Ruthenium polypyridyl complexes; their interaction with DNA and their role as sensitisers for its photocleavage

Kelly, John M.; McConnell, David J.; Ó'hUigín, Colm; Tossi, Alessandro B.; Mesmaeker, Andrée Kirsch-De; Masschelein, Axel; Nasielski, Jacques

doi:10.1039/c39870001821

Cited by 110 publications

(76 citation statements)

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Section: Resultssupporting

confidence: 90%

“…From these titrations, an unwinding angle of 30 f 11" per ruthenium bound is obtained for Ru-(bpy)2dppz2+. This value is consistent with those observed for other avid intercalating agents such as ethidium bromide (26") (Keller, 1975) and Ru(phen)2phi2+ (26") (Pyle et al, 1989).It should be noted that the agarose gel displaying the unwinding of pBR322 (Figure 1) has been visualized using Ru(bpy)2dppz2+ as a luminescent stain. The luminescence enhancement therefore is also clearly evident in gels.…”

supporting

confidence: 87%

“…The extent of DNA helix unwinding by a noncovalently bound species may be quantitated by examining the change in superhelical density in a plasmid after relaxation of the plasmid in the presence of bound complex with topoisomerase I (Keller, 1975;Waring, 1970; Kelly et al, 1985). Figure 1 shows the unwinding of pBR322 DNA by Ru(bpy)2dppz2+ following incubation with topoisomerase I in the presence of increasing amounts of ruthenium complex.…”

Section: Resultsmentioning

confidence: 99%

Section: Buffers and Chemicalsmentioning

confidence: 99%

“…Samples were electrophoresed in 0.7% agarose and visualized after incubation for 45 min with 5 X lo4 M Ru(bpy)2dppz2+; no destaining was required. The unwinding angles were determined from plots of -7 (the number of superhelical turns) vs the concentration of metal complex according to (Keller, 1975;Waring, 1970) t~ = -2Or,(@/360) = -rc@/18 where CT is the superhelical density of the plasmid, r, equals the amount of metal complex ions bound per nucleotide when all of the superhelices are removed, and @ is the unwinding angle. On the basis of the equilibrium dialysis experiments, added ruthenium concentrations in this assay could beassumed to be totally bound.…”

mentioning

confidence: 99%

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Characterization of dipyridophenazine complexes of ruthenium(II): The light switch effect as a function of nucleic acid sequence and conformation

Jenkins¹,

Friedman²,

Turro³

et al. 1992

Biochemistry

440

368

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Spectroscopic parameters for two novel ruthenium complexes on binding to nucleic acids of varying sequences and conformations have been determined. These complexes, R~( b p y )~d p p z~+ and Ru(phen)zdppz2+ (bpy = 2,2'-bipyridine; phen = 1,lO-phenanthroline; dppz = dipyrido[3,2:a-2',3':~]-phenazine) serve as "molecular light switches" for DNA, displaying no photoluminescence in aqueous solution but luminescing intensely in the presence of DNA. The luminescent enhancement observed upon binding is attributed to the sensitivity of the excited state to quenching by water; in DNA, the metal complex, upon intercalation into the helix, is protected from the aqueous solvent, thereby preserving the luminescence. Correlations between the extent of protection (depending upon the DNA conformation) and the luminescence parameters are observed. Indeed, the strongest luminescent enhancement is observed for intercalation into DNA conformations which afford the greatest amount of overlap with access from the major groove, such as in triple helices. Differences are observed in the luminescent parameters between the two complexes which also correlate with the level of water protection. In the presence of nucleic acids, both complexes exhibit biexponential decays in emission. Quenching studies are consistent with two intercalative binding modes for the dppz ligand from the major groove: one in which the metal-phenazine axis lies along the DNA dyad axis and another where the metal-phenazine axis lies almost perpendicular to the DNA dyad axis. Ru(bpy)zdppz2+ and Ru(phen)2dppzz+ are shown here to be unique reporters of nucleic acid structures and may become valuable in the design of new diagnostics for DNA.Considerable attention has been given to the design of small molecules that bind to DNA with site selectivity so as to develop novel therapeutics and chemical probes for nucleic acid sites and structures, as well as novel diagnostic agents targeted to double-helical DNA (Pyle & Dervan, 1986;Moser & Dervan, 1987;Hecht, 1986;Tullius, 1988). Our laboratory has focused in part on the development of transitionmetal complexes as probes of nucleic acid structure (Chow & Barton, 1992;Mei & Barton, 1986;Kirshenbaum et al., 1988;Barton, 1986). We have found that ruthenium complexes serve as very sensitive luminescent reporters of DNA in aqueous solution and may become particularly useful in developing new diagnostics.Ruthenium complexes are ideally suited for application as sensitive noncovalent probes for polymer structure. The complexes are water-soluble, coordinatively saturated, and inert to substitution. Polypyridyl complexes of ruthenium-(11) furthermore are intensely colored owing to a wellcharacterized, localized metal-to-ligand charge transfer (MLCT) transition (Juris et al., 1988). Importantly, this transition is perturbed on binding to DNA, providing a sensitive spectroscopic handle for interactions with nucleic acids (Pyle et al., 1989). Tris( 1 ,IO-phenanthroline)ruthenium(II), Ru-(phen)j2+, has been established, primar...

