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Research has been conducted on the ligand-bridged bimetallic complexes containing [RuCl-([9]aneS (sub)3)] (super)+ metal centers. The electron transfer and chemical properties of these complexes have been investigated and the results indicate that the complexes display intense bimetallic interactions.

The synthesis and characterization of monocationic and dicationic achiral [Ru.sub.II] complexes based on dipyrido[3,3-a:2',3'-c]phenazine) (dppz) and benzo[i]dipyrido-[3,2-a:2',3'-c]phenazine) (dppn) ligands is presented. Their photophysical and DNA binding properties are found to be dependent on the nature of the ligand and cationic charge.

The synthesis of dinuclear [Ru(super II)([n]aneS(sub 4))] (where n = 12, 14) complexes of the bridging ligand 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine is reported. A comparison of the electrochemistry of the three complexes reveals that the first oxidation of the [Ru(super II)([n]aneS(sub 4))]-based systems is a ligand-based couple, indicating that the formation of the radical anion form of the bridging ligand is stabilized by metal center coordination.

The synthesis of a water-soluble derivative of dipyrido[3,2-a:2',3'-c]phenazine 9dppz) is reported. The structure of this compound is obtained by X-ray crystallography.

An easy modular strategy is outlined to synthesize the dinuclear systems, which contain tethered achiral units. A study done on preliminary DNA binding of a prototypical system is discussed.

Increasing concern over rising levels of antibiotic resistance among pathogenic bacteria has prompted significant research into developing efficacious alternatives to antibiotic treatment. Previously, we have reported on the therapeutic activity of a dinuclear ruthenium(II) complex against pathogenic, multi-drug-resistant bacterial pathogens. Herein, we report that the solubility properties of this lead are comparable to those exhibited by orally available therapeutics that in comparison to clinically relevant antibiotics it induces very slow evolution of resistance in the uropathogenic, therapeutically resistant, E. coli strain EC958, and this resistance was lost when exposure to the compound was temporarily removed. With the aim of further investigating the mechanism of action of this compound, the regulation of nine target genes relating to the membrane, DNA damage, and other stress responses provoked by exposure to the compound was also studied. This analysis confirmed that the compound causes a significant transcriptional downregulation of genes involved in membrane transport and the tricarboxylic acid cycle. By contrast, expression of the chaperone protein-coding gene, spy , was significantly increased suggesting a requirement for repair of damaged proteins in the region of the outer membrane. The complex was also found to display activity comparable to that in E. coli in a range of other therapeutically relevant Gram-negative pathogens., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

The synthesis of new dinuclear complexes containing linked Ru II (dppz) and Re I (dppz) moieties is reported. The photophysical and biological properties of the new complex, which incorporates a N , N '-bis(4-pyridylmethyl)-1,6-hexanediamine tether ligand, are compared to a previously reported Ru II /Re I complex linked by a simple dipyridyl alkane ligand. Although both complexes bind to DNA with similar affinities, steady-state and time-resolved photophysical studies reveal that the nature of the linker affects the excited state dynamics of the complexes and their DNA photocleavage properties. Quantum-based DFT calculations on these systems offer insights into these effects. While both complexes are live cells permeant, their intracellular localizations are significantly affected by the nature of the linker. Notably, one of the complexes displayed concentration-dependent localization and possesses photophysical properties that are compatible with SIM and STED nanoscopy. This allowed the dynamics of its intracellular localization to be tracked at super resolutions.

Over the past 10 years, polyvalent DNA-gold nanoparticle (DNA-GNP) conjugate has been demonstrated as an efficient, universal nanocarrier for drug and gene delivery with high uptake by over 50 different types of primary and cancer cell lines. A barrier limiting its in vivo effectiveness is limited resistance to nuclease degradation and nonspecific interaction with blood serum contents. Herein we show that terminal PEGylation of the complementary DNA strand hybridized to a polyvalent DNA-GNP conjugate can eliminate nonspecific adsorption of serum proteins and greatly increases its resistance against DNase I-based degradation. The PEGylated DNA-GNP conjugate still retains a high cell uptake property, making it an attractive intracellular delivery nanocarrier for DNA binding reagents. We show that it can be used for successful intracellular delivery of doxorubicin, a widely used clinical cancer chemotherapeutic drug. Moreover, it can be used for efficient delivery of some cell-membrane-impermeable reagents such as propidium iodide (a DNA intercalating fluorescent dye currently limited to the use of staining dead cells only) and a diruthenium complex (a DNA groove binder), for successful staining of live cells.

