Interaction of rac-[Cu(diimine)3]2+ and rac-[Zn(diimine)3]2+ complexes with CT DNA: effect of fluxional Cu(II) geometry on DNA binding, ligand-promoted exciton coupling and prominent DNA cleavage

The complexes [Cu(phen)(3)](ClO(4))(2) 1, [Cu(5,6-dmp)(3)](ClO(4))(2) 2, [Cu(dpq)(3)](ClO(4))(2) 3, [Zn(phen)(3)](ClO(4))(2) 4, [Zn(5,6-dmp)(3)](ClO(4))(2) 5 and [Zn(dpq)(3)](ClO(4))(2) 6, where phen = 1,10-phenanthroline, 5,6-dmp = 5,6-dimethyl-1,10-phenanthroline and dpq = dipyrido[3,2-d:2',3'-f]quinoxaline, have been isolated, characterized and their interaction with calf thymus DNA studied by using a host of physical methods. The X-ray crystal structures of rac-[Cu(5,6-dmp)(3)](ClO(4))(2) and rac-[Zn(5,6-dmp)(3)](ClO(4))(2) have been determined. While 2 possesses a regular elongated octahedral coordination geometry (REO), 5 possesses a distorted octahedral geometry. Absorption spectral titrations of the Cu(II) complexes with CT DNA reveal that the red-shift (12 nm) and DNA binding affinity of 3 (K(b), 7.5 x 10(4) M(-1)) are higher than those of 1 (red-shift, 6 nm; K(b), 9.6 x 10(3) M(-1)) indicating that the partial insertion of the extended phen ring of dpq ligand in between the DNA base pairs is deeper than that of phen ring. Also, 2 with a fluxional Cu(II) geometry interacts with DNA (K(b), 3.8 x 10(4) M(-1)) more strongly than 1 suggesting that the hydrophobic forces of interaction of 5,6 methyl groups on the phen ring is more pronounced than the partial intercalation of phen ring in the latter with a static geometry. The DNA binding affinity of 1 is lower than that of its Zn(ii) analogue 4, and, interestingly, the DNA binding affinity 2 of with a fluxional geometry is higher than that of its Zn(II) analogue 5 with a spherical geometry. It is remarkable that upon binding to DNA 3 shows an increase in viscosity higher than that the intercalator EthBr does, which is consistent with the above DNA binding affinities. The CD spectra show only one induced CD band on the characteristic positive band of CT DNA upon interaction with the phen (1,4) and dpq (3,6) complexes. In contrast, the 5,6-dmp complexes 2 and 5 bound to CT DNA show exciton-coupled biphasic CD signals with 2 showing CD signals more intense than 5. The Delta-enantiomer of rac-[Cu(5,6-dmp)(3)](2+) 2 binds specifically to the right-handed B-form of CT DNA at lower ionic strength (0.05 M NaCl) while the Lambda-enantiomer binds specifically to the left-handed Z-form of CT DNA generated by treating the B-form with 5 M NaCl. The complex 2 is stabilized in the higher oxidation state of Cu(II) more than its phen analogue 1 upon binding to DNA suggesting the involvement of electrostatic forces in DNA interaction of the former. In contrast, 3 bound to DNA is stabilized as Cu(I) rather than the Cu(II) oxidation state due to partial intercalative interaction of the dpq ligand. The efficiencies of the complexes to oxidatively cleave pUC19 DNA vary in the order, 3> 1 > 2 with 3 effecting 100% cleavage even at 10 microM complex concentration. However, interestingly, this order is reversed when the DNA cleavage is performed using H(2)O(2) as an activator and the highest cleavage efficiency of 2 is ascribed to its electrostatic interaction with the exterior phosphates of DNA.     

