The antimicrobial activity of inert oligonuclear polypyridylruthenium(II) complexes against pathogenic bacteria, including MRSA

The minimum inhibitory concentrations (MIC) of a series of synthetic inert polypyridylruthenium(II) complexes against four strains of bacteria--Gram positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa)--have been determined. The results demonstrate that for the dinuclear ruthenium(II) complexes ΔΔ/ΛΛ-[{Ru(phen)(2)}(2){μ-bb(n)}](4+) {where phen = 1,10-phenanthroline; bb(n) = bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane (n = 2, 5, 7, 10, 12 or 16)} the complexes linked by the bb(12), bb(14) and bb(16) ligands are highly active, with MIC values of 1 μg mL(-1) against both S. aureus and MRSA, and 2-4 and 8-16 μg mL(-1) against E. coli and P. aeruginosa, respectively. The mononuclear complex [Ru(Me(4)phen)(3)](2+) showed equal activity (on a mole basis) against S. aureus compared with the Rubb(12), Rubb(14) and Rubb(16), but was considerably less active against MRSA and the two Gram negative bacteria. For the dinuclear Rubb(n) family of complexes, the antimicrobial activity was related to the octanol-water partition coefficient (logP). However, the highly lipophilic mononuclear complex Δ-[Ru(phen)(2)(bb(16))](2+) was significantly less active than Rubb(16), highlighting the importance of the dinuclear structure. Preliminary toxicity assays were also carried out for the ΔΔ isomers of Rubb(7), Rubb(10), Rubb(12) and Rubb(16) against two human cells lines, fresh red blood cells and THP-1 cells. The results showed that the dinuclear ruthenium complexes are significantly less toxic to human cells compared to bacterial cells, with the HC(50) and IC(50) values 100-fold higher than the MIC for the complex that showed the best potential--ΔΔ-Rubb(12).     

Oligonuclear polypyridylruthenium(II) complexes incorporating flexible polar and non-polar bridges: synthesis, DNA-binding and cytotoxicity

The paper reports the synthesis and characterisation of a series of flexible di-bidentate bridging ligands in which two 4-methyl-2,2'-bipyridine groups are linked at the 4'-position by polymethylene (bb(n)), linear polyether (bbO(n)) or linear alkylamine (bbN(n)) chains of varying length (n). The enantiomers (ΔΔ/ΛΛ) of the rac forms of the ruthenium(ii) dinuclear complexes incorporating these ligands -i.e. [{Ru(phen)(2)}(2)(μ-BL)](4+) (phen = 1,10-phenanthroline; BL = bb(n), bbO(n) or bbN(n)) - have been isolated by reaction of Δ- or Λ-[Ru(phen)(2)(py)(2)](2+) (py = pyridine) with the respective bridging ligands. Mononuclear species - in which only one of the bidentate moieties of the bridging ligand is coordinated - have also been isolated, as well as trinuclear and tetranuclear species involving the bb(7) bridge. Fluorescence displacement studies of the DNA-binding of the dinuclear complexes containing the bbO(n) and bbN(n) bridges generally revealed a lower affinity than their bb(n) analogues for an oligonucleotide containing a single bulge site; the mononuclear complexes showed a lower affinity - and the trinuclear and tetranuclear complexes a higher affinity - than the dinuclear species, revealing an interesting interplay of lipophilicity, electrostatics and size in the complex/nucleic acid interaction. Cytotoxicity studies of these complexes against a murine leukaemia cell line revealed that the presence of the polyether or polyamine links in the chain lowered the cytotoxicity compared with their polymethylene analogues, and that the bb(7)-bridged trinuclear and tetranuclear complexes showed considerably enhanced cytotoxicity compared with the dinuclear Rubb(7) analogue.     

