TY - JOUR
T1 - Synthesis and in vitro anticancer studies of arene ruthenium(II) and arene osmium(II) complexes bearing arsine and stibine co-ligands on breast cancer cell-lines
AU - Latis, Stefan
AU - Marschner, Christoph
AU - Baumgartner, Judith
AU - Prince, Sharon
AU - Biswas, Supratim
AU - Chakraborty, Suparna
AU - Garcia, Kimberly G.
AU - Heeren, Ron M.A.
AU - Van Nuffel, Sebastiaan
AU - Blom, Burgert
N1 - Funding Information:
We would like to acknowledge Prof. Dr. Maarten Honing (FHML, UM) and his group for the nominal ESI-MS measurements. We also thank Maastricht University, the Faculty of Science and Engineering (FSE) and the Maastricht Science Programme (MSP) for financial support. Prof. Prince gratefully acknowledges and thanks the University of Cape Town (UCT), the National Research Foundation (NRF) of South Africa (UID: 120815), the International Centre for Genetic Engineering and Biotechnology (ICGEB) and the South African Medical Research Council (SAMRC) under a Self-Initiated Research Grant for financial support. The views and opinions expressed are those of the author(s) and do not necessarily represent the official views of the SAMRC.
Funding Information:
We would like to acknowledge Prof. Dr. Maarten Honing (FHML, UM) and his group for the nominal ESI-MS measurements. We also thank Maastricht University, the Faculty of Science and Engineering (FSE) and the Maastricht Science Programme (MSP) for financial support. Prof. Prince gratefully acknowledges and thanks the University of Cape Town (UCT), the National Research Foundation (NRF) of South Africa (UID: 120815), the International Centre for Genetic Engineering and Biotechnology (ICGEB) and the South African Medical Research Council (SAMRC) under a Self-Initiated Research Grant for financial support. The views and opinions expressed are those of the author(s) and do not necessarily represent the official views of the SAMRC.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/11/15
Y1 - 2023/11/15
N2 - We report the synthesis and full characterisation of piano-stool triphenylstibine and triphenylarsine arene complexes of the type: [MCl2(?6-p-cymene)(EPh3)] (E = As, Sb) and [MCl(?6-arene)(EPh3)(SnCl3)] (M = Ru, Os; E = As, Sb; arene = benzene, p-cymene); Ph = C6H5) and their in vitro cytotoxic evaluation on two breast cancer cell lines: MCF-7, MDA-MB-231 and MCF-12A. The compounds were synthesized via a facile two-step reaction: first, the cleavage of the corresponding dimer [(MCl2(?6-arene))2] (M = Ru, Os; arene = benzene, p-cymene) by either: AsPh3 or:SbPh3 to yield the mononuclear dichloride complexes [MCl2(?6-arene)(EPh3)] (M = Ru, Os; E = As, Sb; arene = benzene, p-cymene) 2: (M = Os, E = Sb, arene = p-cymene), 3: (M = Os, E = As, arene = p-cymene); and the known complexes 6: (M = Ru, E = Sb, arene = p-cymene), 7: (M = Ru, E = As, arene = p-cymene), 8: (M = Ru, E = Sb, arene = benzene) and 9: (M = Ru, E = As, arene = benzene). Using these dichloride complexes as starting materials, SnCl2 was inserted into the M-Cl bond to form the chiral trichlorostannyl complexes [MCl(?6-arene)(EPh3)(SnCl3)] (M = Ru, Os; E = As, Sb; arene = benzene, p-cymene) 4: (M = Os, E = Sb, arene = p-cymene), 5: (M = Os, E = As, arene = p-cymene), 10: (M = Ru, E = Sb, arene = p-cymene), 11: (M = Ru, E = As, arene = p-cymene), 12: (M = Ru, E = Sb, arene = benzene), and 13: (M = Ru, E = As, arene = benzene) respectively. The complexes were characterized spectroscopically by means of 1H, 13C{1H} NMR, FTIR, MP, UV–Visible and ESI-MS. The single crystal X-ray diffraction analysis of complex 2 and 10 is also reported revealing the expected piano-stool geometry at the metal centre. The in vitro activity of the complexes on the MCF-7, MDA-MB-231 and the non-tumorigenic cell-line MCF-12A are reported and compared to cisplatin as a positive control. Several tin containing complexes (4, 5, 10 and 12) show remarkable activity and selectivity outperforming cisplatin on both cancer cell-lines with the ruthenium complexes being the most active overall in this series of compounds. One of the most active complexes, 10 was also subjected to ToF-SIMS and the results of this study are reported.
AB - We report the synthesis and full characterisation of piano-stool triphenylstibine and triphenylarsine arene complexes of the type: [MCl2(?6-p-cymene)(EPh3)] (E = As, Sb) and [MCl(?6-arene)(EPh3)(SnCl3)] (M = Ru, Os; E = As, Sb; arene = benzene, p-cymene); Ph = C6H5) and their in vitro cytotoxic evaluation on two breast cancer cell lines: MCF-7, MDA-MB-231 and MCF-12A. The compounds were synthesized via a facile two-step reaction: first, the cleavage of the corresponding dimer [(MCl2(?6-arene))2] (M = Ru, Os; arene = benzene, p-cymene) by either: AsPh3 or:SbPh3 to yield the mononuclear dichloride complexes [MCl2(?6-arene)(EPh3)] (M = Ru, Os; E = As, Sb; arene = benzene, p-cymene) 2: (M = Os, E = Sb, arene = p-cymene), 3: (M = Os, E = As, arene = p-cymene); and the known complexes 6: (M = Ru, E = Sb, arene = p-cymene), 7: (M = Ru, E = As, arene = p-cymene), 8: (M = Ru, E = Sb, arene = benzene) and 9: (M = Ru, E = As, arene = benzene). Using these dichloride complexes as starting materials, SnCl2 was inserted into the M-Cl bond to form the chiral trichlorostannyl complexes [MCl(?6-arene)(EPh3)(SnCl3)] (M = Ru, Os; E = As, Sb; arene = benzene, p-cymene) 4: (M = Os, E = Sb, arene = p-cymene), 5: (M = Os, E = As, arene = p-cymene), 10: (M = Ru, E = Sb, arene = p-cymene), 11: (M = Ru, E = As, arene = p-cymene), 12: (M = Ru, E = Sb, arene = benzene), and 13: (M = Ru, E = As, arene = benzene) respectively. The complexes were characterized spectroscopically by means of 1H, 13C{1H} NMR, FTIR, MP, UV–Visible and ESI-MS. The single crystal X-ray diffraction analysis of complex 2 and 10 is also reported revealing the expected piano-stool geometry at the metal centre. The in vitro activity of the complexes on the MCF-7, MDA-MB-231 and the non-tumorigenic cell-line MCF-12A are reported and compared to cisplatin as a positive control. Several tin containing complexes (4, 5, 10 and 12) show remarkable activity and selectivity outperforming cisplatin on both cancer cell-lines with the ruthenium complexes being the most active overall in this series of compounds. One of the most active complexes, 10 was also subjected to ToF-SIMS and the results of this study are reported.
KW - Arene complexes
KW - Breast cancer
KW - Half-sandwich complexes
KW - In vitro studies
KW - Osmium(II)
KW - Ruthenium(II)
U2 - 10.1016/j.jorganchem.2023.122891
DO - 10.1016/j.jorganchem.2023.122891
M3 - Article
SN - 0022-328X
VL - 1001
JO - Journal of Organometallic Chemistry
JF - Journal of Organometallic Chemistry
IS - 1
M1 - 122891
ER -