Interaction of rac-[M(diimine)3]2+ (M=Co, Ni) complexes with CT DNA: role of 5,6-dmp ligand on DNA binding and cleavage and cytotoxicity

The complexes [Co(diimine)(3)](ClO(4))(2)1-3 and [Ni(diimine)(3)](ClO(4))(2)4-6, where diimine = 1,10-phenanthroline (phen) (1,4), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) (2,5) and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (3,6), have been isolated, characterized and their interaction with CT DNA studied by using a host of physical methods. The X-ray crystal structures of rac-[Co(5,6-dmp)(3)](ClO(4))(2)2 and rac-[Ni(5,6-dmp)(3)](ClO(4))(2)5 have been determined and the isostructural and also isomorphous complex cations possess distorted octahedral coordination geometries. The absorption spectral titrations of the complexes with DNA reveal that the CT DNA binding affinity (K(b)) of the complexes varies as 3>2>1; 6>5>4. The Ni(II) complexes display DNA binding stronger than the corresponding Co(II) analogues, which is expected of their bigger sizes. The higher DNA binding affinity of 3 and 6 is due to the involvement in partial insertion of the extended phen ring in between the DNA base pairs. In contrast, 2 and 5 interact with DNA in the major groove through hydrophobic forces involving the methyl groups on the 5,6 positions of phen ring. An enhancement in relative viscosities of DNA upon binding to 1-6 is consistent with the DNA binding affinities. The CD spectral studies show only an induced CD band on the characteristic positive band of CT DNA for both the phen (1,4) complexes. In contrast, the 5,6-dmp (2,5) and dpq (3,6) complexes bound to CT DNA exhibit biphasic CD signals in place of the positive CD band and the negative helicity band disappears. This reveals that the complexes bind to DNA enantiopreferentially and effect changes in secondary structure of DNA. The CV and DPV responses indicate that the DNA-bound dpq complexes are stabilized in the lower oxidation state of Co(II) more than in the Co(III) oxidation state. The prominent DNA cleavage abilities of 1-3 observed in the presence of H(2)O(2) (200 μM) follows the order 2>1>3 with efficiencies of more than 90% even at 10 μM complex concentration. Interestingly, Ni(II) complexes 4-6 exhibit higher cytotoxicity (IC(50): 1, 28.0; 2, 15.0; 3, 20.0; 4, 8.0; 5, 2.0; 6, 2.0 μM at 48 h; IC(50): 1, 30.0; 2, 20.0; 3, 25.0; 4, 10.0; 5, 3.0; 6, 3.0 μM at 24 h) against human breast cancer (MCF 7) cell lines than the Co(II) complexes 1-3 as well as cisplatin in spite of their inability to cleave DNA. Also, the 5,6-dmp complex 5 shows cytotoxicity higher than the dpq complex 6 at 24 h incubation time and both 5 and 6 display apoptotic and necrotic modes of cell death.     

Synthesis and spectroscopic DNA binding studies of [Ru(phen)2(tbtc)]2+ and [Ru(2,9-dmp)2(tbtc)]2+

A new polypyridyl ligand tbtc (tbtc=4,5,9,14-tetraaza-benzo[b]triphenylene-11-carboxylic acid methyl ester) and its complexes [Ru(phen)2(tbtc)]2+ (1) (phen=1,10-phenanthroline) and [Ru(2,9-dmp)2(tbtc)]2+ (2) (2,9-dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by element analysis, MS, and 1H NMR. The DNA binding properties of both complexes to calf thymus DNA (CT-DNA) were investigated by different spectrophotometric methods and viscosity measurements. The results suggest that both complexes bind to DNA via an intercalative mode, and the DNA binding affinity of complex 1 is much greater than that of complex 2. This difference in binding affinity probably was caused by the different ancillary ligands. Also, when irradiated at 365 nm, complex 1 was found to be a more-effective DNA-cleaving agent than complex 2.     

Interaction studies of DNA binding of ruthenium(II) mixed-ligand complexes: [Ru(phen)2(dtmi)]2+ and [Ru(phen)2(dtni)]2+

Two new ligands, 3-(pyrazin-2-yl)-as-triazino[5,6-f]-5-methoxylisatin (dtmi), 3-(pyrazin-2-yl)-as-triazino[5,6-f]-5-nitroisatin (dtni) and their ruthenium(II) complexes [Ru(phen)2(dtmi)](ClO4)2 (1) and [Ru(phen)2(dtni)](ClO4)2 (2) have been prepared and characterized by elemental analysis, FAB-MS, ES-MS and 1H NMR. The DNA-binding behaviors of complexes have been studied by spectroscopic titration, viscosity measurements, thermal denaturation and circular dichromism (CD). The results indicate that the complexes 1 and 2 interact with calf thymus DNA (CT-DNA) by intercalative mode. The DNA-binding affinity of the complexes 2 is larger than that complex 1 does.     