Dinuclear ruthenium(ii) complexes with flexible bridges as non-duplex DNA binding agents

The stereoisomers of a series of dinuclear ruthenium(ii) complexes [{Ru(phen)(2)}(2)(micro-BL)](4+) (phen = 1,10-phenanthroline) with flexible bridging ligands (BL) bb2 {1,2-bis[4(4'-methyl-2,2'-bipyridyl)]ethane}, bb5 {1,5-bis[4(4'-methyl-2,2'-bipyridyl)]pentane}, bb7 {1,7-bis[4(4'-methyl-2,2'-bipyridyl)]heptane}, and bb10 {1,10-bis[4(4'-methyl-2,2'-bipyridyl)]decane} have been synthesised. Their binding to a control dodecanucleotide, d(CCGGAATTCCGG)(2), and a tridecanucleotide, d(CCGAGAATTCCGG)(2), which contains a single adenine bulge have been studied using fluorescence displacement assays involving intercalating and groove-binding dyes, equilibrium dialysis and binding affinity chromatography. The fluorescence intercalator displacement (FID) assay indicated that LambdaLambda-[{Ru(phen)(2)}(2)(micro-bb7)](4+) had the greatest binding affinity with all the oligonucleotides, whereas an analogous fluorescence technique using a minor-groove binding dye, equilibrium dialysis and affinity binding chromatography showed that DeltaDelta-[{Ru(phen)(2)}(2)(micro-bb7)](4+) had the strongest binding. An (1)H NMR study of the binding of the DeltaDelta-enantiomer of [{Ru(phen)(2)}(2)(micro-bb7)](4+) to d(CCGAGAATTCCGG)(2) confirmed the selectivity of the metal complex for the bulge site and provided the basis for an energy-minimised binding model of the dinuclear ruthenium complex with the single adenine bulge containing trinucleotide. The binding model demonstrated the ability of the flexibly-linked complex to follow the curvature of the DNA minor groove.     

Monitoring the DNA binding kinetics of a binuclear ruthenium complex by energy transfer: evidence for slow shuffling

The semirigid binuclear ruthenium complex Delta,Delta-[mu-(11,11'-bidppz)(phen)(4)Ru(2)](4+) has been shown to rearrange slowly from an initial groove-bound nonluminescent state to a final intercalated emissive state by threading one of its bulky Ru(phen)(2) moieties through the DNA base stack. When this complex binds to poly[d(A-T)(2)], a further increase in emission from the complex is observed after completion of the intercalation, assigned to reorganization of the intercalated complex. We here report a study of the threading process in poly[d(A-T)(2)], in which the minor groove binding dye DAPI is used as an energy transfer probe molecule to assess the distribution of ruthenium complex during and also after the actual threading phase. The emission from DAPI is found to change with the same rate as the emission from the ruthenium complex, and furthermore, DAPI does not disturb the binding kinetics of the latter, justifying it as a good probe of both the threading and the reorganization processes. We conclude from the change in the emission from both DAPI and the ruthenium complex with time that DAPI-ruthenium interactions are most pronounced during the process of threading of the complex, suggesting that the complexes are initially threaded slightly anticooperatively and thereafter redistribute along the DNA to reach their thermodynamically most favorable distribution. The final distribution is characterized by a small but significant binding cooperativity, probably as a result of hydrophobic interactions between the complex ions despite their tetravalent positive charges. The mechanism of "shuffling" the complex along the DNA chain is discussed, i.e., whether the ruthenium complex remains threaded (requiring sequential base-pair openings) or if unthreading followed by lateral diffusion within the ionic atmosphere of the DNA and rethreading occurs.     

Charge separation in a ruthenium-quencher conjugate bound to DNA

A novel tris heteroleptic dipyridophenazine complex of ruthenium(II), [{Ru(phen)(dppz)(bpy'-his)}{Ru(NH3)5}]5+, containing a covalently tethered ruthenium pentammine quencher coordinated through a bridging histidine has been synthesized and characterized spectroscopically and biochemically in a DNA environment and in organic solvent. Steady-state and time-resolved luminescence measurements indicate that the tethered Ru complex is quenched relative to the parent complexes [Ru(phen)(dppz)(bpy')]2+ and [Ru(phen)(dppz)(bpy'-his)]2+ in DNA and acetonitrile, consistent with intramolecular photoinduced electron transfer. Intercalated into guanine-containing DNA, [{Ru(phen)(dppz)(bpy'-his)}{Ru(NH3)5}]5+, upon excitation and intramolecular quenching, is capable of injecting charge into the duplex based upon the EPR detection of guanine radicals. DNA-mediated charge transport is also indicated using a kinetically fast cyclopropylamine-substituted base as an electron hole trap. Guanine damage is not observed, however, in measurements using the guanine radical as the kinetically slower hole trap, indicating that back electron-transfer reactions are competitive with guanine oxidation. Moreover, transient absorption measurements reveal a novel photophysical reaction pathway for [{Ru(phen)(dppz)(bpy'-his)}{Ru(NH3)5}]5+ in the presence of DNA that is competitive with the intramolecular flash-quench process. These results illustrate the remarkably rich redox chemistry that can occur within a bimolecular ruthenium complex intercalated in duplex DNA.     

