Molecular “Light Switch” for DNA: Ru(bpy)2(dppz)2+.
TL;DR: In this paper, a transition-metal complex was used as a molecular light switch for double-helical DNA, which showed no photoluminescence in aqueous solution at ambient temperatures.
Abstract: Considerable research has focused on the development of nonradioactive probes for nucleic acids. Extensive photophysical studies indicate that Ru(phen){sub 3}{sup 2+} bound to double-helical DNA displays an increase in luminescence owing to intercalation; emission from the metal-to-ligand charge transfer (MLCT) excited state decays as a biexponential with one lifetime of 2 {mu}s attributed to the intercalative form and a second lifetime of 0.6 {mu}s (indistinguishable from the free species) assigned to the surface bound form. Here we report the application of a novel transition-metal complex as a true molecular light switch for DNA. This probe is Ru(bpy){sub 2}(dppz){sup 2+} (bpy = 2,2{prime}-bipyridine, dppz = dipyrido(3,2-a:2{prime},3{prime}-c)phenazine), which shows no photoluminescence in aqueous solution at ambient temperatures, but displays intense photoluminescence in the presence of double-helical DNA, to which the complex binds avidly.
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TL;DR: A dinuclear ruthenium(II) polypyridyl system that works as a multifunctional biological imaging agent staining the DNA of eukaryotic and prokaryotic cells for both luminescence and transition electron microscopy is presented.
Abstract: In the search for new biological imaging agents, metal coordination compounds able to emit from triplet metal-to-ligand charge transfer (MLCT) states offer many advantages as luminescent probes of DNA structure. However, poor cellular uptake restricts their use in live cells. Here, we present a dinuclear ruthenium(II) polypyridyl system that works as a multifunctional biological imaging agent staining the DNA of eukaryotic and prokaryotic cells for both luminescence and transition electron microscopy. This MLCT 'light switch' complex directly images nuclear DNA of living cells without requiring prior membrane permeabilization. Furthermore, inhibition and transmission electron microscopy studies show this to be via a non-endocytotic, but temperature-dependent, mechanism of cellular uptake in MCF-7 cells, and confocal microscopy reveals multiple emission peaks that function as markers for cellular DNA structure.
421 citations
TL;DR: The group recently demonstrated that Ru(bphen)2(benzene-1,2-dislufinate)] (bphen = 4,7-diphenyl- 1,10-phenanthroline) localizes in mitochondria and has an IC50 value of 0.62 μM with a PI of over 80 in HeLa cells upon light irradiation at 420 nm.
Abstract: ConspectusPhotodynamic Therapy (PDT) is an emerging technique to treat certain types of cancer, bacterial, fungal, and viral infections, and skin diseases. In past years, different research groups developed new ruthenium-containing photosensitizers (PSs) with tuned photophysical and biological properties to better fit the requirements of PDT. In this Account, we report and discuss the latest results in this research area, emphasizing particularly our own research. For example, inspired by the DNA intercalating complex [Ru(bpy)2(dppz)]2+ (bpy = 2,2′-bipyridine; dppz = (dipyrido[3,2-a:2′,3′-c]phenazine), a series of ruthenium complexes bearing differently functionalized dppz ligands were synthesized to target DNA. The introduction of the substituents on the dppz ligand did not reduce much the affinity of the complexes to DNA but highly affected their cellular uptake. The most effective complex in this series, [Ru(bpy)2(dppz-7-OMe)]2+, showed IC50 values in the low micromolar range against several types of c...
387 citations
TL;DR: High DNA binding affinity of [Ru(bpy)(phpy)(dppz)](+) resulted in effective disruption of the binding of transcription factor NF-κB to DNA sequences, thereby inhibiting cellular transcription and leading to irreversible cancer cell apoptosis.