Synthesis,characterization and DNA binding and photocleavage studies of [Ru(bpy)2BDPPZ]2+, [Ru(dmb)2BDPPZ]2+ and [Ru(phen)2BDPPZ]2+ complexes and their antimicrobial activity

Polypyridyl ligand 9a,13a‐dihydro‐4,5,9,14‐tetraaza‐benzo[b]triphenylene‐11‐yl)‐phenyl‐methanone (BDPPZ) and its complexes [Ru(bpy)₂BDPPZ]²⁺, [Ru(dmb)₂BDPPZ]²⁺ and [Ru(phen)₂BDPPZ]²⁺ (where bpy = 2,2′‐bipyridine, dmb = 4,4′‐dimethyl‐2,2′‐bipyridine, phen = 1,10‐phenanthroline) have been synthesized and characterized by elemental analysis, IR, UV–vis, ¹H‐NMR, ¹³C‐NMR and mass spectra. The DNA‐binding properties of the complexes were investigated by absorption, emission, melting temperature and viscosity measurements. Experimental results indicate that the three complexes can intercalate into DNA base pairs. Photo activated cleavage of pBR‐322 DNA by the three complexes was also studied. Further, all three Ru(II) complexes synthesized were screened for their antimicrobial activity. Copyright © 2009 John Wiley & Sons, Ltd.     

Photoinitiated DNA Binding by cis-[Ru(bpy)2(NH3)2]2+

The ligand-loss photochemistry of cis-[Ru(bpy)(2)(NH(3))(2)](2+) (bpy = 2,2'-bipyridine) was investigated in water and in the presence of added ligands such as bipyridine and chloride. Irradiation of the complex results in the covalent binding to 9-methyl- and 9-ethylguanine, as well as to single-stranded and double-stranded DNA. This photoinduced DNA binding is not observed for the control complex [Ru(bpy)(2)(en)](2+) (en = ethylenediamine) under similar irradiation conditions. The results presented here show that octahedral Ru(II) complexes with photolabile ligands may prove useful as photoactivated cisplatin analogs.     

Catalytic enantiospecific [3+2] annulation of aminocyclopropanes with ketones

An almost familiar ring: The first enantiospecific [3+2] annulation of donor-acceptor aminocyclopropanes with ketones is reported (see scheme; Phth=phthaloyl). The reaction is catalysed by tin(IV) chloride (5?mol?%) at -78?°C and gives aminotetrahydrofurans bearing a quaternary C5 atom in high yield, diastereoselectivity and enantiospecificity (see scheme).     

Enantioselective luminescence quenching of DNA light-switch [Ru(phen)2dppz]2+ by electron transfer to structural homologue [Ru(phendione)2dppz]2+

The quenching of the luminescence of [Ru(phen)(2)dppz](2+) by structural homologue [Ru(phendione)(2)dppz](2+), when both complexes are bound to DNA, has been studied for all four combinations of Delta and Lambda enantiomers. Flow linear dichroism spectroscopy (LD) indicates similar binding geometries for all the four compounds, with the dppz ligand fully intercalated between the DNA base pairs. A difference in the LD spectrum observed for the lowest-energy MLCT transition suggests that a transition, potentially related to the final localization of the excited electron to the dppz ligand in [Ru(phen)(2)dppz](2+), is overlaid by an orthogonally polarized transition in [Ru(phendione)(2)dppz](2+). This would be consistent with a low-lying LUMO of the phendione moiety of [Ru(phendione)(2)dppz](2+) that can accept the excited electron from [Ru(phen)(2)dppz](2+), thereby quenching the emission of the latter. The lifetime of excited Delta-[Ru(phen)(2)dppz](2+) is decreased moderately, from 664 to 427 ns, when bound simultaneously with the phendione complex to DNA. The 108 ns lifetime of opposite enantiomer, Lambda-[Ru(phen)(2)dppz](2+), is only shortened to 94 ns. These results are consistent with an average rate constant for electron transfer of approximately 1.10(6) s(-1) between the phenanthroline- and phendione-ruthenium complexes. At binding ratios close to saturation of DNA, the total emission of the two enantiomers is lowered equally much, but for the Lambda enantiomer, this is not paralleled by a decrease in luminescence lifetime. A binding isotherm simulation based on a generalized McGhee-von Hippel approach shows that the Delta enantiomer binds approximately 3 times stronger to DNA both for [Ru(phendione)(2)dppz](2+) and [Ru(phen)(2)dppz](2+). This explains the similar decrease in total emission, without the parallel decrease in lifetime for the Lambda enantiomer. The simulation also does not indicate any significant binding cooperativity, in contrast to the case when Delta-[Rh(phi)(2)bipy](3+) is used as quencher. The very slow electron transfer from [Ru(phen)(2)dppz](2+) to [Ru(phendione)(2)dppz](2+), compared to the case when [Rh(phi)(2)phen](3+) is the acceptor, can be explained by a much smaller driving free-energy difference.     