Characterization of the selective staining of DNA on gels using two fluorochromes

Ethidium bromide (EB) and 4'-6-diamidino-2-phenylindole (DAPI) are both well-known fluorochromes for detecting DNA fragments. EB binds to DNA by intercalation and DAPI binds in the DNA minor groove. We previously developed a staining method using both EB and DAPI that is selective for AT-rich DNA fragments. Using this double-staining method, AT-rich DNA fragments are visualized as bluish-white fluorescent bands. To further characterize this method, a series of synthetic DNA fragments were designed with systematic variations in the length, AT content, and DNA sequence pattern. The staining properties of these fragments were determined in the presence of DAPI and EB, and the following results were obtained. (i) In a series of fragments with three AT base pairs followed by one GC base pair, the stained DNA fragments exhibited different fluorescent colors and varied from bluish (more DAPI staining) to pinkish (less DAPI staining) in the order 5'-AAA-3', 5'-AAT-3', 5'-ATA-3', 5'-TTA-3'. (ii) In fragments with constant AT content, the blue fluorescent color increased with increasing number of A (or T) nucleotides, due to increased DAPI binding. The blue color was saturated when the number of A (or T) nucleotides was 12 or greater. (iii) The fluorescent color of the stained DNA fragments changed in the order of red-orange, pink, pinkish-white, white, bluish-white, blue as the AT content increased from 0 to 100%. Thus, the fluorescent color of DNA fragments stained with DAPI and EB depends on base composition and nucleotide sequence, suggesting that individual stained DNA fragments may have characteristic and specific fluorescent colors. The fluorescent color emitted by specific stained DNA fragments in the presence of EB and DAPI can be analyzed with a high degree of sensitivity and resolution using the XYZ colorimetric system.     

meso-[{Ru(phen)2}2(mu-HAT)]4+: a high-affinity DNA hairpin probe {HAT = 1,4,5,8,9,12-hexaazatriphenylene; phen = 1,10-phenanthroline}

1H NMR spectroscopy and fluorescent intercalator displacement (FID) assays have been used to investigate the DNA-binding abilities of two series of dinuclear polypyridyl ruthenium(II) complexes of the form [{Ru(L)2}2(mu-BL)]4+ {L = 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (Me2bpy), 1,10-phenanthroline (phen), or 4,7-dimethyl-1,10-phenanthroline (Me2phen); BL = 2,2'-bipyrimidine (bpm) or 1,4,5,8,9,12-hexaazatriphenylene (HAT)}. Preliminary FID surveys of these metal complexes against a variety of different oligonucleotides revealed that those complexes based upon the HAT bridging ligand induced greater fluorescence decreases in dye-bound DNA than did their bpm-bridged counterparts, suggesting a higher binding affinity by the HAT-bridged species. Furthermore, the greatest fluorescence decreases were typically observed in an oligonucleotide featuring a six-base hairpin loop. The apparent binding affinity of the metal complexes was also found to be a function of the stereochemistry and identity of the terminal ligands of the complex. The meso (DeltaLambda) stereoisomer generally induced greater fluorescence decreases than did either enantiomer (DeltaDelta or LambdaLambda), phen-based terminal ligands performed better than bpy-based terminal ligands, and those terminal ligands with methyl substituents demonstrated stronger apparent binding than did their non-methylated analogues. NMR experiments on meso-[{Ru(phen)2}2(mu-HAT)]4+ and meso-[{Ru(Me2phen)2}2(mu-HAT)]4+ demonstrated that both complexes bound with high affinity to the six-base hairpin oligonucleotide at the stem-loop interface and provided evidence to support stronger binding by the methylated species. meso-[{Ru(phen)2}2(mu-HAT)]4+ was found to bind poorly to duplex DNA and smaller four-base hairpin loops in FID and NMR experiments, whereas FID data suggest that the methylated analogue binds relatively strongly to most oligonucleotide sequences (the four- and six-base hairpins in particular). These results demonstrate that binding affinity can come at the expense of selectivity, with meso-[{Ru(phen)2}2(mu-HAT)]4+ proving to be an efficient compromise between the two as a high-affinity DNA hairpin probe.     

