TY - JOUR
T1 - Facile synthesis of heterobimetallic [FeII(µ-diphosphine)RuII] and homobimetallic [FeII(µ-diphosphine)FeII] complexes and their in vitro cytotoxic activity on cisplatin-resistant cancer cells
AU - BenYosef, Danya
AU - Romano, Dario
AU - Hadiji, Mouna
AU - Dyson, Paul J.
AU - Blom, Burgert
N1 - Funding Information:
We thank the Maastricht Science Programme (MSP) and Maastricht University (Faculty of Science and Engineering) for financial support of this research. We also thank Maarten Honing, Peilang Han and Darya Hadavi (M4I, FHML (Maastricht MultiModal Molecular Imaging; Faculty Health, Medicine & Life Sciences, Maastricht University) for measuring the HRMS of all the compounds. Dr. Christian Bahn (MSP) is also thanked for useful discussions on the stereochemistry of the complexes.
Funding Information:
We thank the Maastricht Science Programme (MSP) and Maastricht University (Faculty of Science and Engineering) for financial support of this research. We also thank Maarten Honing, Peilang Han and Darya Hadavi (M4I, FHML (Maastricht MultiModal Molecular Imaging; Faculty Health, Medicine & Life Sciences, Maastricht University) for measuring the HRMS of all the compounds. Dr. Christian Bahn (MSP) is also thanked for useful discussions on the stereochemistry of the complexes. Associated Content. The supporting information is available free of charge. Supporting Information is available containing the synthesis and characterisation of known complexes, Multinuclear NMR, IR (experimental and calculated) and ESI-MS spectra of the compounds reported here and Cartesian coordinates for the complexes studied by DFT methods.
Publisher Copyright:
© 2020 The Authors
PY - 2020/9/24
Y1 - 2020/9/24
N2 - A series of heterobimetallic [Fe,Ru] and homobimetallic [Fe,Fe] complexes, featuring µ -diphosphine bridges between the two metal centres, are reported along with their in vitro cytotoxicity activity on the A2780cisR cell-line. The known starting material [CpFe(CO)2(CH3)] (Cp = η5-C5H5) (1) was reacted with dppe (1,2-bis(diphenylphosphino)ethane) forming the known mononuclear κ1-dppe complex: [CpFe(CO)(COCH3)(κ1-dppe)] (2) and the known dinuclear complex: and [[CpFe(CO)(COCH3)]2(µ-dppe)] (3). Dimer cleavage reactions between complex 2 and two ruthenium arene complexes [(η6-p-cymene)RuCl2]2 and [(η6-benzene)RuCl2]2 formed two new heterobimetallic complexes: [CpFe(CO)(COCH3)(µ-dppe)Ru(η6-cymene)Cl2] (4) and [CpFe(CO)(COCH3)(µ-dppe)Ru(η6-C6H6)Cl2] (5). A homobimetallic system, [[CpFe(CO)(I)]2(µ-dppb)] (6) was obtained by the facile reaction between of [CpFe(CO)2I] and 1,4-bis(diphenylphosphino)butane (dppb). Complex 6 was methylated using MeLi to generate the more lipophilic complex [[CpFe(CO)(CH3)]2(µ-dppb)] (7). All of the complexes were fully characterized by spectroscopy (1H, 13C {1H}, 31P {1H} NMR; FTIR, UV–Vis), and high resolution mass spectrometry (HRMS). Density functional theory calculations (DFT) (Level of theory B3LYP, basis set for H, C, P, O, Cl is 6-31+G(d,p) and for Ru, Fe, I is DGDZVP) on complexes 5 and 6 are also reported. An excellent agreement between the DFT calculated infra-red (IR) spectra of the optimised geometries of 5 and 6 was found with the experimentally determined spectra. In vitro cytotoxicity studies of all complexes was carried out on A2780cisR (cisplatin resistant ovarian cancer cell-line) and compared to cisplatin as a positive control and RAPTA-C as a negative control. Although limited to only one cell-line, the results show that the heterobimetallic complexes 4 and 5 are the most cytotoxic (IC50 = 4.9 ± 0.4 µM and 6.5 ± 0.1 µM respectively), whilst the dinculear [Fe,Fe] complexes exhibit no, or very low cytotoxicity.
AB - A series of heterobimetallic [Fe,Ru] and homobimetallic [Fe,Fe] complexes, featuring µ -diphosphine bridges between the two metal centres, are reported along with their in vitro cytotoxicity activity on the A2780cisR cell-line. The known starting material [CpFe(CO)2(CH3)] (Cp = η5-C5H5) (1) was reacted with dppe (1,2-bis(diphenylphosphino)ethane) forming the known mononuclear κ1-dppe complex: [CpFe(CO)(COCH3)(κ1-dppe)] (2) and the known dinuclear complex: and [[CpFe(CO)(COCH3)]2(µ-dppe)] (3). Dimer cleavage reactions between complex 2 and two ruthenium arene complexes [(η6-p-cymene)RuCl2]2 and [(η6-benzene)RuCl2]2 formed two new heterobimetallic complexes: [CpFe(CO)(COCH3)(µ-dppe)Ru(η6-cymene)Cl2] (4) and [CpFe(CO)(COCH3)(µ-dppe)Ru(η6-C6H6)Cl2] (5). A homobimetallic system, [[CpFe(CO)(I)]2(µ-dppb)] (6) was obtained by the facile reaction between of [CpFe(CO)2I] and 1,4-bis(diphenylphosphino)butane (dppb). Complex 6 was methylated using MeLi to generate the more lipophilic complex [[CpFe(CO)(CH3)]2(µ-dppb)] (7). All of the complexes were fully characterized by spectroscopy (1H, 13C {1H}, 31P {1H} NMR; FTIR, UV–Vis), and high resolution mass spectrometry (HRMS). Density functional theory calculations (DFT) (Level of theory B3LYP, basis set for H, C, P, O, Cl is 6-31+G(d,p) and for Ru, Fe, I is DGDZVP) on complexes 5 and 6 are also reported. An excellent agreement between the DFT calculated infra-red (IR) spectra of the optimised geometries of 5 and 6 was found with the experimentally determined spectra. In vitro cytotoxicity studies of all complexes was carried out on A2780cisR (cisplatin resistant ovarian cancer cell-line) and compared to cisplatin as a positive control and RAPTA-C as a negative control. Although limited to only one cell-line, the results show that the heterobimetallic complexes 4 and 5 are the most cytotoxic (IC50 = 4.9 ± 0.4 µM and 6.5 ± 0.1 µM respectively), whilst the dinculear [Fe,Fe] complexes exhibit no, or very low cytotoxicity.
KW - DIIRON PROPANEDISELENOLATO COMPLEXES
KW - CONTAINING HETEROMETALLIC COMPLEXES
KW - METAL-COMPLEXES
KW - RUTHENIUM COMPLEXES
KW - CRYSTAL-STRUCTURE
KW - ELECTRON-TRANSFER
KW - ARENE COMPLEXES
KW - TUMOR CELLS
KW - IRON
KW - DNA
U2 - 10.1016/j.ica.2020.119731
DO - 10.1016/j.ica.2020.119731
M3 - Article
SN - 0020-1693
VL - 510
JO - Inorganica Chimica Acta
JF - Inorganica Chimica Acta
M1 - 119731
ER -