Facile entry to germanate and stannate complexes [(η6-arene)RuCl(η2-dppm)]+[ECl3]- (E = Ge, Sn) as potent anti-cancer agents
Autor: | Supratim Biswas, Christoph Marschner, Dario Romano, Sharon Prince, Siyabonga Ngubane, Suparna Chakraborty, Burgert Blom, Niccolo Aldeghi |
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Přispěvatelé: | RS: FSE Biobased Materials, Biobased Materials, AMIBM, RS: FSE AMIBM, Sciences, RS: FSE Sciences, Maastricht Science Programme, RS: FSE MSP |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Ionic complexes
Stannate Electrospray ionization Halide chemistry.chemical_element 010402 general chemistry 01 natural sciences Biochemistry Medicinal chemistry PLATINUM COMPOUNDS Inorganic Chemistry ANTITUMOR chemistry.chemical_compound RUTHENIUM COMPLEXES CISPLATIN Ruthenium anti-cancer agents CANCER STEM-CELLS Materials Chemistry NAMI-A Germanate CYTOTOXICITY Physical and Theoretical Chemistry RUTHENIUM(II)-ARENE COMPOUND 010405 organic chemistry Chemistry Organic Chemistry CHEMOTHERAPY 0104 chemical sciences Ruthenium Germanate and stannate complexes METAL-COMPLEXES Selectivity Single crystal |
Zdroj: | Journal of Organometallic Chemistry, 916:121214. Excerpta Medica, Elsevier Science |
ISSN: | 0022-328X |
Popis: | A series of arene Ru(II) salt complexes of the type [(eta(6)-arene)RuCl(eta(2)-dppm)](+)[ECl3](-) (arene = C6H6, p-cymene, 1,3,5-Me3C6H3; E = Ge, Sn) bearing trichlorogermanate and trichlorostannate anions are reported. Starting from the known complexes: [(eta(6)-C6H6)RuCl2(eta(1)-dppm)] (1), [(eta(6)-p-cymene)RuCl2(eta(1)-dppm)] (3) and the novel complex [(eta(6)-1,3,5-Me3C6H3)RuCl2(eta(1)-dppm)] (7) (dppm = 1,1-bis(diphenylphosphino)methane), reactions with SnCl2 or GeCl2(dioxane) respectively afforded, by halide abstraction at the ruthenium(II) centres in 1, 3 or 7 the salts: [(eta(6)-C6H6)RuCl(eta(2)-dppm)](+) SnCl3- (2), [(eta(6)-p-cymene)RuCl(eta(2)-dppm)](+) SnCl3- (4), [(eta(6)-C6H6)RuCl(eta(2)-dppm)](+) GeCl3- (5), [(eta(6)-p-cymene) RuCl(eta(2)-dppm)](+) GeCl3- (6), [(eta(6)-1,3,5-Me3C6H3)RuCl(eta(2)-dppm)](+) SnCl3- (8) and [(eta(6)-1,3,5-Me3C6H3) RuCl(eta(2)-dppm)](+) GeCl3- (9). The trichlorostannate complexes 2, 4 and 8 are extremely rare examples of ruthenium complexes bearing the SnCl3- counter anion, and the complexes 5, 6 and 9 are the first examples of ruthenium trichlorogermanate complexes to be reported. All compounds were isolated in high yields as air stable materials and were spectroscopically characterized by multinuclear NMR: (H-1, P-31 {H-1}, C-13{H-1}), Infra-red (IR), UV-Vis, and high resolution electrospray ionization mass spectrometry (HR-ESI-MS), the latter both in (+) and (-) mode. Additionally, single crystal X-ray diffraction analyses of salts 4 and 6 are reported, revealing pseudotetrahedral Ru(II) centres with eta(6) bound p-cymene ligands and eta(2)-bound dppm ligands with statistical disorder on the ECl3- anions (E = Ge (6), Sn (4)). Density functional theory calculations (B3LYP with the basis set 6-31 + G(d,p) for H, C, P and Cl atoms; while for Ru, Ge, and Sn atoms DGDZVP basis set) are reported for salts 4 and 6 revealing localization of the LUMOs on the ruthenium-arene rings and some localization on the chloride atom. Finally, MTT in vitro cytotoxicity assays for the MCF-7 and MDA-MB-231 breast cancer cell lines are reported for all complexes and compared to cisplatin. All complexes show remarkable in vitro cytotoxic activity and most are considerably more cytotoxic than cisplatin in both breast cancer cell lines: IC50 values range from 2.25 mu M (compound 2) to 5.97 mu M (compound 9) (cisplatin = 5.74 mu M) in MCF-7 cells; 2.20 mu M (compound 2) to 6.39 mu M (compound 5) (cisplatin = 13.98 mu M) in MDA-MB-231. Moreover, when compared to nonmalignant breast epithelial cells (MCF12A), all complexes exhibit promising selectivity indices (SI) with compound 5 having the highest SI in MCF-7 cells at 4.8; and compound 6 at 3.65 in MDA-MB-231, with most of the other compounds also being considerably more selective than cisplatin on both celllines (SI = 2.26 on MCF-7 and 0.93 on MDA-MB-231). A clonogenic assay was conducted for salts 5 and 6 and the results reveal that both compounds inhibited long-term (14 days) survival in both breast cancer cell lines tested indicating these drugs are very promising candidates for pre-clinical studies. (C) 2020 The Authors. Published by Elsevier B.V. |
Databáze: | OpenAIRE |
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