title: Os2 -Os4 Switch Controls DNA Knotting and Anticancer Activity.
abstract: Dinuclear trihydroxido-bridged osmium-arene complexes are inert and biologically inactive, but we show here that linking dihydroxido-bridged Os(II) -arene fragments by a bridging di-imine to form a metallacycle framework results in strong antiproliferative activity towards cancer cells and distinctive knotting of DNA. The shortened spacer length reduces biological activity and stability in solution towards decomposition to biologically inactive dimers. Significant differences in behavior toward plasmid DNA condensation are correlated with biological activity.
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.|Laboratory of Molecular Biology, Center for Cancer Research, NCI, Building 37, Room 5011, Bethesda, MD, 20892-4264, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.|Departamento de Química Inorgánica, Facultade de Química, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
authors.forename: María J
authors.identifier: 0000-0002-6299-4325
authors.initials: MJ
authors.lastname: Romero
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.|CIC biomaGUNE, Paseo de Miramón 182, 20009, Donostia-San Sebastián, Spain.
authors.forename: Luca
authors.initials: L
authors.lastname: Salassa
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Xi
authors.identifier: 0000-0002-9221-6241
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Abraha
authors.initials: A
authors.lastname: Habtemariam
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Guy J
authors.initials: GJ
authors.lastname: Clarkson
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Prokes
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Rodger
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Costantini
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK. P.J.Sadler@warwick.ac.uk.
authors.forename: Peter J
authors.identifier: 0000-0001-9160-1941
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004273:DNA, Neoplasm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000073396:Metal-Organic Frameworks / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009992:Osmium / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D000073396:Metal-Organic Frameworks; D009992:Osmium
keywords: DNA; cancer; organometallic; osmium; supramolecular