Correction for‘Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent’by Matteo Fiaschi et al.,Inorg.Chem.Front.,2024,11,2841-2...Correction for‘Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent’by Matteo Fiaschi et al.,Inorg.Chem.Front.,2024,11,2841-2862,https://doi.org/10.1039/D4QI00096J.展开更多
We conducted a systematic study on the reactivity of[Ru_(2)Cp_(2)(CO)4](Cp=η^(5)-C_(5)H_(5))with isocyanides and the subsequent methylation reaction to produce[Ru_(2)Cp_(2)(CO)2(μ-CO){μ-CNMe(R)}]^(+)complexes as CF...We conducted a systematic study on the reactivity of[Ru_(2)Cp_(2)(CO)4](Cp=η^(5)-C_(5)H_(5))with isocyanides and the subsequent methylation reaction to produce[Ru_(2)Cp_(2)(CO)2(μ-CO){μ-CNMe(R)}]^(+)complexes as CF_(3)SO_(3)^(−)salts,[2a-h]^(+)[R=Me,cyclohexyl(Cy),2,6-C_(6)H_(3)Me_(2)(Xyl),1H-indol-5-yl,2-naphthyl,4-C_(6)H_(4)OMe,(S)-CHMe(Ph),CH_(2)Ph(Bn)].The resulting products,including five novel ones,underwent structural characterization by IR and multinuclear NMR spectroscopy,with five of them further confirmed via single crystal X-ray diffraction.Compounds[2a-e,h]CF_(3)SO_(3)exhibit appreciable water solubility,substantial amphiphilic character and out-standing stability in physiological-like solutions(negligible degradation after 72 hours in DMEM at 37℃).Representative complexes[2b]^(+)and[2c]^(+)were additionally characterized through cyclic voltammetry in CH_(2)Cl_(2)and in aqueous phosphate buffer solution.Compounds[2a-d]CF_(3)SO_(3)were assessed for in vitro cyto-toxicity against A2780,A2080R and MCF-7 human cancer cell lines,and[2a-c]CF_(3)SO_(3)revealed significant-to-moderate cytotoxicity,outperforming cisplatin in several cases.The most favourable IC_(50)values were observed for[2d]CF_(3)SO_(3),ranging from 3.7 to 13.0μM.Experiments on the noncancerous human cell line MRC-5 highlighted a reasonable selectivity for[2b-d]CF_(3)SO_(3),with the highest selectivity indexes(SI)calcu-lated as 10.1(ratio of IC_(50)on MRC-5/IC_(50)on A2780)and 8.5(ratio of IC_(50)on MRC-5/IC_(50)on A2780R)for[2d]CF_(3)SO_(3).Subsequently,[2d]CF_(3)SO_(3)was tested across a panel of HOS,A549,PANC1,CaCo2,PC3 and HeLa cancer cells,showing variable cytotoxicity with IC_(50)values in the range of 9.7 to 20.3μM.The cellular effects of[2d]^(+)on A2780 cells were investigated using flow cytometry assays,focusing on the cell cycle modification,time-resolved cellular uptake,intracellular ROS production,mitochondrial membrane depolarization,induction of cell death through apoptosis,activation of caspases 3/7 and induction of autophagy.Overall,the results suggest a diphasic mechanism of action for[2d]^(+),inducing metabolic stress and arresting proliferation in the first/fast phase,followed by the induction of apoptosis and autophagy in the second/slower phase.展开更多
文摘Correction for‘Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent’by Matteo Fiaschi et al.,Inorg.Chem.Front.,2024,11,2841-2862,https://doi.org/10.1039/D4QI00096J.
基金L.B.,T.F.and F.M.thank the University of Pisa(Fondi di Ateneo 2020 and PRA_2020_39)for financial supportJ.V.,T.M.and Z.T.acknowledge the financial support from the ERDF/ESF Project Nanotechnologies for Future(CZ.02.1.01/0.0/0.0/16_019/0000754)thank Ms Marta Rešováfor help with biological testing,Prof.MarekŠebela for assistance with MALDI-TOF MS experiments,and Dr Ondřej Vrobel for assist-ance with some of the mass spectrometry experiments。
文摘We conducted a systematic study on the reactivity of[Ru_(2)Cp_(2)(CO)4](Cp=η^(5)-C_(5)H_(5))with isocyanides and the subsequent methylation reaction to produce[Ru_(2)Cp_(2)(CO)2(μ-CO){μ-CNMe(R)}]^(+)complexes as CF_(3)SO_(3)^(−)salts,[2a-h]^(+)[R=Me,cyclohexyl(Cy),2,6-C_(6)H_(3)Me_(2)(Xyl),1H-indol-5-yl,2-naphthyl,4-C_(6)H_(4)OMe,(S)-CHMe(Ph),CH_(2)Ph(Bn)].The resulting products,including five novel ones,underwent structural characterization by IR and multinuclear NMR spectroscopy,with five of them further confirmed via single crystal X-ray diffraction.Compounds[2a-e,h]CF_(3)SO_(3)exhibit appreciable water solubility,substantial amphiphilic character and out-standing stability in physiological-like solutions(negligible degradation after 72 hours in DMEM at 37℃).Representative complexes[2b]^(+)and[2c]^(+)were additionally characterized through cyclic voltammetry in CH_(2)Cl_(2)and in aqueous phosphate buffer solution.Compounds[2a-d]CF_(3)SO_(3)were assessed for in vitro cyto-toxicity against A2780,A2080R and MCF-7 human cancer cell lines,and[2a-c]CF_(3)SO_(3)revealed significant-to-moderate cytotoxicity,outperforming cisplatin in several cases.The most favourable IC_(50)values were observed for[2d]CF_(3)SO_(3),ranging from 3.7 to 13.0μM.Experiments on the noncancerous human cell line MRC-5 highlighted a reasonable selectivity for[2b-d]CF_(3)SO_(3),with the highest selectivity indexes(SI)calcu-lated as 10.1(ratio of IC_(50)on MRC-5/IC_(50)on A2780)and 8.5(ratio of IC_(50)on MRC-5/IC_(50)on A2780R)for[2d]CF_(3)SO_(3).Subsequently,[2d]CF_(3)SO_(3)was tested across a panel of HOS,A549,PANC1,CaCo2,PC3 and HeLa cancer cells,showing variable cytotoxicity with IC_(50)values in the range of 9.7 to 20.3μM.The cellular effects of[2d]^(+)on A2780 cells were investigated using flow cytometry assays,focusing on the cell cycle modification,time-resolved cellular uptake,intracellular ROS production,mitochondrial membrane depolarization,induction of cell death through apoptosis,activation of caspases 3/7 and induction of autophagy.Overall,the results suggest a diphasic mechanism of action for[2d]^(+),inducing metabolic stress and arresting proliferation in the first/fast phase,followed by the induction of apoptosis and autophagy in the second/slower phase.
