Eight diiron_((I))bis-cyclopentadienyl complexes with a bridging methylthiocarbyne ligand were prepared from the tris-carbonyl precursor[Fe_(2)Cp_(2)(CO)_(2)(μ-CO)(μ-CSMe)]CF_(3)SO_(3)(Cp=η^(5)-C_(5)H_(5))through t...Eight diiron_((I))bis-cyclopentadienyl complexes with a bridging methylthiocarbyne ligand were prepared from the tris-carbonyl precursor[Fe_(2)Cp_(2)(CO)_(2)(μ-CO)(μ-CSMe)]CF_(3)SO_(3)(Cp=η^(5)-C_(5)H_(5))through the substitution of one or two terminal carbonyls with a variety of monodentate ligands including phosphanes/phosphite,alkyl/aryl isocyanides or iodide.All compounds were isolated in 57-84%yield and characterized by IR and multinuclear NMR spectroscopy and by X-ray diffraction in five representative cases.Their bonding,stereochemistry and isomerization processes were investigated by NMR and DFT techniques.The water solubility and octanol-water partition coefficient heavily depend on the different monodentate ligands.All cationic complexes displayed substantial inertness in aqueous and cell culture medium solutions at 37℃over 24-48 h.Their cytotoxicity was assessed on a panel of human cancer cell lines(HCT 116,MCF-7 and A2780).Four compounds showed IC_(50) values down to the nanomolar range in colorectal,breast and ovarian cancer cell lines.The most potent compound,[Fe_(2)Cp_(2)(CO)(PPh_(3))(μ-CO)(μ-CSMe)]CF_(3)SO_(3),revealed enhanced Fe accumulation and significant disruption of cell redox homeostasis in A2780 cells that resulted in caspase-independent apoptotic cell death.The six times higher sensitivity of A2780 cells in comparison to healthy fibroblasts(MRC-5)underlines the potential of this compound to preferably target cancer cells.Overall,the variation of monodentate ligands on a diiron_((I))bis-cyclopentadienylμ-thiocarbyne core represents a simple strategy to obtain robust compounds with tuneable physico-chemical properties and possibly also a remarkable anticancer activity.展开更多
Cationic triiron complexes resulting from the conjugation of the ferrocenyl skeleton(Fc)with a diiron bis-cyclopentadienyl core through a variable vinyliminium linker,[Fe2Cp2(CO)(μ-CO){μ–η^(1):η^(3)-C(Fc)CHCN(R)(...Cationic triiron complexes resulting from the conjugation of the ferrocenyl skeleton(Fc)with a diiron bis-cyclopentadienyl core through a variable vinyliminium linker,[Fe2Cp2(CO)(μ-CO){μ–η^(1):η^(3)-C(Fc)CHCN(R)(R′)}]CF_(3)SO_(3)([2a–i]CF_(3)SO_(3),Cp=η^(5)-C5H5,R,R′=alkyl,aryl),were synthesised in 70–94%yield,and the homologous nitrate salt was also prepared in one case([2h]NO_(3)).The neutral derivatives[Fe2Cp2(CO)(μ-CO){μ–η^(1):η^(3)-C(Fc)CHC(CN)NMe2}],3,and[FeCp(CO){CN(Me)(Xyl)CHC(Fc)C([double bond,length as m-dash]O)}],4(Xyl=2,6-C6H3Me2),were obtained in ca.70%yield by reactions of the respective precursors[2h]CF_(3)SO_(3) and[2i]CF_(3)SO_(3) with NBu4CN and pyrrolidine,respectively.All products were purified by alumina chromatography and fully characterised by analytical and spectroscopic methods,and by single crystal X-ray diffraction in the cases of[2a]CF_(3)SO_(3) and 3.The cytotoxicity of the complexes was assessed on A2780,A2780cisR and BxPC-3 cancer cell lines,and the nontumoral Balb/3T3 clone A31.Most of the cationic complexes display IC50 values in the low micromolar/nanomolar range concerning the cancer cell lines,and up to 35 times higher values on the nontumoral cells.In order to shed light on the mode of action,selected complexes were further characterised by cyclic voltammetry and spectroelectrochemical experiments,and assessed for their potential to trigger ROS production and to interact with a range of biomolecules,i.e.a synthetic dodecapeptide as a simplified model for thioredoxin reductase(TrxR-pept),some model proteins(cytochrome c,hen egg-white lysozyme,ubiquitin,bovine serum albumin,superoxide dismutase and human carbonic anhydrase)and one single-stranded oligonucleotide(ODN2).展开更多
