Photochemistry of Ru(II) Triazole Complexes with 6-Membered Chelate Ligands: Detection and Reactivity of Ligand-Loss Intermediates.

Photochemical ligand release from metal complexes may be exploited in the development of novel photoactivated chemotherapy agents for the treatment of cancer and other diseases. Highly intriguing photochemical behavior is reported for two ruthenium(II) complexes bearing conformationally flexible 1,2,3-triazole-based ligands incorporating a methylene spacer to form 6-membered chelate rings. [Ru(bpy)2(pictz)]2+ (1) and [Ru(bpy)2(btzm)]2+ (2) (bpy = 2,2'-bipyridyl; pictz = 1-(picolyl)-4-phenyl-1,2,3-triazole; btzm = bis(4-phenyl-1,2,3-triazol-4-yl)methane) exhibit coordination by the triazole ring through the less basic N2 atom as a consequence of chelation and readily undergo photochemical release of the pictz and btzm ligands (ϕ = 0.079 and 0.091, respectively) in acetonitrile solution to form cis-[Ru(bpy)2(NCMe)2]2+ (3) in both cases. Ligand-loss intermediates of the form [Ru(bpy)2(κ1-pictz or κ1-btzm)(NCCD3)]2+ are detected by 1H NMR spectroscopy and mass spectrometry. Photolysis of 1 yields three ligand-loss intermediates with monodentate pictz ligands, two of which form through simple decoordination of either the pyridine or triazole donor with subsequent solvent coordination (4-tz(N2) and 4-py, respectively). The third intermediate, shown to be able to form photochemically directly from 1, arises through linkage isomerism in which the monodentate pictz ligand is coordinated by the triazole N3 atom (4-tz(N3)) with a comparable ligand-loss intermediate with an N3-bound κ1-btzm ligand also observed for 2.

G-Quadruplex Binding of an NIR Emitting Osmium Polypyridyl Probe Revealed by Solution NMR and Time-Resolved Infrared Studies.

G-quadruplexes are emerging targets in cancer research and understanding how diagnostic probes bind to DNA G-quadruplexes in solution is critical to the development of new molecular tools. In this study the binding of an enantiopure NIR emitting [Os(TAP)2 (dppz)]2+ complex to different G-quadruplex structures formed by human telomer (hTel) and cMYC sequences in solution is reported. The combination of NMR and time-resolved infrared spectroscopic techniques reveals the sensitivity of the emission response to subtle changes in the binding environment of the complex. Similar behaviour is also observed for the related complex [Os(TAP)2 (dppp2)]2+ upon quadruplex binding.

Photophysical Properties and DNA Binding of Two Intercalating Osmium Polypyridyl Complexes Showing Light-Switch Effects.

The synthesis and photophysical characterization of two osmium(II) polypyridyl complexes, [Os(TAP)2dppz]2+ (1) and [Os(TAP)2dppp2]2+ (2) containing dppz (dipyrido[3,2-a:2',3'-c]phenazine) and dppp2 (pyrido[2',3':5,6]pyrazino[2,3-f][1,10]phenanthroline) intercalating ligands and TAP (1,4,5,8-tetraazaphenanthrene) ancillary ligands, are reported. The complexes exhibit complex electrochemistry with five distinct reductive redox couples, the first of which is assigned to a TAP-based process. The complexes emit in the near-IR (1 at 761 nm and 2 at 740 nm) with lifetimes of >35 ns with a low quantum yield of luminescence in aqueous solution (∼0.25%). The Δ and Λ enantiomers of 1 and 2 are found to bind to natural DNA and with AT and GC oligodeoxynucleotides with high affinities. In the presence of natural DNA, the visible absorption spectra are found to display significant hypochromic shifts, which is strongly evident for the ligand-centered π-π* dppp2 transition at 355 nm, which undergoes 46% hypochromism. The emission of both complexes increases upon DNA binding, which is observed to be sensitive to the Δ or Λ enantiomer and the DNA composition. A striking result is the sensitivity of Λ-2 to the presence of AT DNA, where a 6-fold enhancement of luminescence is observed and reflects the nature of the binding for the enantiomer and the protection from solution. Thermal denaturation studies show that both complexes are found to stabilize natural DNA. Finally, cellular studies show that the complexes are internalized by cultured mammalian cells and localize in the nucleus.

