title: Towards Water Soluble Mitochondria-Targeting Theranostic Osmium(II) Triazole-Based Complexes.
abstract: The complex [Os(btzpy)₂][PF₆]₂ (1, btzpy = 2,6-bis(1-phenyl-1,2,3-triazol-4-yl)pyridine) has been prepared and characterised. Complex1exhibits phosphorescence (λem= 595 nm, τ = 937 ns, φem= 9.3% in degassed acetonitrile) in contrast to its known ruthenium(II) analogue, which is non-emissive at room temperature. The complex undergoes significant oxygen-dependent quenching of emission with a 43-fold reduction in luminescence intensity between degassed and aerated acetonitrile solutions, indicating its potential to act as a singlet oxygen sensitiser. Complex1underwent counterion metathesis to yield [Os(btzpy)₂]Cl₂ (1Cl), which shows near identical optical absorption and emission spectra to those of1. Direct measurement of the yield of singlet oxygen sensitised by1Clwas carried out (φ (¹O₂) = 57%) for air equilibrated acetonitrile solutions. On the basis of these photophysical properties, preliminary cellular uptake and luminescence microscopy imaging studies were conducted. Complex1Clreadily entered the cancer cell lines HeLa and U2OS with mitochondrial staining seen and intense emission allowing for imaging at concentrations as low as 1 μM. Long-term toxicity results indicate low toxicity in HeLa cells with LD50 >100 μM. Osmium(II) complexes based on1therefore present an excellent platform for the development of novel theranostic agents for anticancer activity.
authors.affiliation: Department of Chemistry, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK. Salem.Omar@hud.ac.uk.
authors.forename: Salem A E
authors.initials: SA
authors.lastname: Omar
authors.affiliation: Department of Chemistry, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK. P.Scattergood@hud.ac.uk.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Scattergood
authors.affiliation: Department of Chemistry, Dainton Building, University of Sheffield, Sheffield S3 7HF, UK. lkmckenzie1@sheffield.ac.uk.|Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK. lkmckenzie1@sheffield.ac.uk.
authors.forename: Luke K
authors.initials: LK
authors.lastname: McKenzie
authors.affiliation: Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK. h.bryant@sheffield.ac.uk.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Bryant
authors.affiliation: Department of Chemistry, Dainton Building, University of Sheffield, Sheffield S3 7HF, UK. julia.weinstein@sheffield.ac.uk.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Weinstein
authors.affiliation: Department of Chemistry, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK. p.i.elliott@hud.ac.uk.
authors.forename: Paul I P
authors.initials: PI
authors.lastname: Elliott
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008163:Luminescent Measurements; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009992:Osmium / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry; D012995:Solubility; D000068936:Theranostic Nanomedicine; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D009942:Organometallic Compounds; D014230:Triazoles; D014867:Water; D026082:Singlet Oxygen; D009992:Osmium
keywords: anticancer; complexes; ligands; osmium; oxygen sensitizer; photophysics; triazole