Synthesis, anticancer and antibacterial activity of some novel mononuclear Ru(II) complexes

In search of potential anticancer drug candidates in ruthenium complexes, a series of mononuclear ruthenium complexes of the type [Ru(phen)(2)(nmit)]Cl(2) (Ru1), [Ru(bpy)(2)(nmit)]Cl(2) (Ru2), [Ru(phen)(2)(icpl)]Cl(2) (Ru3), Ru(bpy)(2)(icpl)]Cl(2) (Ru4) (phen=1,10-phenanthroline; bpy=2,2'-bipyridine; nmit=N-methyl-isatin-3-thiosemicarbazone, icpl=isatin-3-(4-Cl-phenyl)thiosemicarbazone) and [Ru(phen)(2)(aze)]Cl(2) (Ru5), [Ru(bpy)(2)(aze)]Cl(2) (Ru6) (aze=acetazolamide) and [Ru(phen)(2)(R-tsc)](ClO(4))(2) (R=methyl (Ru7), ethyl (Ru8), cyclohexyl (Ru9), 4-Cl-phenyl (10), 4-Br-phenyl (Ru11), and 4-EtO-phenyl (Ru12), tsc=thiosemicarbazone) were prepared and characterized by elemental analysis, FTIR, (1)H-NMR and FAB-MS. Effect of these complexes on the growth of a transplantable murine tumor cell line (Ehrlich Ascites Carcinoma) and their antibacterial activity were studied. In cancer study the effect of hematological profile of the tumor hosts have also been studied. In the cancer study, the complexes Ru1-Ru4, Ru10 and Ru11 have remarkably decreased the tumor volume and viable ascitic cell count as indicated by trypan blue dye exclusion test (p<0.05). Treatment with the ruthenium complexes prolonged the lifespan of Ehrlich Ascites Carcinoma (EAC) bearing mice. Tumor inhibition by the ruthenium chelates was followed by improvements in hemoglobin, RBC and WBC values. All the complexes showed antibacterial activity, except Ru5 and Ru6. Thus, the results suggest that these ruthenium complexes have significant antitumor property and antibacterial activity. The results also reflect that the drug does not adversely affect the hematological profiles as compared to that of cisplatin on the host.     

DNA Interactions of a Dinuclear Ruthenium(II) Complex Bridged by 1,3-bis(1,10-phenanthroline[5,6-d]imidazol-2-yl)benzene

A novel dinuclear ruthenium(II) complex [(phen)₂Ru(mbpibH₂)Ru(phen)₂]⁴⁺ [phen = 1,10-phenanthroline; mbpibH₂ = 1,3-bis(1,10-phenanthroline[5,6-d]imidazol-2-yl)-benzene] has been synthesized and characterized. The DNA-binding behavior of this complex has been studied by spectroscopic and viscosity measurements. Results suggest that the dinuclear ruthenium(II) complex intercalates into DNA base pairs via its bridging moiety. It has also been found that the dinuclear ruthenium(II) complex displays the enantiopreferential DNA-binding after equilibrium dialysis.     

Ruthenium(II) [3 + 2 + 1] mixed ligand complexes: substituent effect on photolability, photooxidation of bases, photocytotoxicity and photonuclease activity

Mixed ligand complexes of ruthenium(II), [Ru(itpy)(bpy)Cl]ClO(4)1, [Ru(itpy)(phen)Cl]ClO(4)2, [Ru(bitpy)(bpy)Cl]ClO(4)3 and [Ru(bitpy)(phen)Cl]ClO(4)4 have been synthesized and characterized. Complex 3 has also been characterized crystallographically. These complexes exhibit photolability of the Ru-Cl bond. Upon irradiation at 440 nm in the presence of nucleosides and nucleotides the complexes exchange chloride for the nucleoside or nucleotide. The photolability of the Ru-Cl bond depends on the nature of the substituent in the tridentate tpy ligand. Photolysis of the complexes in the presence of a nucleoside or nucleotide also produces 8-oxoguanine due to the oxidation of guanine by the excited states of the complexes. These four complexes exhibit photonuclease properties and bring about the cleavage of plasmid DNA when irradiated at 440 nm. These complexes have been found to be toxic towards NIH 3T3 cells under photolytic conditions.     