Quenching of the phosphorescence of thermally reversible photochromic naphthopyran Re(i) complexes initiated by either visible or ultraviolet radiation.

Re(i) complexes bearing thermally reversible photochromic naphthopyran axial ligands undergo highly efficient, reversible phosphorescence quenching actuated by either visible or UV irradiation. The photoinduced quenching of the triplet metal-to-ligand charge-transfer (3MLCT) emission is interpreted based on changes in the relative energies of the excited states.

Photophysical and Cellular Imaging Studies of Brightly Luminescent Osmium(II) Pyridyltriazole Complexes.

The series of complexes [Os(bpy)3- n(pytz) n][PF6]2 (bpy = 2,2'-bipyridyl, pytz = 1-benzyl-4-(pyrid-2-yl)-1,2,3-triazole, 1 n = 0, 2 n = 1, 3 n = 2, 4 n = 3) were prepared and characterized and are rare examples of luminescent 1,2,3-triazole-based osmium(II) complexes. For 3 we present an attractive and particularly mild preparative route via an osmium(II) η6-arene precursor circumventing the harsh conditions that are usually required. Because of the high spin-orbit coupling constant associated with the Os(II) center the absorption spectra of the complexes all display absorption bands of appreciable intensity in the range of 500-700 nm corresponding to spin-forbidden ground-state-to-3MLCT transitions (MLCT = metal-to-ligand charge transfer), which occur at significantly lower energies than the corresponding spin-allowed 1MLCT transitions. The homoleptic complex 4 is a bright emitter (λmaxem = 614 nm) with a relatively high quantum yield of emission of ∼40% in deoxygenated acetonitrile solutions at room temperature. Water-soluble chloride salts of 1-4 were also prepared, all of which remain emissive in aerated aqueous solutions at room temperature. The complexes were investigated for their potential as phosphorescent cellular imaging agents, whereby efficient excitation into the 3MLCT absorption bands at the red side of the visible range circumvents autofluorescence from biological specimens, which do not absorb in this region of the spectrum. Confocal microscopy reveals 4 to be readily taken up by cancer cell lines (HeLa and EJ) with apparent lysosomal and endosomal localization, while toxicity assays reveal that the compounds have low dark and light toxicity. These complexes therefore provide an excellent platform for the development of efficient luminescent cellular imaging agents with advantageous photophysical properties that enable excitation and emission in the biologically transparent region of the optical spectrum.

Mitochondria-localising DNA-binding biscyclometalated phenyltriazole iridium(iii) dipyridophenazene complexes: syntheses and cellular imaging properties.

Two new biscyclometalated complexes [Ir(ptzR)2(dppz)]+ (dppz = dipyridophenazene; ptzRH = 4-phenyl-1-benzyl-1,2,3-triazole (1+) and 4-phenyl-1-propyl-1,2,3-triazole (2+)) have been prepared. The hexafluorophosphate salts of these complexes have been fully characterized and, in one case, the X-ray structure of a nitrate salt was obtained. The DNA binding properties of the chloride salts of the complexes were investigated, as well as their cellular uptake by A2780 and MCF7 cell lines. Both complexes display an increase in the intensity of phosphorescence upon titration with duplex DNA, indicating the intercalation of the dppz ligand and, given that they are monocations, the complexes exhibit appreciable DNA binding affinity. Optical microscopy studies reveal that both complexes are taken up by live cancer cell lines displaying cytosol based luminescence. Colocalization studies with commercial probes show high Pearson coefficients with mitotracker dyes confirming that the new complexes specifically localize on mitochondria.

Towards Water Soluble Mitochondria-Targeting Theranostic Osmium(II) Triazole-Based Complexes.

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. Complex 1 exhibits 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. Complex 1 underwent counterion metathesis to yield [Os(btzpy)2]Cl2 (1Cl), which shows near identical optical absorption and emission spectra to those of 1. Direct measurement of the yield of singlet oxygen sensitised by 1Cl was 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. Complex 1Cl readily 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 on 1 therefore present an excellent platform for the development of novel theranostic agents for anticancer activity.