The development of efficient electrocatalysts for proton reduction(H_(2)production)based on earth-abundant metals is a scientific challenge with implications for energy storage and generation.Inspired by[FeFe]-hydroge...The development of efficient electrocatalysts for proton reduction(H_(2)production)based on earth-abundant metals is a scientific challenge with implications for energy storage and generation.Inspired by[FeFe]-hydrogenase enzymes,several compounds based on the{Fe_(2)Cp_(2)(CO)_(2)}framework have been investigated in this respect but,to date,only two charge-neutral derivatives,with a terminal cyanide and a bridging dimethylamino-(CNMe_(2)^(+))or methylthio-(CSMe^(+))carbyne ligand,were found to be effective electrocatalysts.Herein,we extended the investigation to related cationic derivatives with the cyanide ligand being replaced with various monodentate,hydrophilic N-P-or S-donor ligands.Aminocarbyne complexes[Fe_(2)Cp_(2)(CO)(L)(μ-CO)(μ-CNMe_(2))]^(+)(L=NH3,[2a]^(+);imidazole,[2b]^(+);pyrazole,[2c]^(+);thiourea,[2d]^(+);1,3,5-triaza-7-phosphadamantane,PTA,[2e]^(+))and thiocarbyne complexes[Fe_(2)Cp_(2)(CO)(L)(μ-CO)(μ-CSMe)]^(+)(L=imidazole,[4b]^(+);PTA,[4e]^(+);4-dimethylaminopyridine,DMAP,[4f]^(+);MeCN[4g]^(+)),five of which are unprecedented,were prepared,isolated as triflate salts and characterized by IR and NMR spectroscopy and X-ray diffraction in two cases.These nine diiron compounds were screened by cyclic voltammetry for their redox chemistry in acetonitrile and the electrocatalytic activity in the H_(2)evolution reaction from acetic acid.Two thiocarbyne complexes,featuring imidazole([4b]^(+))and DMAP([4f]^(+))as monodentate ligands emerged for their remarkable electrocatalytic activity,outperforming the previously-investigated cyanide derivatives.A mechanism for the electrocatalytic cycle is proposed based on combined electrochemical,spectroscopic and literature data.展开更多
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
基金support from the University of Pisa under the“PRA 2022-2023-Progetti di Ricerca di Ateneo”(Institutional Research Grants)-Project no.PRA_2022_12“New challenges of transition metal and lanthanide complexes in the perspective of green chemistry”the Ministry of Science,Technological Development,and Innovation of the Republic of Serbia(No.451-03-136/2025-03/200007)for the financial support.
文摘Eight diiron_((I))bis-cyclopentadienyl complexes with a bridging methylthiocarbyne ligand were prepared from the tris-carbonyl precursor[Fe_(2)Cp_(2)(CO)_(2)(μ-CO)(μ-CSMe)]CF_(3)SO_(3)(Cp=η^(5)-C_(5)H_(5))through the substitution of one or two terminal carbonyls with a variety of monodentate ligands including phosphanes/phosphite,alkyl/aryl isocyanides or iodide.All compounds were isolated in 57-84%yield and characterized by IR and multinuclear NMR spectroscopy and by X-ray diffraction in five representative cases.Their bonding,stereochemistry and isomerization processes were investigated by NMR and DFT techniques.The water solubility and octanol-water partition coefficient heavily depend on the different monodentate ligands.All cationic complexes displayed substantial inertness in aqueous and cell culture medium solutions at 37℃over 24-48 h.Their cytotoxicity was assessed on a panel of human cancer cell lines(HCT 116,MCF-7 and A2780).Four compounds showed IC_(50) values down to the nanomolar range in colorectal,breast and ovarian cancer cell lines.The most potent compound,[Fe_(2)Cp_(2)(CO)(PPh_(3))(μ-CO)(μ-CSMe)]CF_(3)SO_(3),revealed enhanced Fe accumulation and significant disruption of cell redox homeostasis in A2780 cells that resulted in caspase-independent apoptotic cell death.The six times higher sensitivity of A2780 cells in comparison to healthy fibroblasts(MRC-5)underlines the potential of this compound to preferably target cancer cells.Overall,the variation of monodentate ligands on a diiron_((I))bis-cyclopentadienylμ-thiocarbyne core represents a simple strategy to obtain robust compounds with tuneable physico-chemical properties and possibly also a remarkable anticancer activity.
