Bugarcic, Tijana, Habtemariam, Abraha, Stepankova, Jana, Heringova, Pavla, Kasparkova, Jana, Deeth, Robert J., Johnstone, Russell D. L., Prescimone, Alessandro, Parkin, Andrew, Parsons, S. (Simon), Brabec, V. (Viktor) and Sadler, P. J.. (2008) The contrasting chemistry and cancer cell cytotoxicity of bipyridine and bipyridinediol ruthenium(II) arene complexes. Inorganic Chemistry, Vol.47 (No.24). pp. 11470-11486. ISSN 0020-1669

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Abstract

The synthesis and characterization of ruthenium(II) arene complexes [(eta(6)-arene)Ru(N,N)Cl](0/+), where N,N = 2,2'-bipyridine (bipy), 2,2'-bipyridine-3,3'-diol (bipy(OH)(2)) or deprotonated 2,2'-bipyridine-3,3'-diol (bipy(OH)O) as N,N-chelating ligand, arene = benzene (bz), indan (ind), biphenyl (bip), rho-terphenyl (rho-terp), tetrahydronaphthalene (thn), tetrahydroanthracene (tha) or dihydroanthracene (dha), are reported, including the X-ray crystal structures of [(eta(6)-tha)Ru(bipy)Cl][PF6] (1), [(eta(6)-tha)Ru(bipy(OH)O)Cl] (2) and [(eta(6)-ind)Ru(bipy(OH)(2))Cl][PF6] (8). Complexes 1 and 2 exibit CH (arene)/pi (bipy or bipy(OH)O) interactions. In the X-ray structure of protonated complex 8, the pyridine rings are twisted (by 17.31 degrees). In aqueous solution (pH = 2-10), only deprotonated (bipy(OH)0) forms are present. Hydrolysis of the complexes was relatively fast in aqueous solution (t1/2 = 4-15 min, 310 K). When the arene is biphenyl, initial aquation of the complexes is followed by partial arene loss. Complexes with arene = tha, thn, dha, ind and rho-terp, and deprotonated bipyridinediol (bipy(OH)O) as chelating ligands, exhibited significant cytotoxicity toward A2780 human ovarian and A549 human lung cancer cells. Complexes [(eta(6)-bip)Ru(bipy(OH)O)Cl] (7) and [(eta(6)-bz)Ru(bipy(OH)O)Cl] (5) exhibited moderate cytotoxicity toward A2780 cells, but were inactive toward A549 cells. These activity data can be contrasted with those of the parent bipyridine complex [(eta(6)-tha)Ru(bipy)Cl][PF6] (1) which is inactive toward both A2780 ovarian and A549 lung cell lines. DFT calculations suggested that hydroxylation and methylation of the bipy ligand have little effect on the charge on Ru. The active complex [(eta(6)-tha)Ru(bipy(OH)O)Cl] (2) binds strongly to 9-ethyl-guanine (9-EtG). The X-ray crystal structure of the adduct [(eta(6)-tha)Ru(bipy(OH)O)(9-EtG-N7)][PF6] shows intramolecular CH (arene)/pi (bipy(OH)O) interactions and DFT calculations suggested that these are more stable than arene/9-EtG pi-pi interactions. However [(eta(6)-ind)Ru(bipy(OH)(2))Cl][PF6] (8) and [(eta(6-)ind)Ru(bipy)Cl][PF6] (16) bind only weakly to DNA. DNA may therefore not be the major target for complexes studied here.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	Cell-mediated cytotoxicity, Cancer cells, Aromatic compounds
Journal or Publication Title:	Inorganic Chemistry
Publisher:	American Chemical Society
ISSN:	0020-1669
Date:	15 December 2008
Volume:	Vol.47
Number:	No.24
Number of Pages:	17
Page Range:	pp. 11470-11486
Identification Number:	10.1021/ic801361m
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Czech Republic. Ministerstvo školství, mládeže a tělovýchovy [Czech Republic. Ministry of Education, Youth, and Sport], Akademie věd České republiky [Academy of Sciences of the Czech Republic] (ASCR), Ministerstvo zdravotnictví České republiky [Ministry of Health of the Czech Republic] (MZCR)
Grant number:	LC06030 (MSMT), 6198959216 (MSMT), ME08017 (MSMT), OC08003 (MSMT), 1QS500040581 (ASCR), KAN200200651 (ASCR), AV0Z50040507 (ASCR), AV0Z50040702 (ASCR), IAA400040803 (ASCR), NR8562-4/2005 (MZCR)
URI:	http://wrap.warwick.ac.uk/id/eprint/28921

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