Structure determination of an intercalating ruthenium dipyridophenazine complex which kinks DNA by semiintercalation of a tetraazaphenanthrene ligand (original) (raw)
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Angewandte Chemie, 2019
Using X-ray crystallography, we show an enantiospecificity in DNA G-quadruplex binding, using the complexes Λ/∆-[Ru(TAP)2(dppz-11-CN)] 2+ (TAP=1,4,5,8tetraazaphenanthrene) containing the dppz (dipyridophenazine) ligand, paralleling the specificity of the complexes with duplex DNA. The Λ complex crystallises with the normally parallel stranded d(TAGGGTTA) tetraplex to give the first such antiparallel strand assembly in which syn-guanosine is adjacent to the complex at the 5' end of the quadruplex core. SRCD measurements confirm that the same conformational switch occurs in solution. The Δ enantiomer, by contrast, is present in the structure but stacked at the ends of the assembly. In addition, we report the structure of Λ-[Ru(phen)2(11-CN-dppz)] 2+ bound to d(TCGGCGCCGA), a duplex forming sequence, and use both structural models to aid in the elucidation of the motif-specific luminescence response of the isostructural phen analogue enantiomers.
Metal-based Drugs, 2001
The complexes [Ru ([9]aneS3)(dppz)Cl]Cl 1 and [Ru(II2]aneS4)(dppz)]Ci_ 2 ([9]aneS3=l,4,7 trithiaciclononane and [12]aneS4=l,4,7,10-tetrathiaciclododecane) were synthesised and fully characterised. These complexes belong to a small family of dipyridophenazine complexes with non-polypyridyl ancillary ligands. Interaction studies of these complexes with CT-DNA (UV/Vis titrations, steady-state emission and thermal denaturation) revealed their high affinity for DNA. Intercalation constants determined by UV/Vis titrations are of the same order of magnitude (106) as other dppz metallointercalators, namely [Ru(II)(bpy)2dppz]2+. Differences between and 2 were identified by steady-state emission and thermal denaturation studies. Emission results are in accordance with structural data, which indicate how geometric distortions and different donor and/or acceptor ligand abilities affect luminescence. The possibility of noncovalent interactions between ancillary ligands and nucleobases by van der Waals contacts and H-bridges is discussed. Furthermore, complex undergoes aquation under intra-cellular conditions and an equilibrium with the aquated form I' is attained. This behaviour may increase the diversity of available interaction modes.
Journal of Molecular Structure, 2001
Nanosecond transient resonance Raman and picosecond transient absorption spectroscopic investigations of the two structurally analogous Ru-polypyridyl complexes, Ruphen 2 dppz 21 (1) and Rutap 2 dppz 21 (2), are presented (phen 1,10phenanthroline, dppz dipyrido [3,2-a:2 0 ,3 0 -c] phenazine; tap 1,4,5,8 tetraazaphenanthrene). The ®ndings offer insight into the differing nature of the lowest excited states of the two complexes, and describe the role of these states within the very distinct photophysical behaviour of each, both in relation to solvent response and their interaction with DNA (facilitated in each case through the intercalating dppz ligand). The active, solvent-sensitive, dppz-based 3 MLCT states involved in the`lightswitch' behaviour of (1) are probed, alongside evidence of a progression through a precursor transient state when the complex is in non-aqueous environment. Evidence has been provided of a photophysical pathway for (2), involving formation of a tapbased lowest 3 MLCT state. When (2) is bound to DNA through the dppz ligand, a photo-driven electron transfer process ensues between the guanine base of DNA and the lowest 3 MLCT state. q
Inorganica Chimica Acta, 2011
In our search for new DNA intercalating ligands, a novel bifunctional intercalator 11-(9-acridinyl)dipyrido[3,2-a:2 0 ,3 0 -c]phenazine, acdppz (has two potentially effective intercalators via dipyridophenazine(dppz) and acridine which are linked together via C-C bond) and its corresponding Ru(II) polypyridyl complex [Ru(phen) 2 (acdppz)] 2+ (where phen = 1,10-phenanthroline) have been synthesized and characterized. The electrochemical behaviors of the ligand and its complex have been thoroughly examined. The structure of acdppz and [Ru(phen) 2 (acdppz)] 2+ were determined by X-ray crystallography. From the crystal structure of the complex, we found that the dppz moiety is not coplanar with the acridine ring, having a dihedral angle of 64.79 in the acdppz. The selected bond lengths and angles for the crystal structure of [Ru(phen) 2 (acdppz)] 2+ were compared to the geometry-optimized molecular structure of [Ru(phen) 2 (acdppz)] 2+ derived by Gaussian. The interaction of [Ru(phen) 2 (acdppz)] 2+ with calfthymus (CT) DNA was investigated by absorption and viscometry titration, thermal denaturation studies. The above measurements indicated that the complex binds less strongly with the CT DNA due to the intercalation by the ruthenium bound acdppz with an intrinsic binding constant of 2.6 Â 10 5 M À1 . Molecular-modeling studies also support an intercalative mode of binding of the complex to the model duplex d(CGCAATTGCG) 2 possibly from the major groove with a slight preference for GC rich region. Additionally, the title complex promotes the cleavage of plasmid pBR322 DNA upon irradiation under aerobic conditions.