Effect of the ancillary ligands on the binding of ruthenium(II) complexes [Ru(dmp)2(MCMIP)]2+ and [Ru(dmb)2(MCMIP)]2+ with DNA

Two polypyridine ruthenium(II) complexes, [Ru(dmp)₂(MCMIP)]²⁺ (1) (MCMIP = 2-(6-methyl-3-chromonyl)imidazo[4,5-f][1,10]-phenanthroline, dmp = 2,9-dimethyl-1,10-phenanthroline) and [Ru(dmb)₂(MCMIP)]²⁺ (2) (dmb = 4,4′-dimethyl-2,2′-bipyridine), have been synthesized and characterized by elemental analysis, ES-MS and ¹H NMR. The DNA-binding behaviors of these complexes were investigated by electronic absorption titration, fluorescence spectroscopy, viscosity measurements and thermal denaturation. The results show that 1 and 2 effectively bind to CT-DNA; the DNA-binding affinities are closely related to the ancillary ligand.     

Templated synthesis of a rotaxane with a [Ru(diimine)3]2+ core

A rotaxane containing a ruthenium bisphenanthroline complex, acting as an axis, and a macrocycle incorporating a 2,2'-bipyridine (bpy) unit, threaded by the axis, has been synthesized. The bisphenanthroline ligand is such that its ruthenium(II) complexes possess a clearly identified axis, making such compounds ideal components of rotaxanes constructed around an octahedral ruthenium(II) center, which serves as a template. The ring is threaded by the axial ruthenium(II) precursor complex, to afford the corresponding pseudorotaxane in moderate yield. The X-ray structure analysis of this compound reveals the threaded nature of the complex. The length of the threaded ring (35 atoms in the periphery) is too short to allow easy threading of the axis through the macrocycle. As a consequence, an isomer is also obtained for which the axial ruthenium complex is attached in an exo fashion. (1)H NMR studies have been carried out, which reveal various conformational equilibria for the pseudorotaxane. Light-induced decoordination of the bpy-containing cyclic fragment was shown to be quantitative and to lead to the free ring and the axial ruthenium(II) complex, regardless of the starting compound (pseudorotaxane or exo isomer). Finally, the real rotaxane could be prepared, although it could not be separated from its exo isomer.     

Mesoscale DNA structural changes on binding and photoreaction with Ru[(TAP)2PHEHAT]2+

We used scanning force microscopy (SFM) to study the binding and excited state reactions of the intercalating photoreagent Ru[(TAP)(2)PHEHAT](2+) (TAP = 1,4,5,8-tetraazaphenanthrene; PHEHAT = 1,10-phenanthrolino[5,6-b]1,4,5,8,9,12-hexaazatriphenylene) with DNA. In the ground state, this ruthenium complex combines a strong intercalative binding mode via the PHEHAT ligand, with TAP-mediated hydrogen bonding capabilities. After visible irradiation, SFM imaging of the photoproducts revealed both the structural implications of photocleavages and photoadduct formation. It is found that the rate of photocleaving is strongly increased when the complex can interact with DNA via hydrogen bonding. We demonstrated that the photoadduct increases DNA rigidity, and that the photo-biadduct can crosslink two separate DNA segments in supercoiled DNA. These mechanical and topological effects might have important implications in future therapeutic applications of this type of compounds.     

