Racemic Ru Research Articles

RUNAT-BI: A Ruthenium(III) Complex as a Selective Anti-Tumor Drug Candidate against Highly Aggressive Cancer Cell Lines.

Ruthenium compounds have demonstrated promising activity in different cancer types, overcoming several limitations of platinum-based drugs, yet their global structure-activity is still under debate. We analyzed the activity of Runat-BI, a racemic Ru(III) compound, and of one of its isomers in eight tumor cell lines of breast, colon and gastric cancer as well as in a non-tumoral control. Runat-BI was prepared with 2,2'-biimidazole and dissolved in polyethylene glycol. We performed assays of time- and dose-dependent viability, migration, proliferation, and expression of pro- and antiapoptotic genes. Moreover, we studied the growth rate and cell doubling time to correlate it with the apoptotic effect of Runat-BI. As a racemic mixture, Runat-BI caused a significant reduction in the viability and migration of three cancer cell lines from colon, gastric and breast cancer, all of which displayed fast proliferation rates. This compound also demonstrated selectivity between tumor and non-tumor lines and increased proapoptotic gene expression. However, the isolated isomer did not show any effect. Racemic Runat-BI is a potential drug candidate for treatment of highly aggressive tumors. Further studies should be addressed at evaluating the role of the other isomer, for a more precise understanding of its antitumoral potential and mechanism of action.

Insight into achirality and chirality effects in interactions of an racemic ruthenium(II) polypyridyl complex and its Δ- and Λ-enantiomers with an RNA triplex

RNA triplexes have a variety of potential applications in molecular biology, diagnostics and therapeutics, while low stabilization of the third strand hinders their practical utilities under physiological conditions. In this regard, achieving the third-strand stabilization by binding small molecules is a promising strategy. Chirality is one of the basic properties of nature. To clarify achirality and chirality effects on the binding and stabilizing effects of RNA triplexes by small molecules, we report for the first time the RNA interactions of an racemic ruthenium(II) polypyridyl complex [Ru(bpy)2(11-CN-dppz)]2+ (rac-Ru1) and its two enantiomers Δ/Λ-[Ru(bpy)2(11-CN-dppz)]2+ (Δ/Λ-Ru1) with an RNA triplex poly(U-A*U) (where “-” represents Watson-Crick base pairing, and “*” denotes Hoogsteen base pairing, respectively) in this work. Research shows that although rac-Ru1 and its two enantiomers Δ/Λ-Ru1 bind to the RNA triplex through the same mode of intercalation, the binding affinity for enantiomer Δ-Ru1 is much higher than that for rac-Ru1 and enantiomer Λ-Ru1. However, compared to enantiomer Λ-Ru1, the binding affinity for rac-Ru1 does not show much of an advantage, which is slightly greater than that for the former. Thermal denaturation measurements reveal both rac-Ru1 and Δ-Ru1 to have a preference for stabilizing the third strand rather than the template duplex of the RNA triplex, while Λ-Ru1 stabilizes the RNA triplex without significant selectivity. Besides, the third-strand stabilizing effects by rac-Ru1 and Δ-Ru1 are not markedly different from each other, but more marked than that by Λ-Ru1. This work shows that the binding properties of the racemic Ru(II) polypyridyl complex with the RNA triplex are not simply an average of its two enantiomers, indicating potentially complicated binding events.

Luminescence of ruthenium(II) polypyridyls: evidence for intercalative binding to Z-DNA.

Photophysical studies have been undertaken to characterize the binding interactions of enantiomers of Ru(phen)3(2+), Ru(DIP)3(2+), and racemic Ru(bpy)2dppz2+ (where phen = 1,10-phenanthroline, DIP = 4,7-diphenylphenanthroline, and dppz = dipyridophenazine) with Z-form poly d(GC). Parallel enhancements in steady state luminescent intensity and a lengthening of luminescent lifetimes are seen for ruthenium enantiomers with Z-DNA as for B-DNA but with enantioselectivities reversed. Greater enhancements are seen for delta-isomers with the right-handed helix but for lambda-isomers with the left-handed helix. Ru(bpy)2dppz2+, an avid intercalator in B-DNA, displays no luminescence free in aqueous solution, but luminesces brightly bound to either B- or Z-poly d(GC). Stern-Volmer quenching studies also support the enantioselective preference in binding to B-DNA by delta-isomers and a reversal with binding to Z-DNA preferentially by the lambda-isomers. Steady state polarization studies indicate a rigid association of the complexes with both B- and Z-DNA on the time-scale of their emission and again with symmetrical enantioselectivities for the left and right-handed helices. Given the well characterized intercalative association of the complexes with B-DNA, the parallel results seen here with Z-DNA point strongly to a comparable intercalative association with the Z-form helix. That molecules may interact with Z-DNA through intercalation has not been demonstrated previously and now requires consideration in describing the range of interactions of small molecules and proteins with Z-DNA.