新型双核配合物的形成、与DNA的作用机制及荧光性质研究

利用紫外、荧光和粘度等方法研究了含不同配体的钌(II)配合物[Ru(phen)₂CImP]^2＋(CImP＝3,4-二羟基-咪唑并[4,5-i][1,10]邻菲咯啉)和[Ru(phen)₂TPPZ]^2＋(TPPZ＝四吡啶[3,2-a:2',3'-c:3',2'-h:2',3'-j]吩嗪)与DNA的作用机制, 并研究了配合物与Zn^2＋配合后荧光性质变化. 结果表明[Ru(phen)₂TPPZ]^2＋与DNA以插入模式作用, 而[Ru(phen)₂CImP]^2＋与DNA则以沟面结合模式作用. 向配合物溶液中滴加Zn^2＋后, 配合物[Ru(phen)₂TPPZ]^2＋和[Ru(phen)₂CImP]^2＋均可以与Zn^2＋形成双核配合物[Ru(phen)₂(TPPZ)Zn]^4＋和[Ru(phen)₂(CImP)Zn]^4＋, 配合物的荧光减弱. 与DNA作用后, 配合物仍可以与Zn^2＋配位形成双核配合物, 但[Ru(phen)₂(TPPZ)Zn]^4＋保持插入模式与DNA作用, 配合物的荧光减弱. 而[Ru(phen)₂(CImP)Zn]^4＋与DNA则由沟面结合改为插入结合, 配合物的荧光增强.     

Exploring the interaction of ruthenium(II) polypyridyl complexes with DNA using single-molecule techniques

Here we explore DNA binding by a family of ruthenium(II) polypyridyl complexes using an atomic force microscope (AFM) and optical tweezers. We demonstrate using AFM that Ru(bpy)2dppz2+ intercalates into DNA (K(b) = 1.5 x 10(5) M(-1)), as does its close relative Ru(bpy)2dppx2+ (K(b) = 1.5 x 10(5) M(-1)). However, intercalation by Ru(phen)3(2+) and other Ru(II) complexes with K(b) values lower than that of Ru(bpy)2dppz2+ is difficult to determine using AFM because of competing aggregation and surface-binding phenomena. At the high Ru(II) concentrations required to evaluate intercalation, most of the DNA strands acquire a twisted, curled conformation that is impossible to measure accurately. The condensation of DNA on mica in the presence of polycations is well known, but it clearly precludes the accurate assessment by AFM of DNA intercalation by most Ru(II) complexes, though not by ethidium bromide and other monovalent intercalators. When stretching individual DNA molecules using optical tweezers, the same limitation on high metal concentration does not exist. Using optical tweezers, we show that Ru(phen)2dppz2+ intercalates avidly (K(b) = 3.2 x 10(6) M(-1)) whereas Ru(bpy)3(2+) does not intercalate, even at micromolar ruthenium concentrations. Ru(phen)3(2+) is shown to intercalate weakly (i.e., at micromolar concentrations (K(b) = 8.8 x 10(3) M(-1))). The distinct differences in DNA stretching behavior between Ru(phen)3(2+) and Ru(bpy)3(2+) clearly illustrate that intercalation can be distinguished from groove binding by pulling the DNA with optical tweezers. Our results demonstrate both the benefits and challenges of two single-molecule methods of exploring DNA binding and help to elucidate the mode of binding of Ru(phen)3(2+).     

