveal that complex 9 mediates cell death mainly through cell stress, including cell cycle arrest, inducing apoptosis, increasing intracellular reactive oxygen species (ROS) levels, and depolarization of the mitochondrial membrane potential (MMP). Furthermore, lysosomal damage is also detected by confocal microscopy.
Imino Carbene Compounds and Derivatives, and Catalyst Compositions Made Therefrom
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Page/Page column 44, (2012/11/07)
The present invention provides imino carbene compounds and their derivatives, catalyst compositions containing these compounds in combination with an activator, and polymerization processes using these catalyst compositions to polymerize one or more olefi
