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

Abstract

The synthesis and photophysical characterization of two osmium(II) polypyridyl complexes, [Os(TAP) 2 dppz] 2+ ( 1 ) and [Os(TAP) 2 dppp2] 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.

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

“…Notably, complex 2 possesses a well resolved π!π* ligand centred dppp2 transition at 355 nm, which allows direct reporting on the influence of the extended polypyridyl ligand on the surrounding bases in the G4 binding environment. [19] Interestingly, these measurements again suggest that the emission is very sensitive to subtilties in the particular binding interactions. This can be clearly seen by comparing the spectra obtained for Λ-2 and Δ-2 in the presence of excess cMYC G4 (Figure S16).…”

“…Complex 1 displays weak phosphorescence at 750 nm in aqueous solution [19] . This emission is found to be enhanced in the presence of increasing concentrations of both hTel and cMYC G4 structures, which is accompanied by modest changes in the visible absorption spectrum associated with the MLCT transition (Figures 2 and S1‐S2).…”

“…For this system the role of one electron oxidation of the bases can be ruled out due to the absence of emission quenching and also the low Os II/III oxidation potential (+ 1.39 V vs. Ag/AgCl). [19] Furthermore, the 400 nm excitation cannot directly excite DNA. For these reasons the new transient is assigned to a perturbation of the thymine carbonyl (ν C4 = O4 ) and guanine vibrations, which results in a shift in the absorption of the ground state vibration.…”

“…We have recently reported that both 1 and 2 show enhanced luminescence in the presence of double stranded DNA and that subtle changes to the intercalating ligand, dppz versus dppp2, modulates the enhancement response to AT compared to GC DNA. [19] Notably, the extended dppz ligand is capable of forming favourable stacking inter-actions with G4 structures. [18c] This ability to stack with guanine quartets was investigated for two different G4 structures (i) the parallel-type structure, formed by a sequence derived from the cMYC promoter and (ii) the hybrid-type formed by the hTel sequence.…”

“…In the current study, we show the importance of combining structural and photophysical studies, to resolve the impact of G4 binding on the luminescence response of the enantiomers of the osmium tetraazaphenanthrene (TAP) probe [Os(TAP) 2 (dppz)] 2+ ( 1 ) and the isostructural [Os(TAP) 2 (dppp2)] 2+ (dppp2 = pyrido[2′,3′:5,6]pyrazino[2,3‐ f ][1,10]phenanthroline) ( 2 ), see Figure 1. We have recently reported that both 1 and 2 show enhanced luminescence in the presence of double stranded DNA and that subtle changes to the intercalating ligand, dppz versus dppp2, modulates the enhancement response to AT compared to GC DNA [19] . Notably, the extended dppz ligand is capable of forming favourable stacking interactions with G4 structures [18c] .…”