Light-induced geometrical changes in acyclic ruthenium(II) complexes and their ruthena-macrocyclic analogues

The two ligands 1 (4'-(3-anisylphenyl)-2,2';6',2' '-terpyridine) and 2 (2-mesityl-8-anisyl-1,10-phenanthroline) (Scheme 2) were synthesized and coordinated to ruthenium. The corresponding complexes Ru(1)(2)(L)n+, where L = Cl-, CH3CN, or C5H5N, have been fully characterized. Notably, the hindering mesityl group of the phenanthroline ligand was shown to lie opposite to the monodentate ligand L both in solution and in the solid state. Upon irradiation in acetonitrile or pyridine, quantitative isomerization of the complex occurred, which consisted of a 90 degrees rotation of the bidentate chelate. In the new isomers the mesityl group was shown to pi stack to the coordinated monodentate ligand with the anisyl group of the phen (1,10-phenanthroline) lying on the other side of the ruthenium atom. The back reaction was performed by heating the photochemical isomers of the complexes in DMSO and exchanging the DMSO with chloride anion, acetonitrile, or pyridine. The stability of the ruthenium(II)-pyridine bond was used in order to inscribe the Ru(terpy)(phen) motif in a molecular ring. Functionalization of the ligands and subsequent cyclization reaction on the complex were performed on the two isomers of Ru(1)(2)(C5H5N)2+. Four macrocyclic complexes including the Ru(terpy)(phen)(py)n+ moiety were obtained and characterized. A (CH2)18 alkane chain or polyethylene glycol chain formed the flexible part of the ruthena-macrocycles. Upon visible light irradiation a dramatic geometrical changeover of the cyclic complex took place, which could be reversed thermally.     

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.     

1H NMR studies of nickel(II) complexes bound to oligonucleotides: a novel technique for distinguishing the binding locations of metal complexes in DNA

The selective paramagnetic relaxation of oligonucleotide proton resonances of d(GTCGAC)(2) and d(GTGCAC)(2) by Ni(phen)(2)(L)(2+) where L = dipyridophenazine (dppz), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), and phenanthrenequinone (phi) has been examined to obtain structural insight into the noncovalent binding of these metal complexes to DNA. In the oligonucleotide d(GTCGAC)(2), preferential broadening of the G1H8, G4H8, T2H6, and C3H6 proton resonances was observed with Ni(phen)(2)(dppz)(2+), Ni(phen)(2)(dpq)(2+), and Ni(phen)(2)(phi)(2+). In the case of the sequence d(GTGCAC)(2), where the central two bases are juxtaposed from the previous one, preferential broadening was observed instead for the A5H2 proton resonance. Thus, a subtle change in the sequence of the oligonucleotide can cause significant change in the binding location of the metal complex in the oligonucleotide. Owing to comparable changes for all metal complexes and sequences in broadening of the thymine methyl proton resonances, we attribute the switch in preferential broadening to a change in site location within the oligomer rather than to an alteration of groove location. Therefore, even for DNA-binding complexes of low sequence-specificity, distinct variations in binding as a function of sequence are apparent.     

High-dimensional architectures from the self-assembly of lanthanide ions with benzenedicarboxylates and 1,10-phenanthroline

