Synthesis, characterization and biological evaluation of cationic organoruthenium(ii) fluorene complexes: influence of the nature of the counteranion. Issue 35 (21st August 2019)

• Record Type: Journal Article
• Authors: Haghdoost, Mohammad Mehdi; Golbaghi, Golara; Guard, Juliette; Sielanczyk, Sarah; Patten, Shunmoogum A.; Castonguay, Annie
• Is Part Of: Dalton transactions. Volume 48:Issue 35(2019)
• Page Start: 13396
• Page End: 13405
• Publication Date: 2019-08-21
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c9dt00143c
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : In this study, the in vitro antiproliferative activity and the in vivo toxicity of ruthenium arene complexes bearing fluorene bidentate ligands was assessed in human breast cancer cells and on the development of zebrafish embryos, respectively. Abstract : In this study, five ruthenium arene complexes with fluorene-bearing N, N-(1 ) and N, O-(2 ) donor Schiff base ligands were synthesized and fully characterized. Cationic ruthenium complexes3 [X], ([Ru(η 6 -C6 H6 )(Cl)(fluorene-NCH-pyridine)][X] (where X = BF4, PF6, BPh4 ), were obtained by reacting ligand1 with [Ru(η 6 -C6 H6 )Cl2 ]2 in the presence of NH4 X salts, whereas neutral complex4, Ru(η 6 -C6 H6 )(Cl)(fluorene-NCH-naphtholate), was isolated by reacting ligand2 with the same precursor. It was possible to obtain a cationic version of the latter, 5 [BF4 ], by reacting4 with AgBF4 in the presence of pyridine. All compounds were fully characterized by NMR and HR-ESI-MS whereas some of them were also analyzed by single crystal X-ray analysis. Their in vitro antiproliferative activity was also assessed in human breast cancer cell lines, notably MCF-7 and T47D. Complex4 and its cationic counterpart5 [BF4 ] were found to be the most cytotoxic compounds of the series (IC50 = 6.2–16.2 μM) and displayed higher antiproliferative activities than cisplatin in both cell lines. It was found that5 [BF4 ] undergoes a ligand exchange reaction and readily converts to4 in the presence of 0.1 M NaCl, explaining the similarity in their observed cytotoxicities. Whereas3 [BF4 ] and3 [PF6 ] were found inactive at the tested concentrations, 3 [BPh4 ] displayed a considerable cytotoxicity (IC50 = 16.7–27.8 μM). Notably, 3 [BPh4 ], 4 (and5 [BF4 ]) were active against T47D, a cisplatin resistant cell line. Interestingly, 4 (16.4 μM) was found to be less cytotoxic than3 [BPh4 ] and cisplatin (6.6 and 7.9 μM, respectively) in breast healthy cells (MCF-12A). However, in comparison to4 and cisplatin (at 10 μM), a lower in vivo toxicity was observed for complex3 [BPh4 ] on the development of zebrafish ( Danio rerio ) embryos.