Cytotoxic dimeric half‐sandwich Ru(II), Os(II) and Ir(III) complexes containing the 4, 4′‐biphenyl‐based bridging ligands. (20th May 2020)

• Record Type: Journal Article
• Authors: Štarha, Pavel; Hošek, Jan; Trávníček, Zdeněk; Dvořák, Zdeněk
• Is Part Of: Applied organometallic chemistry. Volume 34:Number 9(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-05-20
• Subjects: caspases -- cytotoxicity -- flow cytometry -- half‐sandwich -- iridium; Organometallic chemistry -- Periodicals; Organometallic compounds -- Periodicals; 547.05
• DOI: 10.1002/aoc.5785
• Languages: English
• ISSNs: 0268-2605

Abstract

Abstract : A series of dinuclear half‐sandwich Ru(II), Os(II) and Ir(III) complexes [Ru2 (μ‐L n )(η 6 ‐ p cym)2 Cl2 ](PF6 )2 (1, 4 ), [Os2 (μ‐L n )(η 6 ‐ p cym)2 Cl2 ](PF6 )2 (2, 5 ) and [Ir2 (μ‐L n )(η 5 ‐Cp*)2 Cl2 ](PF6 )2 (3, 6 ), based on 4, 4′‐biphenyl‐based bridging Schiff base ligands N, N′ ‐(biphenyl‐4, 4′‐diyldimethylidyne)bis‐2‐(pyridin‐2‐yl)methanamine (L 1 ; for 1 –3 ) and N, N′ ‐(biphenyl‐4, 4′‐diyldimethylidyne)bis‐2‐(pyridin‐2‐yl)ethanamine (L 2 ; for 4 –6 ) is reported; p cym = 1‐methyl‐4‐(propan‐2‐yl)benzene, Cp* = pentamethylcyclopentadienyl. The complexes were characterized by relevant analytical techniques (i.e. elemental analysis, FT‐IR, NMR, ESI‐MS), and their in vitro cytotoxicity was assessed at six cancerous and two non‐cancerous (healthy) human cell lines. Overall, complexes 4 –6, containing the L 2 bridging ligand, revealed higher cytotoxicity as compared with 1 –3 and, thus, they were studied in greater detail. The best‐performing complex 6 exceeded at least twice the in vitro cytotoxicity of cisplatin and showed high selectivity towards the cancer cells over the normal ones, including the primary culture of human hepatocytes. In contrast to cisplatin, complexes 4 –6 did not induce the cell cycle modification of the treated A2780 human ovarian carcinoma cells (studied by flow cytometry and Western blot analysis). High levels of superoxide anion were induced by complexes 4 –6 at the A2780 cells. The levels of activated forms of Caspase‐3 and Caspase‐8 at the A2780 cells treated by Ru(II) complex 4 were comparable with cisplatin, while complexes 5 and 6 had only a minor effect on activation of these caspases. Abstract : Dinuclear Ru (II), Os (II) and Ir (III) complexes were derived from two different 4, 4′‐biphenyl‐basedN‐donor ligands bridging two half‐sandwich chlorido moieties. Complexes were characterized by relevant techniques and studied for their in vitro cytotoxicity at various human cancer and healthy cell lines. Some of the reported complexes revealed higher in vitro cytotoxicity than cisplatin.