Six new coordination polymers, [Eu(1,2-BDC)(1,2-HBDC)(phen)(H(2)O)](n) (1), [Eu(2)(1,3-BDC)(3)(phen)(2)(H(2)O)(2)](n).4nH(2)O (2), [Eu(1,4-BDC)(3/2)(phen)(H(2)O)](n) (3), [Yb(2)(1,2-BDC)(3)(phen)(H(2)O)(2)](n).3.5nH(2)O (4), [Yb(2)(1,3-BDC)(3)(phen)(1/2)](n) (5), and [Yb(2)(1,4-BDC)(3)(phen)(2)(H(2)O)](n) (6), were synthesized by hydrothermal reactions of lanthanide chlorides with three isomers of benzenedicarboxylic acid (H(2)BDC) and 1,10-phenanthroline (phen), and characterized by single-crystal X-ray diffraction. 1 has a 2-D herringbone architecture with a Z-shaped cavity. 2 and 5 have different 3-D networks, but both are formed by 1,3-BDC anions bridging metal centers (Eu or Yb) via carboxylate groups. 3 and 6 possess similar layer structures which are further constructed to form 3-D networks by hydrogen bonds and/or pi-pi aromatic interactions. 4 comprises 1-D chains that are further interlinked via hydrogen bonds, resulting in a 3-D network. In the three europium complexes, all the europium ions are eight-coordinated, while the coordination numbers of the ytterbium ions in other three-coordination polymers range from six to eight. Crystal data: for 1, monoclinic, space group P2(1)/c, with a = 12.565(6) A, b = 16.005(8) A, c = 12.891(6) A, beta = 102.173(8) degrees, and Z = 4; for 2, monoclinic, space group P2(1)/c, with a = 20.979(4) A, b = 11.5989(19) A, c = 20.810(3) A, beta = 110.391(3) degrees, and Z = 4; for 3, triclinic, space group P1, with a = 10.331(5) A, b = 10.887(5) A, c = 11.404(5) A, alpha = 107.660(7) degrees, beta = 91.787(7) degrees, gamma = 112.946(6) degrees, and Z = 2; for 4, triclinic, space group P1, with a = 11.517(5) A, b = 13.339(5) A, c = 13.595(6) A, alpha = 87.888(7) degrees, beta = 67.759(6) degrees, gamma = 68.070(6) degrees, and Z = 2; for 5, orthorhombic, space group C222(1), with a = 8.174(2) A, b = 24.497(7) A, c = 29.161(8) A, and Z = 8; for 6, triclinic, space group P1, with a = 10.349(3) A, b = 11.052(3) A, c = 19.431(6) A, alpha = 105.464(4) degrees, beta = 91.300(5) degrees, gamma = 93.655(5) degrees, and Z = 2. The magnetic properties of 1 and 4 were investigated. The photophysical properties of 1 were also studied.     

Ruthenium(II) complexes of 6,7-dicyanodipyridoquinoxaline: synthesis, luminescence studies, and DNA interaction

The hexaflurophosphate and chloride salts of a series of ruthenium(II) complexes incorporating a new dipyridophenazine-based ligand, dicnq (6,7-dicyanodipyrido[2,2-d:2',3'-f]quinoxaline), are synthesized in good-to-moderate yields. These mono ([Ru(phen)2(dicnq)]2+; phen = 1,10-phenanthroline), bis ([Ru(phen)(dicnq)2]2+), and tris ([Ru(dicnq)3]2+) complexes are fully characterized by elemental analysis, infrared, FAB-MS, 1H NMR, and cyclic voltammetric methods. Results of absorption titration and thermal denaturation studies reveal that these complexes are moderately strong binders of calf-thymus (CT) DNA, with their binding constants spanning the range (1-3) x 10(4) M-1. On the other hand, under the identical set of experimental conditions of light and drug dose, the DNA (pBR 322)-photocleavage abilities of these ruthenium(II) complexes follow the order [Ru(phen)2(dicnq)]2+ > [Ru(phen)(dicnq)2]2+ > [Ru(dicnq)3]2+, an order which is the same as that observed for their MLCT emission quantum yields. Steady-state emission studies carried out in nonaqueous solvents and in aqueous media with or without DNA reveal that while [Ru(dicnq)3]2+ is totally nonemissive under these solution conditions, both [Ru(phen)2(dicnq)]2+ and [Ru(phen)(dicnq)2]2+ are luminescent and function as "molecular light switches" for DNA. Successive addition of CT DNA to buffered aqueous solutions containing the latter two complexes results in an enhancement of the emission in each case, with the enhancement factors at saturation being approximately 16 and 8 for [Ru(phen)2(dicnq)]2+ and [Ru(phen)(dicnq)2]2+, respectively. These results are discussed in light of the relationship between the structure-specific deactivations of the MLCT excited states of these metallointercalators and the characteristic features of their DNA interactions, and attempts are made to compare and contrast their properties with those of analogous dipyridophenazine-based complexes, including the ones reported in the preceding paper.     