Abstract: Recently, coordinatively saturated and substitutionally inert Ru(II) complexes have been investigated as anticancer agents. Herein a cyclometalated Ru(II) complex, [Ru(bpy)(phpy)(dppz)]+, was found to be rapidly taken up by cancer cells, and nearly 90% of the complex accumulated in the nuclei of cancer cells after a 2 h incubation. The anticancer activity of this complex was screened against a panel of cancer cell lines. Remarkably, it exhibited IC50 values that were an order of magnitude lower than those of cisplatin. This complex also displayed potencies superior to those of cisplatin against 3D tumor spheroids. Further studies revealed that the high DNA binding affinity of [Ru(bpy)(phpy)(dppz)]+ resulted in effective disruption of the binding of transcription factor NF-κB to DNA sequences, thereby inhibiting cellular transcription and leading to irreversible cancer cell apoptosis. Our work provides new insights into understanding the biological interactions and anticancer molecular mechanisms of DNA-sp...
198 citations
TL;DR: The graphene oxide (GO) interaction with DNA molecules is explored systematically using fluorescence spectroscopic and circular dichroism studies, gel electrophoresis, and DNA thermal denaturation to reveal that the GO nanosheets could intercalate efficiently into DNA molecules.
Abstract: The exploration of efficient DNA intercalative agents (intercalators) is essential for understanding DNA scission, repair, and signal transduction. In this work, we explored systematically the graphene oxide (GO) interaction with DNA molecules using fluorescence spectroscopic (FL) and circular dichroism (CD) studies, gel electrophoresis, and DNA thermal denaturation. We demonstrated that the GO nanosheets could intercalate efficiently into DNA molecules. Significantly, we illustrated that the scission of DNA by GO sheets combining with copper ions could take place pronouncedly. The scission of DNA by the GO/Cu(2+) system is critically dependent on the concentrations of GO and Cu(2+) and their ratio. DNA cleavage ability exhibited by the GO with several other metal ions and the fact that GO/Cu(2+)-cleaved DNA fragments can be partially relegated suggest that the mechanism of DNA cleavage by the GO/metal ion system is oxidative and hydrolytic. The result reveals that the GO/Cu(2+) could be used as a DNA cleaving system that should find many practical applications in biotechnology and as therapeutic agents.
150 citations
Cites background from "Molecular “Light Switch” for DNA: R..."
...throline and porphyrin were efficient DNA cleaving agents.(9,10) Increasing the surface...
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...finity, hence an increase in its DNA cleavage activity.(9) In addition, the dimension of the...
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TL;DR: In this paper, the concept of charge transfer numbers is introduced and applied to characterize the excited states of transition metal complexes, including metal-centered, intra-ligand charge transfer, ligand-to-metal charge transfer.
100 citations
Cites background from "Molecular “Light Switch” for DNA: R..."
...A very interesting class of TMCs is based on the complex [Ru(bipy)2(dppz)] (bipy = 2,2’-bipyridine, dppz = dipyrido-[3,2-a:2’,3’-c]-phenazine), which has been reported as a molecular light switch for DNA in 1990 [150]....
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TL;DR: In this article, a transition-metal complex was used as a molecular light switch for double-helical DNA, which showed no photoluminescence in aqueous solution at ambient temperatures.
Abstract: Considerable research has focused on the development of nonradioactive probes for nucleic acids. Extensive photophysical studies indicate that Ru(phen){sub 3}{sup 2+} bound to double-helical DNA displays an increase in luminescence owing to intercalation; emission from the metal-to-ligand charge transfer (MLCT) excited state decays as a biexponential with one lifetime of 2 {mu}s attributed to the intercalative form and a second lifetime of 0.6 {mu}s (indistinguishable from the free species) assigned to the surface bound form. Here we report the application of a novel transition-metal complex as a true molecular light switch for DNA. This probe is Ru(bpy){sub 2}(dppz){sup 2+} (bpy = 2,2{prime}-bipyridine, dppz = dipyrido(3,2-a:2{prime},3{prime}-c)phenazine), which shows no photoluminescence in aqueous solution at ambient temperatures, but displays intense photoluminescence in the presence of double-helical DNA, to which the complex binds avidly.
1,291 citations