DNA photocleavage by phenanthrenequinone diimine complexes of rhodium(III): shape-selective recognition and reaction

Sitlani, Ayesha; Long, Eric C.; Pyle, Anna Marie; Barton, Jacqueline K.

doi:10.1021/ja00033a003

Cited by 384 publications

(331 citation statements)

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“…The overall differences apparent with the A form compared to B-DNA also support intercalation by these ruthenium complexes from the major groove; other metallointercalators had been shown to bind DNA from the major groove using crystallography (Wang et al, 1978) and in DNA cleavage experiments (Sitlani et al, 1992).…”

Section: [R(au)ipol~[r(au)l "Pared To Pol~[d(at)lpol~[d(at)llmentioning

confidence: 91%

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

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440

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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: [R(au)ipol~[r(au)l "Pared To Pol~[d(at)lpol~[d(at)llmentioning

confidence: 91%

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

Self Cite

440

368

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“…Likely, then, without light the metalmismatch complex provides a secondary signal for protein binding or activation. It should also be noted that light activation of the metal complex generates only a short-lived ligand radical; thus, intimate association of the rhodium complex with its target is needed for a light-dependent reaction (22).…”

Section: Discussionmentioning

confidence: 99%

DNA mismatch-specific targeting and hypersensitivity of mismatch-repair-deficient cells to bulky rhodium(III) intercalators

Hart

Glebov

Ernst

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Mismatch repair (MMR) is critical to maintaining the integrity of the genome, and deficiencies in MMR are correlated with cancerous transformations. Bulky rhodium intercalators target DNA base mismatches with high specificity. Here we describe the application of bulky rhodium intercalators to inhibit cellular proliferation differentially in MMR-deficient cells compared with cells that are MMR-proficient. Preferential inhibition by the rhodium complexes associated with MMR deficiency is seen both in a human colon cancer cell line and in normal mouse fibroblast cells; the inhibition of cellular proliferation depends strictly on the MMR deficiency of the cell. Furthermore, our assay of cellular proliferation is found to correlate with DNA mismatch targeting by the bulky metallointercalators. It is the ⌬-isomer that is active both in targeting base mismatches and in inhibiting DNA synthesis. Additionally, the rhodium intercalators promote strand cleavage at the mismatch site with photoactivation, and we observe that the cellular response is enhanced with photoactivation. Targeting DNA mismatches may therefore provide a cell-selective strategy for chemotherapeutic design.DNA base mismatch ͉ metallointercalator

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“…It is the target of some anti-tumor reagents which reacts with DNA and stop its replication and inhibiting the growth of tumor cells [5] . By changing both the metal ions and the ligands, it is possible to modify the mode of interaction of the nucleic acids with the complexes [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization and DNA binding of copper(II) complexes with mixed ligands of 1, 10-phenanthroline / 2-2’ bipyridyl, L-methionine and ethylamine: Studies on antimicrobial and anti-cancer activities

Ezhilarasan¹,

Krishnan²,

Arumugham³

2017

Int. J. Curr. Res. Chem. Pharm. Sci

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Ternary copper(II) complexes [Cu(phen)(L-met)EA)] 1 & [Cu(Bpy)(L-met)EA] 2 ( phen = 1,10-phenanthroline Bpy = bipyridyl, LMethionine and EA= Ethylamine), have been synthesized and characterized by CHN analysis, molar conductance, electronic absorption, IR and EPR spectral studies. They have been tested for their in vitro DNA binding activities by the spectroscopic methods such as UV-Visible, Cyclic volumetric and viscosity measurement. Further, complexes 1 and 2 displayed significant cytotoxicity when examined in-vitro on a panel of cancerous cell line -human liver cancer cell line -HepG-2 cells (IC50= 40.82 and 29.74 μg/ml). Further complexes 1 & 2 were tested for their antimicrobial activities and it was found to have good antimicrobial activities.

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DNA photocleavage by phenanthrenequinone diimine complexes of rhodium(III): shape-selective recognition and reaction

Cited by 384 publications

References 1 publication

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

DNA mismatch-specific targeting and hypersensitivity of mismatch-repair-deficient cells to bulky rhodium(III) intercalators

Synthesis, characterization and DNA binding of copper(II) complexes with mixed ligands of 1, 10-phenanthroline / 2-2’ bipyridyl, L-methionine and ethylamine: Studies on antimicrobial and anti-cancer activities

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