Base-Modified DNA Labeled by [Ru(bpy)3]2+ and [Os(bpy)3]2+ Complexes: Construction by Polymerase Incorporation of Modified Nucleoside Triphosphates,Electrochemical and Luminescent Properties,and Applications

Modified 2′-deoxynucleoside triphosphates (dNTPs) bearing [Ru(bpy)₃]²⁺ and [Os(bpy)₃]²⁺ complexes attached via an acetylene linker to the 5-position of pyrimidines (C and U) or to the 7-position of 7-deazapurines (7-deaza-A and 7-deaza-G) have been prepared in one step by aqueous cross-couplings of halogenated dNTPs with the corresponding terminal acetylenes. Polymerase incorporation by primer extension using Vent (exo-) or Pwo polymerases gave DNA labeled in specific positions with Ru²⁺ or Os²⁺ complexes. Square-wave voltammetry could be efficiently used to detect these labeled nucleic acids by reversible oxidations of Ru^2+/3+ or Os^2+/3+. The redox potentials of the Ru²⁺ complexes (1.1–1.25 V) are very close to that of G oxidation (1.1 V), while the potentials of Os²⁺ complexes (0.75 V) are sufficiently different to enable their independent detection. On the other hand, Ru²⁺-labeled DNA can be independently analyzed by luminescence. In combination with previously reported dNTPs bearing ferrocene, aminophenyl, and nitrophenyl tags, the Os-labeled dATP has been successfully used for “multicolor” redox labeling of DNA and for DNA minisequencing.     

Synthesis of C-arylglycosides via Ru(II)-catalyzed [2 + 2 + 2] cycloaddition

In the presence of catalytic amounts of Cp*RuCl(cod), the cycloaddition of 1,6-diynes with various C-alkynylglycosides proceeded at ambient temperature to afford C-arylglycosides in 46-93% yields.     

Tuning and switching MLCT phosphorescence of [Ru(bpy)3]2+ complexes with triarylboranes and anions

Four new Ru(II) complexes, [Ru(bpy)(2)(4,4'-BP2bpy)][PF(6)](2) (1), [Ru(t-Bu-bpy)(2)(4,4'-BP2bpy)][PF(6)](2) (2), [Ru(bpy)(2)(5,5'-BP2bpy)][PF(6)](2) (3), and [Ru(t-Bu-bpy)(2)(5,5'-BP2bpy)][PF(6)](2) (4) have been synthesized (where 4,4'-BP2bpy = 4,4'-bis(BMes(2)phenyl)-2,2'-bpy; 5,5'-BP2bpy = 5,5'-bis(BMes(2)phenyl)-2,2'-bpy (4,4'-BP2bpy); and t-Bu-bpy = 4,4'-bis(t-butyl)-2,2'-bipyridine). These new complexes have been fully characterized. The crystal structures of 3 and 4 were determined by single-crystal X-ray diffraction analyses. All four complexes display distinct metal-to-ligand charge transfer (MLCT) phosphorescence that has a similar quantum efficiency as that of [Ru(bpy)(3)][PF(6)](2) under air, but is at a much lower energy. The MLCT phosphorescence of these complexes has been found to be highly sensitive toward anions such as fluoride and cyanide, which switch the MLCT band to higher energy when added. The triarylboron groups in these compounds not only introduce this color switching mechanism, but also play a key role in the phosphorescence color of the complexes.     

[Ru(bpy)2L]2+、[Ru(phen)2L]2+(L=pytp,pztp)电子结构与抗癌活性研究

Theoretical studies on the complexes Ru(bpy)2L2+, Ru(phen)2L2+ (L=pytp,pztp) were carried out by using the density functional theory (DFT) method at B3LYP/LanL2DZ level. The relation between electronic structures and anti-cancer activities of complexes was investigated. The increasing of N in the main ligand can strengthen the interaction of complexes with DNA and anti cancer activities of complexes. The calculation results show that for complexes I-IV, their energies of LUMO orbital are in the order of εI>εII, εIII>εIV, the electron cloud components of LUMO come mainly from main ligands and the content distributing is in the order of I相似文献   

Selective binding of cucurbit[7]uril and beta-cyclodextrin with a redox-active molecular triad Ru(bpy)(3)-MV2+ -naphthol

A 1ratio1ratio1 inclusion complex is formed by the binding interactions among beta-CD, CB[7] hosts, and Ru(bpy)(3)-terminated viologen-naphthalene guest in aqueous solution, in which the positions of both CB[7] and beta-CD are closer to the Ru stopper than in the respective 1ratio1 inclusion complexes, forming a "tightened nut on bolt" structural mode.