Enantioselective host–guest complexation of Ru(II) trisdiimine complexes using neutral and anionic derivatized cyclodextrins

Enantioselective host–guest complexation between five racemic Ru(II) trisdiimine complexes and eight derivatized cyclodextrins (CDs) has been examined by NMR techniques. The appearance of non-equivalent complexation-induced shifts of between the Δ and Λ-enantionomers of the Ru(II) trisdiimine complexes and derivatized CDs is readily observed by NMR. In particular, sulfobutyl ether-β-cyclodextrin sodium salt (SBE-β-CD), R-naphtylethyl carbamate β-cyclodextrin (RN-β-CD), and S-naphtylethyl carbamate β-cyclodextrin (SN-β-CD) showed good enantiodiscrimination for all five Ru complexes examined, which indicates that aromatic and anionic derivatizing groups are beneficial for chiral recognition. The complexation stoichiometry between SBE-β-CD and [Ru(phen) 3] 2+ was found to be 1:1 and binding constants reveal that Λ-[Ru(phen) 3] 2+ binds more strongly to SBE-β-CD than the Δ-enantiomer. Correlations between this NMR method and separative techniques based on CDs as chiral discriminating agents (i.e., selectors) are discussed in detail.

Inefficient Crystal Packing in Chiral [Ru(phen)3](PF6)2Enables Oxygen Molecule Quenching of the Solid-State MLCT Emission

The molecular oxygen quenching of the solid-state emission from pure crystals of Delta-Ru(phen)(3)(PF(6))(2), Lambda-Ru(phen)(3)(PF(6))(2), and racemic Ru(phen)(3)(PF(6))(2) (phen = 1,10-phenanthroline) was studied by emission spectroscopy. Crystals of the pure enantiomers exhibit significant and nearly identical emission-intensity quenching [0.36(2) and 0.33(2), respectively] in the presence of air [where the fraction quenched is (I(nitrogen) - I(air))/I(nitrogen)]; in comparison, the racemic compound shows a much lower value [0.05(2)]. The large difference in the quenching behavior is a result of major structural differences between the two chiral salts and the racemic salt. The chiral compounds crystallize in the space groups P4(1) and P4(3), respectively, with toluene and acetonitrile molecules in the lattice that can be partially removed to create void-space channels. These open channels allow the diffusion of oxygen molecules within the crystals and enable efficient emission quenching that is not possible in the closely packed racemic salt. Lifetime measurements, thermal gravimetric analysis, and single-crystal X-ray structure determinations support these conclusions.

Asymmetric Activation/Deactivation of Racemic Ru Catalysts for Highly Enantioselective Hydrogenation Irrespective of Ketonic Substrates: Molecular Design of Dimethylbinaphthylamine for Enantiomeric Catalysts Discrimination.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric Activation/Deactivation of Racemic Ru Catalysts for Highly Enantioselective Hydrogenation Irrespective of Ketonic Substrates: Molecular Design of Dimethylbinaphthylamine for Enantiomeric Catalysts Discrimination

AbstractAsymmetric activation and deactivation of racemic catalysts are two extremes in asymmetric catalysis. In a combination of these two protocols, higher enantioselectivity can be achieved by maximizing the difference in catalytic activity between the enantiomers of racemic catalysts through selective activation and deactivation of enantiomeric catalysts. 3,3′‐Dimethyl‐2,2′‐diamino‐1,1′‐binaphthyl (DM‐DABN) is thus designed as a chiral poison (deactivator) for complete enantiomer resolution of racemic BINAP‐Ru(II) catalysts. The catalyst system of DM‐DABN, 1,2‐diphenylethylenediamine (DPEN), and racemic BINAP‐Ru(II) led to great success in highly enantioselective hydrogenation irrespective of the ketonic substrates. The lower catalytic activity of the BINAP‐Ru(II)/DM‐DABN complex stems from the electron delocalization from the Ru center to the diamine moiety in contrast to the BINAP‐Ru(II)/DPEN complex where the highest electron densities are localized on the Ru‐N region. The present ‘asymmetric activation/deactivation protocol' can provide a guiding principle for the rational design of a molecule for enantiomeric discrimination between racemic catalysts.

ChemInform Abstract: Asymmetric Activation/Deactivation of Racemic Ru Catalysts for Highly Enantioselective Hydrogenation of Ketonic Substrates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Asymmetric Activation/Deactivation of Racemic Ru Catalysts for Highly Enantioselective Hydrogenation of Ketonic Substrates We are grateful to Drs. H. Kumobayashi and N. Sayo of the Takasago International Corp. for providing the BINAP ligands. We also thank Dr. Kenji Yoza of the Nippon Bruker Co. for X-ray analysis of the

Asymmetric Activation/Deactivation of Racemic Ru Catalysts for Highly Enantioselective Hydrogenation of Ketonic Substrates We are grateful to Drs. H. Kumobayashi and N. Sayo of the Takasago International Corp. for providing the BINAP ligands. We also thank Dr. Kenji Yoza of the Nippon Bruker Co. for X-ray analysis of the

