The Contrasting Chemistry and Cancer Cell Cytotoxicity of Bipyridine and Bipyridinediol Ruthenium(II) Arene Complexes

• DOI: 10.1021/ic801361m
• Publication Date: 2008-11-14T11:00:26Z
• Authors: Tijana Bugarcic; Abraha Habtemariam; Jana Stepankova; Pavla Heringova; Jana Kasparkova; Robert J. Deeth; Russell D. L. Joh...; Alessandro Presci...; Andrew Parkin; Simon Parsons; Viktor Brabec; Peter J. Sadler
• Keywords: Bipyridine; 2,2'-Bipyridine

The synthesis and characterization of ruthenium(II) arene complexes [(η6-arene)Ru(N,N)Cl]0/+, where N,N = 2,2′-bipyridine (bipy), 2,2′-bipyridine-3,3′-diol (bipy(OH)2) or deprotonated (bipy(OH)O) as N,N-chelating ligand, benzene (bz), indan (ind), biphenyl (bip), p-terphenyl (p-terp), tetrahydronaphthalene (thn), tetrahydroanthracene (tha) dihydroanthracene (dha), are reported, including the X-ray crystal structures [(η6-tha)Ru(bipy)Cl][PF6] (1), [(η6-tha)Ru(bipy(OH)O)Cl] (2) [(η6-ind)Ru(bipy(OH)2)Cl][PF6] (8). Complexes 1 2 exibit CH (arene)/π (bipy bipy(OH)O) interactions. In structure protonated complex 8, pyridine rings twisted (by 17.31°). aqueous solution (pH 2−10), only forms present. Hydrolysis was relatively fast in (t1/2 4−15 min, 310 K). When is biphenyl, initial aquation followed by partial loss. with tha, thn, dha, ind p-terp, bipyridinediol chelating ligands, exhibited significant cytotoxicity toward A2780 human ovarian A549 lung cancer cells. [(η6-bip)Ru(bipy(OH)O)Cl] (7) [(η6-bz)Ru(bipy(OH)O)Cl] (5) moderate cells, but were inactive These activity data can be contrasted those parent bipyridine (1) which both cell lines. DFT calculations suggested that hydroxylation methylation bipy ligand have little effect on charge Ru. active binds strongly to 9-ethyl-guanine (9-EtG). adduct [(η6-tha)Ru(bipy(OH)O)(9-EtG-N7)][PF6] shows intramolecular interactions these more stable than arene/9-EtG π−π However (8) [(η6-ind)Ru(bipy)Cl][PF6] (16) bind weakly DNA. DNA may therefore not major target for studied here.