Polydimethylsilylenes bearing pyrenyl groups exhibit emissions fromtwisted intramolecular charge transfer state between the aromatic ring and thesilicon backbone both in polar and nonpolar solvents.
Four cyclometalated complexes,namely[IrCl(η₅-pentamethylcyclopendadienyl)(κ₂C-diphenyl(1-pyrenyl)phosphane)](1)and[RhCl(η₅-pentamethylcyclopendadienyl)(κ₂C-diphenyl(1-pyrenyl)phosphane)](2),and their DMSO-coordina...Four cyclometalated complexes,namely[IrCl(η₅-pentamethylcyclopendadienyl)(κ₂C-diphenyl(1-pyrenyl)phosphane)](1)and[RhCl(η₅-pentamethylcyclopendadienyl)(κ₂C-diphenyl(1-pyrenyl)phosphane)](2),and their DMSO-coordinated counterparts[Ir(η₅-pentamethylcyclopendadienyl)(κS-dmso)(κ₂C-diphenyl(1-pyrenyl)phosphane)]PF₆(1·DMSO)and[Rh(η₅-pentamethylcyclopendadienyl)(κS-dmso)(κ₂C-diphenyl(1-pyrenyl)phosphane)]PF₆(2·DMSO),were synthesized and fully characterized,including their single-crystal X-ray structures.DNA-interacting 1 and 2 exhibits IC₅₀values in the range 0.53–0.79µM against bulk breast cancer cells and breast cancer stem cells(CSCs),i.e.,HMLER and HMLER-shEcad cells.The complexes are up to seven times more active than salinomycin and up to nine times more active than cisplatin.Moreover,1 and 2 are very effective(in the micromolar range)against mammospheres obtained from single cell suspensions of HMLER-shEcad cells,1 being thrice more toxic than 2 and up to 4.5-fold more potent than cisplatin and salinomycin.In depth mechanistic studies revealed that 1 induces necrosis,which is potentially dependent on necrosome formation and independent of ROS concentration.The efficacy of 1 against breast CSCs can be enhanced by co-treatment with PARP-1 inhibitors.展开更多
文摘Polydimethylsilylenes bearing pyrenyl groups exhibit emissions fromtwisted intramolecular charge transfer state between the aromatic ring and thesilicon backbone both in polar and nonpolar solvents.
基金support from the Agència de Gestiódels Ajuts Univeristaris i de Recerca(project 2021-SGR-01107)Spanish Ministerio de Ciencia,Innovación y Universidades(projects PID2020-115537RB-I00,PID2020-115658GB-I00 and PCI2021-122027-2B,MCIU/AEI/10.13039/501100011033 and European Union NextGenerationEU/PRTR)+2 种基金the RSC(RSC Research Fund grant RF19-7147)is kindly acknowledged.P.G.thanks the Catalan Institution for Research and Advanced Studies(ICREA)supported by an EPSRC New Investigator Award(EP/S005544/1)the University of Leicester.We also thank the Advanced Imaging Facility(RRID:SCR_020967)at the University of Leicester for support.
文摘Four cyclometalated complexes,namely[IrCl(η₅-pentamethylcyclopendadienyl)(κ₂C-diphenyl(1-pyrenyl)phosphane)](1)and[RhCl(η₅-pentamethylcyclopendadienyl)(κ₂C-diphenyl(1-pyrenyl)phosphane)](2),and their DMSO-coordinated counterparts[Ir(η₅-pentamethylcyclopendadienyl)(κS-dmso)(κ₂C-diphenyl(1-pyrenyl)phosphane)]PF₆(1·DMSO)and[Rh(η₅-pentamethylcyclopendadienyl)(κS-dmso)(κ₂C-diphenyl(1-pyrenyl)phosphane)]PF₆(2·DMSO),were synthesized and fully characterized,including their single-crystal X-ray structures.DNA-interacting 1 and 2 exhibits IC₅₀values in the range 0.53–0.79µM against bulk breast cancer cells and breast cancer stem cells(CSCs),i.e.,HMLER and HMLER-shEcad cells.The complexes are up to seven times more active than salinomycin and up to nine times more active than cisplatin.Moreover,1 and 2 are very effective(in the micromolar range)against mammospheres obtained from single cell suspensions of HMLER-shEcad cells,1 being thrice more toxic than 2 and up to 4.5-fold more potent than cisplatin and salinomycin.In depth mechanistic studies revealed that 1 induces necrosis,which is potentially dependent on necrosome formation and independent of ROS concentration.The efficacy of 1 against breast CSCs can be enhanced by co-treatment with PARP-1 inhibitors.