基金the University of Pisa for financial support(PRA_2020_39).
文摘Cationic triiron complexes resulting from the conjugation of the ferrocenyl skeleton(Fc)with a diiron bis-cyclopentadienyl core through a variable vinyliminium linker,[Fe2Cp2(CO)(μ-CO){μ–η^(1):η^(3)-C(Fc)CHCN(R)(R′)}]CF_(3)SO_(3)([2a–i]CF_(3)SO_(3),Cp=η^(5)-C5H5,R,R′=alkyl,aryl),were synthesised in 70–94%yield,and the homologous nitrate salt was also prepared in one case([2h]NO_(3)).The neutral derivatives[Fe2Cp2(CO)(μ-CO){μ–η^(1):η^(3)-C(Fc)CHC(CN)NMe2}],3,and[FeCp(CO){CN(Me)(Xyl)CHC(Fc)C([double bond,length as m-dash]O)}],4(Xyl=2,6-C6H3Me2),were obtained in ca.70%yield by reactions of the respective precursors[2h]CF_(3)SO_(3) and[2i]CF_(3)SO_(3) with NBu4CN and pyrrolidine,respectively.All products were purified by alumina chromatography and fully characterised by analytical and spectroscopic methods,and by single crystal X-ray diffraction in the cases of[2a]CF_(3)SO_(3) and 3.The cytotoxicity of the complexes was assessed on A2780,A2780cisR and BxPC-3 cancer cell lines,and the nontumoral Balb/3T3 clone A31.Most of the cationic complexes display IC50 values in the low micromolar/nanomolar range concerning the cancer cell lines,and up to 35 times higher values on the nontumoral cells.In order to shed light on the mode of action,selected complexes were further characterised by cyclic voltammetry and spectroelectrochemical experiments,and assessed for their potential to trigger ROS production and to interact with a range of biomolecules,i.e.a synthetic dodecapeptide as a simplified model for thioredoxin reductase(TrxR-pept),some model proteins(cytochrome c,hen egg-white lysozyme,ubiquitin,bovine serum albumin,superoxide dismutase and human carbonic anhydrase)and one single-stranded oligonucleotide(ODN2).
基金the University of Pisa(Fondi di Ateneo 2020 and PRA_2020_39)for financial supportthe research project PNRR ECO-spoke 2-ECOSYSTER J33C22001240001.
文摘The development of efficient electrocatalysts for proton reduction(H_(2)production)based on earth-abundant metals is a scientific challenge with implications for energy storage and generation.Inspired by[FeFe]-hydrogenase enzymes,several compounds based on the{Fe_(2)Cp_(2)(CO)_(2)}framework have been investigated in this respect but,to date,only two charge-neutral derivatives,with a terminal cyanide and a bridging dimethylamino-(CNMe_(2)^(+))or methylthio-(CSMe^(+))carbyne ligand,were found to be effective electrocatalysts.Herein,we extended the investigation to related cationic derivatives with the cyanide ligand being replaced with various monodentate,hydrophilic N-P-or S-donor ligands.Aminocarbyne complexes[Fe_(2)Cp_(2)(CO)(L)(μ-CO)(μ-CNMe_(2))]^(+)(L=NH3,[2a]^(+);imidazole,[2b]^(+);pyrazole,[2c]^(+);thiourea,[2d]^(+);1,3,5-triaza-7-phosphadamantane,PTA,[2e]^(+))and thiocarbyne complexes[Fe_(2)Cp_(2)(CO)(L)(μ-CO)(μ-CSMe)]^(+)(L=imidazole,[4b]^(+);PTA,[4e]^(+);4-dimethylaminopyridine,DMAP,[4f]^(+);MeCN[4g]^(+)),five of which are unprecedented,were prepared,isolated as triflate salts and characterized by IR and NMR spectroscopy and X-ray diffraction in two cases.These nine diiron compounds were screened by cyclic voltammetry for their redox chemistry in acetonitrile and the electrocatalytic activity in the H_(2)evolution reaction from acetic acid.Two thiocarbyne complexes,featuring imidazole([4b]^(+))and DMAP([4f]^(+))as monodentate ligands emerged for their remarkable electrocatalytic activity,outperforming the previously-investigated cyanide derivatives.A mechanism for the electrocatalytic cycle is proposed based on combined electrochemical,spectroscopic and literature data.
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.