Racemic Tartrate/Malate Anions Combine with Racemic Complex Cations to Form Optically Active Ionic Crystals

Spontaneous resolution has attracted continuing attention in various research fields since Pasteur's work on the crystallization behavior of racemic tartrate. Here, a unique example of this phenomenon is reported, involving ionic crystals generated from racemic RR/SS- tartrate or R/S-malate and racemic ΔΔ/ΛΛ-[Ag₃Rh₂(2-aminoethanethiolato)₆]³⁺ (ΔΔ/ΛΛ-[ 1 ]³⁺) in water. RR- and SS-tartrate selectively recognize the ΛΛ and ΔΔ isomers of [ 1 ]³⁺ to produce ionic crystals of (ΛΛ-[ 1 ])₂(RR-tartrate)₃ and (ΔΔ-[ 1 ])₂(SS-tartrate)₃, respectively, which can undergo spontaneous resolution. While spontaneous resolution also occurs when using R/S-malate, R- and S-malate select the opposite isomers of [ 1 ]³⁺ to give ionic crystals of (ΔΔ-[ 1 ])₂(R-malate)₃ and (ΛΛ-[ 1 ])₂(S-malate)₃, respectively. In the presence of S-aspartate, (ΛΛ-[ 1 ])₂(R-tartrate)₃ and (ΔΔ-[ 1 ])₂(S-tartrate)₃ are preferentially crystallized from ΔΔ/ΛΛ-[ 1 ]³⁺ and RR/SS-tartrate at solution pH values of 6 and 10, respectively. This finding provides significant insight into the optical resolution of chemical species by spontaneous resolution and the origin of homochirality in nature.     

Different effects of a cotemplate and [(transition-metal)(1,10-phenanthroline)(m)]2+ (m = 1-3) complex cations on the self-assembly of a series of hybrid selenidostannates showing combined optical properties of organic and inorganic components

1,10-Phenanthroline (phen) and monoprotonated methylamine molecules were used as a novel cotemplate to direct the formation of a new inorganic-organic hybrid selenidostannate, (CH(3)NH(3))(4)(Sn(2)Se(6))·6phen (1); while the utilization of three types of transition-metal (TM) phen complex cations with the TM/phen ration of 1:1, 1:2, and 1:3 as structure directors affords {[Mn(phen)(2)](2)(μ(2)-Sn(2)Se(6))}·H(2)O (2a), {[Fe(phen)(2)](2)(μ(2)-Sn(2)Se(6))} (2b), {[Mn(phen)](2)(μ(4)-Sn(2)Se(6))}(n) (3), {[Mn(phen)(2)](Sn(2)Se(5))}(n) (4), and [Fe(phen)(3)](n)(Sn(3)Se(7))(n)·1.25nH(2)O (5). These compounds show diverse structures with the selenidostannate anions varying from discrete, μ(2)- and μ(4)- (Sn(2)Se(6))(4-) anions, to one-dimensional (1-D) (1)(∞)(Sn(2)Se(5)(2-)) anionic chains, and two-dimensional (2-D) extended (2)(∞)(Sn(3)Se(7)(2-)) anionic layers, demonstrating different structure-directing abilities of the cotemplate and the three types of TM phen complex cations. This work clearly indicates that the approach of modifying the number of the free coordination sites of unsaturated TM phen complex cations is very exciting as a way to synthesize novel hybrid chalcogenidometalates. Of particular interest, the present compounds exhibit interesting optical properties that reflect the combined effects of both photoluminescence-active organic components and semiconducting inorganic chalcogenidometalate anionic networks.     

Mesoporous silica nanoparticles-assisted ruthenium(Ⅱ) complexes for live cell staining

Ruthenium complexes which can bind to DNA via electrostatic and intercalation interactions producing strong luminescence have become ideal candidates for DNA staining. However, some of them such as Ru(phen)_3Cl_2 and Ru(phen)_2(dppz)Cl_2 could hardly cross the cellular membrane of live cells which limited their further interaction with DNA in live cells. To solve this problem, a potential approach is to find a proper vehicle for loading and delivery of these ruthenium complexes into live cells.Mesoporous silica nanoparticles(MSNs) with non-toxicity and good biocompatibility can be good candidates. More importantly,ruthenium complexes with positively charge could be loaded on negatively charged MSNs via electrostatic attractions to form MSNs-Ru hybrid. In vitro test demonstrated that MSNs had no side effects on the interactions between Ru complexes and DNA.Furthermore, it is found that the MSNs-Ru hybrid can enter into living human cervical cancer cells HeLa and stain the DNA while the corresponding ruthenium complexes alone could hardly cross the cellular membrane in the control experiment, demonstrating MSNs can be employed to be an efficient ruthenium complexes delivery nanomaterial for live cell staining.