DNA-binding and photoactivated enantiospecific cleavage of chiral polypyridyl ruthenium(II) complexes
Introduction
There has been considerable interest in DNA endonucleolytic cleavage reactions that are activated by complexes, as these may provide useful information for the preparation of “footprinting” reagents and design of novel photonucleases [1], [2], [3]. The features common to these complexes are that the molecule has a high binding affinity for double-stranded DNA and that the molecule binds a redox-active metal ion cofactor. Upon irradiation, it can generate oxygen or hydroxyl radicals, thus induces single-strand or double-strand cleavage of DNA. During the past decade, the interaction of ruthenium(II) polypyridyl complexes with DNA has received considerable attention [4], [5], [6], [7]. In comparison with other metal complexes, these complexes can bind to DNA by intercalation with high binding affinity, and significant changes on their photophysical properties can be observed after binding to DNA. Furthermore, these inert chiral complexes have Δ- and Λ-isomers, which usually display different binding affinity for the right-handed B-DNA due to the different steric constrains imposed on the isomers. This difference makes these complexes possible structural probe to determine B-DNA and Z-DNA. In addition, upon irradiation, these chiral complexes can promote DNA cleavage, and they also exhibited obvious enantioselectivity in DNA cleavage [1], [8], which is very helpful for the understanding of the mechanisms of DNA cleavage and the design of new clinic anti-cancer drugs. However, in the past reports, fewer detailed the interactions of individual enantiomers with DNA [9], [10], and fewer reports detailed the photoactivated enantiospecific DNA cleavage by structure related enantiomers. Herein we reported the syntheses and characterization of a series of structure related chiral ruthenium(II) complexes Δ- and Λ-[Ru(bpy)2CNOIP](PF6)2 (Δ-1 and Λ-1; bpy=2,2′-bipyridine, CNOIP=2-(2-chloro-5-nitrophenyl)imidazo[4,5-f][1,10]phenanthroline), Δ- and Λ-[Ru(bpy)2HPIP](PF6)2 (Δ-2 and Λ-2; HPIP = 2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline), Δ- and Λ-[Ru(bpy)2DPPZ](PF6)2 (Δ-3 and Λ-3; DPPZ=dipyrido[3,2:a-2′,3′:c]phenazine), Δ- and Λ-[Ru(bpy)2TAPTP](PF6)2 (Δ-4 and Λ-4; TAPTP=4,5,9,18-tetraazaphenanthreno[9,10-b]triphenylene), their structures were shown in Fig. 1. Their binding to calf thymus DNA has been studied by electronic absorption, steady-state emission, viscosity and equibrium dialysis experiments. The abilities of each enantiomer to induce the cleavage of pBR 322 DNA were investigated, the mechanisms for cleavage were also proposed. These studies should be valuable for the further clarification of binding nature of chiral complexes to DNA, and provide useful information for the design of novel photonucleases.
Section snippets
Chemicals
All reagents were purchased commercially and used without further purification unless otherwise noted. All the spectroscopic titration was carried out in aerated buffer (5 mM Tris–HCl, 50 mM NaCl, pH 7.2) at room temperature. A solution of CT-DNA in the buffer gave a ratio of UV absorbance at 260 and 280 nm of ca. 1.8–1.9:1, indicating that the DNA was sufficiently free of protein [11]. The DNA concentration was determined by absorption spectroscopy using the molar absorption coefficient (6600 M
DNA-binding studies
It is a general observation that the binding of intercalative molecules to DNA is accompanied by a red shift and hypochromism in the absorption spectra, and also it often appears that the extent of spectral change is related to the strength of binding (but not in all cases), and the spectra for intercalators are more perturbed than those for groove binders. In our studies, the binding of Δ- and Λ-isomers to CT-DNA led to hypochromism and red shifts in the metal-to-ligand charge transfer (MLCT)
Conclusions
For the series of enantiomeric polypyridyl ruthenium(II) complexes 1–4, the spectroscopic and viscosity results indicated that they all bound to DNA through an intercalative mode, but the binding affinity of each complex to DNA was different due to the different shape and planarity of the intercalating ligand. After binding to DNA, the luminescence properties of complex 1 were distinctly different from the other three complexes, indicating that the photophysical properties of the complexes
Abbreviations
- bpy
2,2′-bipyridine
- phen
1,10-phenanthroline
- HPIP
2-(2-hydroxyphenyl)imidazo[4,5-f] [1,10]phenanthroline
- CNOIP
2-(2-chloro-5-nitrophenyl)imidazo[4,5-f][1,10]phenanthroline
- TAPTP
4,5,9,18-tetraazaphenanthreno[9,10-b]triphenylene
- DPPZ
dipyrido[3,2:a-2′,3′:c] phenazine
- PPZ
4′,7′-phenanthrolino[5′,6′:2,3]pyrazine
- CT DNA
calf thymus DNA
- Tris
tris(hydroxymethyl)aminomethane
- UV–Vis
UV–Visible
- IL
intraligand
- MLCT
metal-to-ligand charge transfer
Acknowledgements
We are grateful to Shenzhen Science and Technology Foundation for their financial support.
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