title: Targeting the endoplasmic reticulum with a membrane-interactive luminescent ruthenium(ii) polypyridyl complex†Electronic supplementary information (ESI) available: Experimental details, characterization of2and Fig. S1-S6. See DOI: 10.1039/c3sc51725jClick here for additional data file.
abstract: The characterization and bioactivity of the dinuclear ruthenium(ii) complex [(Ru(DIP)2)2(tpphz)]4+(DIP = 4,7-diphenyl-1,10-phenanthroline and tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) is reported. This new complex is found to be luminescent in acetonitrile, where excitation into MLCT (metal-to-ligand charge-transfer) bands in the visible area of the spectrum (λex= 450 nm,ε= 45 000 M-1cm-1) result in red emission (λem,max= 620 nm,ΦMLCT= 0.017). Aqueousin vitrobinding studies indicate that this complex binds to duplex DNA with an affinity of 1.8 × 106M-1through a non-classical groove-binding interaction, however, unlike the parent complex [(Ru(phen)2)2(tpphz)]4+(phen = 1,10-phenanthroline), it also displays an increase in MLCT luminescence on addition of liposomes. Confocal microscopy and TEM studies show that this lipophilic complex targets the endoplasmic reticulum of eukaryotic cells, where it functions as an imaging agent for this organelle, and cytotoxicity studies in human cancer cell lines indicate a comparable potency to the anti-cancer drug cisplatin.
authors.affiliation: Department of Chemistry , University of Sheffield , Sheffield , UK . Email: james.thomas@sheffield.ac.uk ; ; Tel: +44 (0)114 22 29325 ; Department of Biomedical Science , University of Sheffield , Sheffield , UK . Email: c.g.w.smythe@sheffield.ac.uk ; Fax: +44 (0)114 222 2787 ; Tel: +44 (0)114 222 2320.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Gill
authors.affiliation: Department of Chemistry , University College London , London , UK . Email: g.battaglia@ucl.ac.uk ; Tel: +44 (0)20 7679 4623.
authors.forename: Denis
authors.initials: D
authors.lastname: Cecchin
authors.affiliation: Department of Chemistry , University of Sheffield , Sheffield , UK . Email: james.thomas@sheffield.ac.uk ; ; Tel: +44 (0)114 22 29325.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Walker
authors.affiliation: Department of Chemistry , University of Sheffield , Sheffield , UK . Email: james.thomas@sheffield.ac.uk ; ; Tel: +44 (0)114 22 29325.
authors.forename: Raminder S
authors.initials: RS
authors.lastname: Mulla
authors.affiliation: Department of Chemistry , University College London , London , UK . Email: g.battaglia@ucl.ac.uk ; Tel: +44 (0)20 7679 4623.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
authors.affiliation: Department of Biomedical Science , University of Sheffield , Sheffield , UK . Email: c.g.w.smythe@sheffield.ac.uk ; ; Tel: +44 (0)114 222 2320.
authors.forename: Carl
authors.initials: C
authors.lastname: Smythe
authors.affiliation: Department of Chemistry , University of Sheffield , Sheffield , UK . Email: james.thomas@sheffield.ac.uk ; ; Tel: +44 (0)114 22 29325.
authors.forename: Jim A
authors.initials: JA
authors.lastname: Thomas