title: Multinuclear cytotoxic metallodrugs: physicochemical characterization and biological properties of novel heteronuclear gold-titanium complexes.
abstract: An unprecedented series of titanocene-gold bi- and trimetallic complexes of the general formula [[(η(5)-C(5)H(5))(μ-η(5):κ(1)-C(5)H(4)(CH(2))(n)PPh(2))TiCl(2)](m)AuCl(x)](q+) (n = 0, 2, or 4; m = 1, x = 1, q = 0 or m = 2, x = 0, q = 1) have been prepared and characterized spectroscopically. The luminescence spectroscopy and photophysics of one of the compounds, [[(η(5)-C(5)H(5))(μ-η(5):κ(1)-C(5)H(4)PPh(2))TiCl(2)](2)Au]PF(6), have been investigated in 2MeTHF solution and in the solid state at 77 and 298 K. Evidence for interfragment interactions based on the comparison of electronic band positions and emission lifetimes, namely, triplet energy transfer (ET) from the Au- to the Ti-containing chromophores, is provided. The cytotoxicity of the complexes was evaluated on A2780 ovarian cancer cells and on their cisplatin-resistant cell line A2780cisR; the compounds showed activity in the low micromolar range that was markedly more active than the corresponding titanocene-phosphine precursors [(η(5)-C(5)H(5))(η(5)-C(5)H(4)(CH(2))(n)PPh(2))TiCl(2)], cisplatin, and, for some of them, the gold analogue [(PPh(3))AuCl]. In an attempt to draw preliminary structure-activity relationships, cell uptake measurements and interaction studies with plasmid DNA and the model protein ubiquitin (Ub) have been undertaken on some of the compounds.
authors.affiliation: Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 5260 CNRS-Université de Bourgogne, 9 avenue A. Savary, BP 47870, 21078 Dijon, France.
authors.forename: Margot
authors.initials: M
authors.lastname: Wenzel
authors.forename: Benoît
authors.initials: B
authors.lastname: Bertrand
authors.forename: Marie-Joëlle
authors.initials: MJ
authors.lastname: Eymin
authors.forename: Virginie
authors.initials: V
authors.lastname: Comte
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Harvey
authors.forename: Philippe
authors.initials: P
authors.lastname: Richard
authors.forename: Michael
authors.initials: M
authors.lastname: Groessl
authors.forename: Olivier
authors.initials: O
authors.lastname: Zava
authors.forename: Hedi
authors.initials: H
authors.lastname: Amrouche
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Harvey
authors.forename: Pierre
authors.initials: P
authors.lastname: Le Gendre
authors.forename: Michel
authors.initials: M
authors.lastname: Picquet
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D049449:Luminescence; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014025:Titanium / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C406884:titanocene; D006046:Gold; D014025:Titanium