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Section: Resultssupporting

confidence: 90%

supporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Buffers and Chemicalsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Characterization of dipyridophenazine complexes of ruthenium(II): The light switch effect as a function of nucleic acid sequence and conformation

Jenkins¹,

Friedman²,

Turro³

et al. 1992

Biochemistry

440

368

View full text Add to dashboard Cite

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Probing DNA Using Metal Complexes

Marcélis¹,

Vanderlinden²,

Mesmaeker³

2014

Inorganic Chemical Biology

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Die CH‐Bindungen der Zuckerbausteine von DNA als Angriffspunkte für chemische Nucleasen und Wirkstoffe

1995

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Diese Ubersicht befafit sich mit den mo-und seiner Intercalation in DNA wird lekularen Aspekten der DNA-Spaltung eine andere der fiinf aktivierbaren C-Hdurch synthetische chemische Nucleasen Bindungen der Desoxyribose angegrif-(Ubergangsmetallkomplexe rnit Redox-fen. In Folgereaktionen an der ureigenschaften und Affinitat zu DNA) spriinglichen Schadigungsstelle werden und natiirliche Wirkstoffe (cytotoxische Nucleobasen freigesetzt, Zuckerreste Agentien wie Bleomycine und Endiine) . oxidiert, Basen-substituierte oxidierte Anders als die Desoxyribo-Nucleasen, Zucker oder an die endstandige Phosdie den nucleophilen Angriff von Wasser phatgruppe gebundene oxidierte Zucker auf das Phosphoratom einer bestimmten gebildet. In den rneisten Fallen verurPhosphodiester-Einheit katalysieren, oxi-sacht vor allem der Verlust eines Nucleodieren diese nicht hydrolytisch wirken-sids oder zumindest eines Teils davon den Reagentien zur DNA-Spaltung die rnit dem darnit einhergehenden Verlust Zuckereinheiten, und zwar im allgemei-einer Baseninformation den DNAnen durch H-Abstraktion. Je nach der Strangbruch. Fur beide Arten von Art und der Struktur des Spaltungsre-DNA-Spaltungsreagentien wird hier der agens sowie der Art seiner Aktivierung derzeitige Wissensstand hinsichtlich der Art der Aktivierung und der DNA-Bindung sowie des Mechanismus des oxidativen Desoxyribose-Abbaus vorgestellt. Dank eines genaueren Verstandnisses der unterschiedlichen DNA-Spaltungsmechanismen und wegen der Nachfrage nach hocheffizienten und hochspezifischen Reagentien scheint die Entwicklung neuer kiinstlicher und selektiver DNA-Spaltungsreagentien ein herausforderndes Arbeitsgebiet auf dem Weg zu einem rationalen Design neuartiger Antitumor-und antiviraler Agentien sowie in der Molekularbiologie zu sein. Stichworte:Bleomycin . DNA-Spaltung . Endiine . Ubergangsmetallkomplexe

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Ruthenium polypyridyl complexes; their interaction with DNA and their role as sensitisers for its photocleavage

Cited by 110 publications

References 0 publications

Characterization of dipyridophenazine complexes of ruthenium(II): The light switch effect as a function of nucleic acid sequence and conformation

Characterization of dipyridophenazine complexes of ruthenium(II): The light switch effect as a function of nucleic acid sequence and conformation

Probing DNA Using Metal Complexes

Die CH‐Bindungen der Zuckerbausteine von DNA als Angriffspunkte für chemische Nucleasen und Wirkstoffe

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