Enantioselectivities in Electron-Transfer and Excited State Quenching Reactions of a Chiral Ruthenium Complex Possessing a Helical Structure

The outer-sphere electron-transfer reactions between diastereomers of Ru(menbpy)3•+ (menbpy = 4,4‘-di{(1R,2S,5R)-(−)-menthoxycarbonyl}-2,2‘-bipyridine) and enantiomers of Co(acac)3 and Co(edta)- have been studied by pulse radiolysis. Δ-Ru(menbpy)3•+ rapidly reduces Co(acac)3 in 85% EtOH/H2O (1 mM NaH2PO4) with second-order rate constants of (2.1 ± 0.1) × 107 and (7.8 ± 0.2) × 106 M-1 s-1 for the Δ- and Λ-Co(acac)3 enantiomers, respectively, and an enantioselectivity factor (ketΔ/ketΛ) of 2.7. Λ-Ru(menbpy)3•+ preferentially reduces Λ-Co(acac)3 with an enantioselectivity factor (ketΔ/ketΛ) of 0.8. Activation volume data (ΔV‡) suggest that the association between the Δ−Δ isomers in the encounter complex allows closer interaction of the metal centers than between the other isomer combinations. The value of ketΔ/ketΛ for the reaction of Δ- and Λ-Co(edta)- with Δ-Ru(menbpy)3•+ is 1.2. Electron-transfer reactions of seven racemic Ru(L)3•+ (L = substituted phenanthroline) complexes with Co(acac)3 were also studie...

Molecular Recognition of a Monoclonal Antibody (AC1106) Cross-Reactive for Derivatives of Ru(bpy)32+ and Ru(phen)32+

The characterization of a monoclonal antibody (AC1106) elicited via immunization with a Co(dmbpy)(bpy)23+−methyl viologen hapten (1) is described. AC1106 was found cross-reactive for a variety of luminescent ruthenium(II) metal complexes which served as useful probes to investigate the molecular recognition properties of this antibody. AC1106 was found to be specific for methylated derivatives of Ru(bpy)32+ and Ru(phen)32+ in the order of Ru(dmbpy)32+ > Ru(dmbpy)(bpy)22+ > Ru(dmphen)32+ > Ru(bpy)32+ ≫ Ru(phen)32+. The affinities of AC1106 for these metal complexes were found to range from ≥ 5 × 107 to ≤ 1 × 103 M-1. When bound (>98%) by AC1106, the luminescence decay traces for the racemic Ru(dmbpy)32+ and Ru(dmbpy)(bpy)22+ gave a satisfactory fit to a single-exponential decay process. Furthermore, D2O/H2O experiments with Ru(dmbpy)32+ indicate that AC1106 protects approximately 70% of the antibody-bound Ru(dmbpy)32+ from excited state deactivation by the solvent. Competition ELISA data indicate that both...

Effect of Negative Surface-Charge Densities of Smectite Clays on the Adsorption Isotherms of Racemic and Enantiomeric Tris(2,2′-Bipyridyl)Ruthenium(II) Chloride

AbstractThe level of adsorption of enantiomeric tris(2,2′-bipyridyl)ruthenium(II) (Ru(bpy)32+) by seven different smectite samples was found to be controlled by the total surface area of the clay. The level corresponded to one monolayer. The adsorption of the racemic mixture was lower for all samples, being limited to saturation of the clay's cation-exchange capacity. The addition of NaCl increased the adsorption of the racemic Ru(bpy)32+ to the same level as the enantiomers. The dependence on the clay's surface charge density, expected on the basis of the limited face-to-face aggregation model, was not found. The sharp decrease in adsorption of the enantiomers by low charge-density clays and the corresponding sharp increase in adsorption of the racemate by high charge density clays were not observed. These results do not necessarily invalidate the model. The range of negative charges examined may not have been wide enough. Also, charge distribution in smectite is generally not uniform.

Clay modified electrodes: Part 10. Studies of clay-adsorbed Ru(bpy) 2+3 enantiomers by UV-visible spectroscopy and cyclic voltammetry

The difference of a factor of 2 found in the values of c t the total concentration of adsorbed cation, between racemic Ru(bpy) 3Cl 2 and its enantiomers in clay modified electrodes, is attributed to differences in the effect of the adsorption of the cations on the degree of aggregation of the clays. UV-visible spectra indicate less aggregation of the clays upon addition of the enantiomers than the racemate, leaving more exposed surface for the adsorption of the ion pairs. This lower layering explains why the clays were found to adsorb twice their CEC (cation exchange capacity) for the enantiomers, but only their CEC for racemic Ru(bpy) 2+ 3, in contradiction to previous results with Ru(phen) 2+ 3, where it was the racemate that was reported to be adsorbed in excess of the CEC. Despite the differences in the values of c t, similar peak currents were found in the cyclic voltammograms of racemic Ru(bpy) 2+ 3 and its enantiomers in clay modified electrodes, since a smaller fraction of the adsorbed enantiomers were found to be electroactive. The decrease in currents due to this lower fraction more than makes up for their larger c t.