TY - JOUR
T1 - Heterobimetallic Ru(μ-dppm)Fe and homobimetallic Ru(μ-dppm)Ru complexes as potential anti-cancer agents
AU - Herry, Brian
AU - Batchelor, Lucinda K.
AU - Roufosse, Basile
AU - Romano, Dario
AU - Baumgartner, Judith
AU - Borzova, Marina
AU - Reifenstahl, Tim
AU - Collins, Thomas
AU - Benamrane, Amal
AU - Weggelaar, Jordana
AU - Correia, Marie C.
AU - Dyson, Paul J.
AU - Blom, Burgert
N1 - Funding Information:
We would like to thank the Maastricht Science Programme (MSP) and Maastricht University (Faculty of Science and Engineering) for financial support of this research. BB thanks numerous students who did some preliminary work in this area as part of a research project within the MSP. JB thanks the Austrian Fonds zur Förderung der wissenschaftlichen Forschung (FWF) via the project P-30955. Dr. Maria Schlangen-Ahl (TU Berlin) is thanked for recording HRMS of all complexes.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/11/15
Y1 - 2019/11/15
N2 - Two heterobimetallic μ-dppm bridged Fe,Ru complexes, [(η6-Arene)RuCl2(μ-dppm)Fe(CO)I(η5-C5H5)] (Ar = C6H6 (1) and p-cymene (2), dppm = 1,1-bis(diphenylphosphino)methane) were obtained in a facile reaction between [Fe(η5-C5H5)I(CO)(κ1-dppm)] (5) and the corresponding [(η6-Arene)RuCl2]2 complexes by dimer cleavage, mediated by the pendant -PPh2 in 5. The homodinuclear Ru,Ru complex, [(η6-C6H6)RuCl2(μ-dppm)RuCl2(η6-C6H6)] (3), was also isolated in a straightforward fashion upon reaction of [(η6-C6H6)RuCl2(κ1-dppm)] (4) with [(η6-C6H6)RuCl2]2. All complexes were fully characterized by multinuclear (1H, 13C{1H}, 31P{1H}) NMR, UV–Vis, IR spectroscopy and HRMS (ESI), and additionally complex 3 was characterized by single crystal X-ray diffraction. Density functional theory (DFT) calculations (Level of theory B3LYP, basis set for H, C, P, O, N and Cl is 6-31 + G(d,p) and for Ru,Fe DGDZVP) of 1, 2 and 3 are also reported. Complexes 1 and 2 feature HOMOs and LUMOs delocalized over the iron-centered terminus of the bimetallic complexes. The cytotoxicity of 1–5 were evaluated on A2780 and A2780cisR (Human ovarian carcinoma) cell lines and the HEK293 (Human embryonic kidney) cell line. The complexes containing iron are more cytotoxic than cisplatin in the A2780 cells and significantly more active in the A2780cisR cell line and exhibit some selectivity towards the cancer cells. The dinuclear Ru,Ru complex 3 and the mononuclear complex 4 exhibit moderate activity on A2780 and A2780cisR cells also with some cancer cell selectivity. This study hence reveals the potential of Fe,Ru complexes as potent cytotoxic agents.
AB - Two heterobimetallic μ-dppm bridged Fe,Ru complexes, [(η6-Arene)RuCl2(μ-dppm)Fe(CO)I(η5-C5H5)] (Ar = C6H6 (1) and p-cymene (2), dppm = 1,1-bis(diphenylphosphino)methane) were obtained in a facile reaction between [Fe(η5-C5H5)I(CO)(κ1-dppm)] (5) and the corresponding [(η6-Arene)RuCl2]2 complexes by dimer cleavage, mediated by the pendant -PPh2 in 5. The homodinuclear Ru,Ru complex, [(η6-C6H6)RuCl2(μ-dppm)RuCl2(η6-C6H6)] (3), was also isolated in a straightforward fashion upon reaction of [(η6-C6H6)RuCl2(κ1-dppm)] (4) with [(η6-C6H6)RuCl2]2. All complexes were fully characterized by multinuclear (1H, 13C{1H}, 31P{1H}) NMR, UV–Vis, IR spectroscopy and HRMS (ESI), and additionally complex 3 was characterized by single crystal X-ray diffraction. Density functional theory (DFT) calculations (Level of theory B3LYP, basis set for H, C, P, O, N and Cl is 6-31 + G(d,p) and for Ru,Fe DGDZVP) of 1, 2 and 3 are also reported. Complexes 1 and 2 feature HOMOs and LUMOs delocalized over the iron-centered terminus of the bimetallic complexes. The cytotoxicity of 1–5 were evaluated on A2780 and A2780cisR (Human ovarian carcinoma) cell lines and the HEK293 (Human embryonic kidney) cell line. The complexes containing iron are more cytotoxic than cisplatin in the A2780 cells and significantly more active in the A2780cisR cell line and exhibit some selectivity towards the cancer cells. The dinuclear Ru,Ru complex 3 and the mononuclear complex 4 exhibit moderate activity on A2780 and A2780cisR cells also with some cancer cell selectivity. This study hence reveals the potential of Fe,Ru complexes as potent cytotoxic agents.
KW - Bioorganometallic chemistry
KW - Heterobimetallic complexes
KW - Homobimetallic complexes
KW - Metal-based drugs
KW - Cytotoxicity studies
KW - CONTAINING HETEROMETALLIC COMPLEXES
KW - TRANSITION-METAL-COMPLEXES
KW - CANCER STEM-CELLS
KW - RUTHENIUM COMPLEXES
KW - NAMI-A
KW - RUTHENIUM(II)-ARENE COMPOUND
KW - CYCLOPENTADIENYL COMPLEXES
KW - PHOSPHORUS LIGANDS
KW - PLATINUM COMPOUNDS
KW - CRYSTAL-STRUCTURE
U2 - 10.1016/j.jorganchem.2019.120934
DO - 10.1016/j.jorganchem.2019.120934
M3 - Article
SN - 0022-328X
VL - 901
JO - Journal of Organometallic Chemistry
JF - Journal of Organometallic Chemistry
M1 - 120934
ER -