We report DNA binding studies of the dinuclear ruthenium ligand [{Ru(phen)2}2tpphz](4+) in enantiomerically pure forms. As expected from previous studies of related complexes, both isomers bind with similar affinity to B-DNA and have enhanced luminescence. However, when tested against the G-quadruplex from human telomeres (which we show to form an antiparallel basket structure with a diagonal loop across one end), the ΛΛ isomer binds approximately 40 times more tightly than the ΔΔ, with a stronger luminescence. NMR studies show that the complex binds at both ends of the quadruplex. Modeling studies, based on experimentally derived restraints obtained for the closely related [{Ru(bipy)2}2tpphz](4+), show that the ΛΛ isomer fits neatly under the diagonal loop, whereas the ΔΔ isomer is unable to bind here and binds at the lateral loop end. Molecular dynamics simulations show that the ΔΔ isomer is prevented from binding under the diagonal loop by the rigidity of the loop. We thus present a novel enantioselective binding substrate for antiparallel basket G-quadruplexes, with features that make it a useful tool for quadruplex studies.

The synthesis of dinuclear [Ru(II)([n]aneS(4))] (where n = 12, 14) complexes of the bridging ligand 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine are reported. The X-ray structures of both of the new complexes are compared to a newly obtained structure for a dinuclear [Ru(II)([9]aneS(3))]-based analogue, whose synthesis has previously been reported. A comparison of the electrochemistry of the three complexes reveals that the first oxidation of the [Ru(II)([n]aneS(4))]-based systems is a ligand-based couple, indicating that the formation of the radical anion form of the bridging ligand is stabilized by metal center coordination. Spectroelectrochemistry studies on the mixed-valence form of the new complexes suggest that they are Robin and Day Class II systems. The electrochemical and electronic properties of these complexes is rationalized by a consideration of the pi-bonding properties of thiacrown ligands.

The synthesis and properties of 3 new ligand-bridged bimetallic complexes, 1(2+), 2(2+), and 3(2+), containing [RuCl([9]aneS(3))](+) metal centers are reported. Each complex was bridged by a different ditopic ligand. 1(2+) is bridged by 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (bptz), while 2(2+) and 3(2+) are bridged by 2,3-bis(2-pyridyl)pyrazine (dpp) and 2,2'-bipyrimidine (bpym), respectively. The Ru([II]) isovalent states of these complexes have been investigated using a variety of techniques. In the case of 3(2+), X-ray crystallography studies show preferential crystallization of an anti form with respect to coordinated chloride ligands (crystal data for [3][Cl(2)].4H(2)O: C(20)H(38)Cl(4)N(4)O(4)Ru(2)S(6), monoclinic, space group P2(1)/a, a = 10.929(14), b = 13.514(17), c = 11.299(16) A, beta = 90.52(1), V = 1669 A(3), Z = 2). UV/vis spectroscopy shows that spectra of these complexes are dominated by intraligand (pi-->pi) and metal-to-ligand Ru(d)-->L(pi) charge transfer transitions. Electrochemical studies reveal that metal-metal interactions are sufficiently intense to generate the Ru(III)/Ru(II) mixed valence [[RuCl([9]aneS(3))(2)](L-L)](3+) state, where L-L = individual bridging ligands. Although the 1(3+), 2(3+), and 3(3+) mixed valence states were EPR silent at room temperature and 77 K, isotropic solution spectra were observed for the electrochemically generated radical cations 1(+), 2(+), and 3(+), with 1(+) displaying well-resolved hyperfine coupling to bridging ligand nitrogens. Using UV/vis/NIR spectroelectrochemistry, we investigated optical properties of the mixed valence complexes. All three showed intervalence charge transfer (IVCT) bands that are much more intense than electrochemical data indicate. Indeed, a comparison of IVCT data for 1(3+) with an analogous structure containing [(NH3)(3)Ru](2+) metal centers shows that the IVCT in the new complex is an order of magnitude more intense. It is concluded that although the new complexes show relatively weak electrostatic interactions, they possess large resonance energies.