Heterobimetallic Ru(μ-dppm)Fe and homobimetallic Ru(μ-dppm)Ru complexes as potential anti-cancer agents

Brian Herry, Lucinda K. Batchelor, Basile Roufosse, Dario Romano, Judith Baumgartner, Marina Borzova, Tim Reifenstahl, Thomas Collins, Amal Benamrane, Jordana Weggelaar, Marie C. Correia, Paul J. Dyson, Burgert Blom*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Article number120934
Number of pages9
JournalJournal of Organometallic Chemistry
Volume901
DOIs
Publication statusPublished - 15 Nov 2019

Keywords

  • Bioorganometallic chemistry
  • Heterobimetallic complexes
  • Homobimetallic complexes
  • Metal-based drugs
  • Cytotoxicity studies
  • CONTAINING HETEROMETALLIC COMPLEXES
  • TRANSITION-METAL-COMPLEXES
  • CANCER STEM-CELLS
  • RUTHENIUM COMPLEXES
  • NAMI-A
  • RUTHENIUM(II)-ARENE COMPOUND
  • CYCLOPENTADIENYL COMPLEXES
  • PHOSPHORUS LIGANDS
  • PLATINUM COMPOUNDS
  • CRYSTAL-STRUCTURE

Cite this

Herry, Brian ; Batchelor, Lucinda K. ; Roufosse, Basile ; Romano, Dario ; Baumgartner, Judith ; Borzova, Marina ; Reifenstahl, Tim ; Collins, Thomas ; Benamrane, Amal ; Weggelaar, Jordana ; Correia, Marie C. ; Dyson, Paul J. ; Blom, Burgert. / Heterobimetallic Ru(μ-dppm)Fe and homobimetallic Ru(μ-dppm)Ru complexes as potential anti-cancer agents. In: Journal of Organometallic Chemistry. 2019 ; Vol. 901.
@article{e67500b91d284b2fa39f2dd6f780304e,
title = "Heterobimetallic Ru(μ-dppm)Fe and homobimetallic Ru(μ-dppm)Ru complexes as potential anti-cancer agents",
abstract = "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.",
keywords = "Bioorganometallic chemistry, Heterobimetallic complexes, Homobimetallic complexes, Metal-based drugs, Cytotoxicity studies, CONTAINING HETEROMETALLIC COMPLEXES, TRANSITION-METAL-COMPLEXES, CANCER STEM-CELLS, RUTHENIUM COMPLEXES, NAMI-A, RUTHENIUM(II)-ARENE COMPOUND, CYCLOPENTADIENYL COMPLEXES, PHOSPHORUS LIGANDS, PLATINUM COMPOUNDS, CRYSTAL-STRUCTURE",
author = "Brian Herry and Batchelor, {Lucinda K.} and Basile Roufosse and Dario Romano and Judith Baumgartner and Marina Borzova and Tim Reifenstahl and Thomas Collins and Amal Benamrane and Jordana Weggelaar and Correia, {Marie C.} and Dyson, {Paul J.} and Burgert Blom",
year = "2019",
month = "11",
day = "15",
doi = "10.1016/j.jorganchem.2019.120934",
language = "English",
volume = "901",
journal = "Journal of Organometallic Chemistry",
issn = "0022-328X",
publisher = "Excerpta Medica, Elsevier Science",

}

Heterobimetallic Ru(μ-dppm)Fe and homobimetallic Ru(μ-dppm)Ru complexes as potential anti-cancer agents. / Herry, Brian; Batchelor, Lucinda K.; Roufosse, Basile; Romano, Dario; Baumgartner, Judith; Borzova, Marina; Reifenstahl, Tim; Collins, Thomas; Benamrane, Amal; Weggelaar, Jordana; Correia, Marie C.; Dyson, Paul J.; Blom, Burgert.

In: Journal of Organometallic Chemistry, Vol. 901, 120934, 15.11.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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

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

VL - 901

JO - Journal of Organometallic Chemistry

JF - Journal of Organometallic Chemistry

SN - 0022-328X

M1 - 120934

ER -