title: The key role of coligands in novel ruthenium(II)-cyclopentadienyl bipyridine derivatives: Ranging from non-cytotoxic to highly cytotoxic compounds.
abstract: A new family of eight ruthenium(II)-cyclopentadienyl bipyridine derivatives, bearing nitrogen, sulfur, phosphorous and carbonyl sigma bonded coligands, has been synthesized. Compounds bearing nitrogen bonded coligands were found to be unstable in aqueous solution, while the others presented appropriate stabilities for the biologic assays and pursued for determination of IC50 values in ovarian (A2780) and breast (MCF7 and MDAMB231) human cancer cell lines. These studies were also carried out for the [5: HSA] and [6: HSA] adducts (HSA=human serum albumin) and a better performance was found for the first case. Spectroscopic, electrochemical studies by cyclic voltammetry and density functional theory calculations allowed us to get some understanding on the electronic flow directions within the molecules and to find a possible clue concerning the structural features of coligands that can activate bipyridyl ligands toward an increased cytotoxic effect. X-ray structure analysis of compound [Ru(η(5)-C5H5)(bipy)(PPh3)][PF6] (7; bipy=bipyridine) showed crystallization on C2/c space group with two enantiomers of the [Ru(η(5)-C5H5)(bipy)(PPh3)](+) cation complex in the racemic crystal packing.
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
authors.forename: Leonor
authors.initials: L
authors.lastname: Côrte-Real
authors.affiliation: Área Departamental de Engenharia Química, Instituto Superior de Engenharia de Lisboa, Rua Conselheiro Emídio Navarro 1, 1959-007 Lisboa, Portugal; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: M Paula
authors.initials: MP
authors.lastname: Robalo
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela, LRS, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Nogueira
authors.affiliation: Departamento de Química Fundamental, Universidade da Coruña, Campus de A. Zapateria, 15071 A Coruña, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Avecilla
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
authors.forename: Tiago J L
authors.initials: TJ
authors.lastname: Silva
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
authors.forename: Filipa C
authors.initials: FC
authors.lastname: Santos
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
authors.forename: A Isabel
authors.initials: AI
authors.lastname: Tomaz
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal. Electronic address: mhgarcia@fc.ul.pt.
authors.forename: M Helena
authors.initials: MH
authors.lastname: Garcia
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal. Electronic address: amvalente@fc.ul.pt.
authors.forename: Andreia
authors.initials: A
authors.lastname: Valente
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D055664:Electrochemical Techniques; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D012709:Serum Albumin; D015082:2,2'-Dipyridyl; D012428:Ruthenium; D014364:Tryptophan
keywords: Cyclic voltammetry; Cyclopentadienyl; Cytotoxicity; Electronic flow; Ruthenium(II)