title: Selective, cytotoxic organoruthenium(II) full-sandwich complexes: a structural, computational and in vitro biological study.
abstract: A structurally diverse range of lipophilic, cationic η(6)-arene η(5)-cyclopentadienyl (η(5)-Cp*) full-sandwich complexes of ruthenium(II) have been prepared and structurally characterized by Fourier-transform IR and NMR spectroscopy, electrospray mass spectrometry, and elemental microanalyses. Computational experiments incorporating the Hartree-Fock theory and the second-order Møller-Plesset perturbation theory predict each complex to possess a uniform δ+ electrostatic potential, with the cationic charge of the [RuCp*](+) moiety completely delocalizing throughout the molecular structure of each metallocene. In vitro cytotoxicity studies demonstrate these delocalized lipophilic cations to be potent growth inhibitors of eleven unique tumorigenic cell lines, while exhibiting significantly lower levels of toxicity towards both a normal human fibroblast and a mouse macrophage cell line. Single-crystal X-ray structural determinations are additionally reported for five complexes, [Ru(η(6)-C(6)H(5)(CH(2))(2)CH(3))(η(5)-C(5)(CH(3))(5))]BPh(4), [Ru(η(6)-C(6)H(5)CO(2)CH(2)CH(3))(η(5)-C(5)(CH(3))(5))]BF(4), [Ru(η(6)-C(10)H(8))(η(5)-(5) (CH(3))(5))]BPh(4), [Ru(η(6)-C(14)H(10))(η(5)-C(5)(CH(3))(5))]BPh(4), and [Ru(η(6)-C(16)H(10))(η(5)-C(5)(CH(3))(5))]BPh(4).
authors.affiliation: Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia. bradley.loughrey@griffithuni.edu.au
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Loughrey
authors.forename: Benjamin V
authors.initials: BV
authors.lastname: Cunning
authors.forename: Peter C
authors.initials: PC
authors.lastname: Healy
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Brown
authors.forename: Peter G
authors.initials: PG
authors.lastname: Parsons
authors.forename: Michael L
authors.initials: ML
authors.lastname: Williams
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D011789:Quantum Theory; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D012428:Ruthenium