title: Cellular delivery of pyrenyl-arene ruthenium complexes by a water-soluble arene ruthenium metalla-cage.
abstract: Three pyrenyl-arene ruthenium complexes (M(1)-M(3)) of the general formula [Ru(η(6)-arene-pyrenyl)Cl(2)(pta)] (pta = 1,3,5-triaza-7-phosphaadamantane) have been synthesised and characterised. Prior to the coordination to ruthenium, pyrene was connected to the arene ligand via an alkane chain containing different functional groups: ester (L(1)), ether (L(2)) and amide (L(3)), respectively. Furthermore, the pyrenyl moieties of the M(n) complexes were encapsulated within the hydrophobic cavity of the water soluble metalla-cage, [Ru(6)(η(6)-p-cymene)(6)(tpt)(2)(donq)(3)](6+) (tpt = 2,4,6-tri-(pyridin-4-yl)-1,3,5-triazine; donq = 5,8-dioxydo-1,4-naphthoquinonato), while the arene ruthenium end was pointing out of the cage, thus giving rise to the corresponding host-guest systems [M(n)⊂Ru(6)(η(6)-p-cymene)(6)(tpt)(2)(donq)(3)](6+) ([M(n)⊂cage](6+)). The antitumor activity of the pyrenyl-arene ruthenium complexes (M(n)) and the corresponding host-guest systems [M(n)⊂cage][CF(3)SO(3)](6) were evaluated in vitro in different types of human cancer cell lines (A549, A2780, A2780cisR, Me300 and HeLa). Complex M(2), which contains an ether group within the alkane chain, demonstrated at least a 10 times higher cytotoxicity than the reference compound [Ru(η(6)-p-cymene)Cl(2)(pta)] (RAPTA-C). All host-guest systems [M(n)⊂cage](6+) showed good anticancer activity with IC(50) values ranging from 2 to 8 μM after 72 h exposure. The fluorescence of the pyrenyl moiety allowed the monitoring of the cellular uptake and revealed an increase of uptake by a factor two of the M(2) complex when encapsulated in the metalla-cage [Ru(6)(η(6)-p-cymene)(6)(tpt)(2)(donq)(3)](6+).
authors.affiliation: Institute of Chemistry, University of Neuchatel, Ave de Bellevaux 51, CH-2000 Neuchatel, Switzerland.
authors.forename: Mona Anca
authors.initials: MA
authors.lastname: Furrer
authors.forename: Frédéric
authors.initials: F
authors.lastname: Schmitt
authors.forename: Michaël
authors.initials: M
authors.lastname: Wiederkehr
authors.forename: Lucienne
authors.initials: L
authors.lastname: Juillerat-Jeanneret
authors.forename: Bruno
authors.initials: B
authors.lastname: Therrien
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011721:Pyrenes / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011721:Pyrenes; D014867:Water; D012428:Ruthenium; C030984:pyrene