Ruthenium(II) Complexes of Bipyridine−Glycoluril and their Interactions with DNA
Bioconjugate Chemistry, 2009
Nine complexes of the type [Ru(N-N) 2 (BPG)]Cl 2 1-4, [Ru(N-N)(BPG) 2 ]Cl 2 5-8, and [Ru(BPG) 3 ]Cl 2 9 where N-N is 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido [3,2-d:2′,3′-f]quinoxaline (dpq), dipyrido[3,2a:2′,3′-c]phenazine (dppz), which incorporates bipyridine-glycoluril 5,[1,10]phenanthroline-6,13-dione) as the ancillary ligand, have been synthesized and characterized. These complexes with the peripheral polypyridyl ligands have the ability to form conjugates with DNA. The DNA binding (absorption spectroscopy, steady-state and time-resolved emission measurements, steady-state emission quenching measurements) and cleavage (under dark and irradiated conditions) by these complexes has been studied to investigate the influence of the ancillary ligand. The binding ability of these complexes to DNA is dependent on the planarity of the intercalative polypyridyl ligand, which is further affected by the ancillary bipyridine-glycoluril ligand. The complexes 3, 4, 7, and 8 bind to CT-DNA with binding constants on the order of 10 4 M -1 . Time-resolved emission measurements on the DNA-bound complexes 1, 3, 5-7, and 9 show monoexponential decay of the excited states, whereas complexes 2, 4, and 8 show biexponential decay with short-and long-lived components. Interaction of complexes 2-9 with plasmid pBR322 DNA studied by gel electrophoresis experiments reveals that all complexes cleave DNA efficiently at micromolar concentrations under dark and anaerobic conditions probably by a hydrolytic mechanism. Complexes 3, 4, 7, 8, and [Ru(bpy) 2 (dppz)] 2+ show extensive DNA cleavage in the presence of light with a shift in mobility of form I of DNA probably due to the high molecular weight of DNA-complex conjugates. However, the extent of the cleavage is augmented on irradiation in the case of complexes 3, 4, 7, and 8, which include the planar dpq and dppz ligands, suggesting a combination of hydrolytic and oxidative mechanism for the DNA scission. Molecular mechanics calculations of these systems corroborate the DNA binding and cleavage mechanisms. *
Journal of Inorganic Biochemistry, 2008
The interaction of enantiomerically pure dinuclear complexes of the form [Ru 2 (L-L) 4 L 1 ] 4+ (where L-L = 2,2 0-bipyridine (bpy) or 1,10-phenanthroline (phen) and L 1 = bis(pyridylimine) ligand ((C 5 H 4 N)C@ N(C 6 H 4)) 2 CH 2)) with ct-DNA have been investigated by absorbance, circular dichroism, fluorescence displacement assays, thermal analysis, linear dichroism and gel electrophoresis. The complexes all bind more strongly to DNA than ethidium bromide, stabilise DNA and have a significant bending effect on DNA. The data for D,D-[Ru 2 (bpy) 4 L 1 ] 4+ are consistent with it binding to DNA outside the grooves wrapping the DNA about it. By way of contrast the other complexes are groove-binders. The phen complexes provide a chemically and enantiomerically stable alternative to the DNA-coiling di-iron triple-helical cylinder previously studied. In contrast to the di-iron helicates, the phen complexes show DNA sequence effects with D,D-[Ru 2 (phen) 4 L 1 ] 4+ binding preferentially to GC and K,K-[Ru 2 (phen) 4 L 1 ] 4+ to AT.
Chemical Communications, 1996
Resonance Raman (RR) spectroscopy has been used to probe the interaction between dipyridophenazine (dppz) complexes of ruthenium(II), [Ru(L) 2 (dppz)] 2+ (L) 1,10-phenanthroline (1) and 2,2-bipyridyl (2)), and calfthymus DNA. Ground electronic state RR spectra at selected probe wavelengths reveal enhancement patterns which reflect perturbation of the dppz-centered electronic transitions in the UV-vis spectra in the presence of DNA. Comparison of the RR spectra recorded of the short-lived MLCT excited states of both complexes in aqueous solution with those of the longer-lived states of the complexes in the DNA environment reveals changes to excited state modes, suggesting perturbation of electronic transitions of the dppz ligand in the excited state as a result of intercalation. The most prominent feature, at 1526 cm-1 , appears in the spectra of both 1 and 2 and is a convenient marker band for intercalation. For 1, the excited state studies have been extended to the ∆ and Λ enantiomers. The marker band appears at the same frequency for both but with different relative intensities. This is interpreted as reflecting the distinctive response of the enantiomers to the chiral environment of the DNA binding sites. The results, together with some analogous data for other potentially intercalating complexes, are considered in relation to the more general application of time-resolved RR spectroscopy for investigation of intercalative interactions of photoexcited metal complexes with DNA.