Exploration of the Pharmacophore for Cytoskeletal Targeting Ruthenium Polypyridyl Complexes.

Ruthenium(II) trisdiimine complexes of the formula, [Ru(dip) (L-L) ] , where n=0-3; dip=4,7-diphenyl-1,10-phenanthroline; L-L=2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen) were prepared and tested for cytotoxicity in two cell lines (H358, MCF7). Cellular uptake and subcellular localization were determined by harvesting treated cells and determining the ruthenium concentration in whole or fractionated cells (cytosolic, nuclear, mitochondrial/ ER/Golgi, and cytoskeletal proteins) by Ru ICP-MS. The logP values for the chloride salts of these complexes were measured and the data were analyzed to determine the role of lipophilicity versus structure in the various biological assays.

Metal-Catalyzed Hydride Transfer from Alcohols to Photoexcited Dipyridophenazine.

Dipyridophenazine (dppz) is known to react with alcohols upon photoexcitation into an n-π* transition at 378 nm to yield dihydrodipyridophenazine (dppzH ). This process occurs via H-atom abstraction from alcohols and subsequent disproportionation of the dppzH radical species, to the final product. This reaction shows a primary kinetic isotope effect (KIE = 4.

Roles of N-methyl-D-aspartate receptors and D-amino acids in cancer cell viability.

N-methyl-D-aspartate (NMDA) receptors, which are widely present in the central nervous system, have also been found to be up-regulated in a variety of cancer cells and tumors and they can play active roles in cancer cell growth regulation. NMDA receptor antagonists have been found to affect cancer cell viability and interfere with tumor growth. Moreover, cancer cells also have been shown to have elevated levels of some D-amino acids.

Disruption of microtubule function in cultured human cells by a cytotoxic ruthenium(ii) polypyridyl complex.

Treatment of malignant and non-malignant cultured human cell lines with a cytotoxic IC dose of ∼2 μM tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(ii) chloride () retards or arrests microtubule motion as tracked by visualizing fluorescently-tagged microtubule plus end-tracking proteins. Immunofluorescent microscopic images of the microtubules in fixed cells show substantial changes to cellular microtubule network and to overall cell morphology upon treatment with . Flow cytometry with MCF7 and H358 cells reveals only minor elevations of the number of cells in G/M phase, suggesting that the observed cytotoxicity is not tied to mitotic arrest.

Altered profiles and metabolism of l- and d-amino acids in cultured human breast cancer cells vs. non-tumorigenic human breast epithelial cells.

Herein we describe for the first time the endogenous levels of free l-and d-amino acids in cultured human breast cancer cells (MCF-7) and non-tumorigenic human breast epithelial cells (MCF-10A). d-Asp and d-Ser, which are co-agonists of the N-methyl-d-aspartate (NMDA) receptors, showed significantly elevated levels in MCF-7 cancer cells compared to MCF-10A cells. This may result from upregulated enzymatic racemases.

Synthesis, DNA Cleavage Activity, Cytotoxicity, Acetylcholinesterase Inhibition, and Acute Murine Toxicity of Redox-Active Ruthenium(II) Polypyridyl Complexes.

Four mononuclear [(L-L) Ru(tatpp)] and two dinuclear [(L-L) Ru(tatpp)Ru(L-L) ] ruthenium(II) polypyridyl complexes (RPCs) containing the 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (tatpp) ligand were synthesized, in which L-L is a chelating diamine ligand such as 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me phen) or 4,7-diphenyl-1,10-phenanthroline (Ph phen). These Ru-tatpp analogues all undergo reduction reactions with modest reducing agents, such as glutathione (GSH), at pH 7. These, plus several structurally related but non-redox-active RPCs, were screened for DNA cleavage activity, cytotoxicity, acetylcholinesterase (AChE) inhibition, and acute mouse toxicity, and their activities were examined with respect to redox activity and lipophilicity.

Cellular and cell-free studies of catalytic DNA cleavage by ruthenium polypyridyl complexes containing redox-active intercalating ligands.

The ruthenium(ii) polypyridyl complexes (RPCs), [(phen)Ru(tatpp)] ( ) and [(phen)Ru(tatpp)Ru(phen)] ( ) are shown to cleave DNA in cell-free studies in the presence of a mild reducing agent, glutathione (GSH), in a manner that is enhanced upon lowering the [O]. Reactive oxygen species (ROS) are involved in the cleavage process as hydroxy radical scavengers attenuate the cleavage activity. Cleavage experiments in the presence of superoxide dismutase (SOD) and catalase reveal a central role for HO as the immediate precursor for hydroxy radicals.

Solar photothermochemical alkane reverse combustion.

A one-step, gas-phase photothermocatalytic process for the synthesis of hydrocarbons, including liquid alkanes, aromatics, and oxygenates, with carbon numbers (Cn) up to C13, from CO2 and water is demonstrated in a flow photoreactor operating at elevated temperatures (180-200 °C) and pressures (1-6 bar) using a 5% cobalt on TiO2 catalyst and under UV irradiation. A parametric study of temperature, pressure, and partial pressure ratio revealed that temperatures in excess of 160 °C are needed to obtain the higher Cn products in quantity and that the product distribution shifts toward higher Cn products with increasing pressure. In the best run so far, over 13% by mass of the products were C5+ hydrocarbons and some of these, i.

Photodriven Multi-electron Storage in Disubstituted Ru(II) Dppz Analogues.

Four derivatives of the laminate acceptor ligand dipyrido-[3,2-a:2',3'-c]phenazine (dppz) and their corresponding ruthenium complexes, [Ru(phen)2 (dppzX2 )](2+) , were prepared and characterized by NMR spectroscopy, ESI-MS, and elemental analysis. The new ligands, generically denoted dppzX2 , were symmetrically disubstituted on the distal benzene ring to give 10,13-dibromodppz (dppz-p-Br), 11,12-dibromodppz (dppz-o-Br), 10,13-dicyanodppz (dppz-p-CN), 11,12-dicyanodppz (dppz-o-CN). Solvated ground state MO calculations of the ruthenium complexes reveal that these electron-withdrawing substituents not only lower the LUMO of the dppz ligand (dppz(CN)2 View Article and Find Full Text PDF

Thermodynamic investigations of [(phen)2Ru(tatpp)Ru(phen)2](4+) interactions with B-DNA.

While the antitumor activity of P(4+) is relatively well understood, the binding mechanism and thermodynamics for formation of (P(4+)·DNA) complexes remain in question. The thermodynamic parameters (Ka, ΔG, ΔH, and -TΔS) for formation of DNA complexes of the ruthenium dimer, [(phen)2Ru(tatpp)Ru(phen)2](4+) (abbreviated as P(4+)), where phen is 1,10-phenanthroline and tatpp is 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3″,2″-1:2‴,3‴-n]-pentacene, were determined using isothermal titration calorimetry. Calorimetric and spectroscopic titration experiments were performed in which P(4+) was added to three duplex DNAs of different lengths.

Enantiomeric separations of ruthenium (II) polypyridyl complexes using HPLC with cyclofructan chiral stationary phases.

The enantiomeric separation of 21 ruthenium (II) polypyridyl complexes was achieved with a novel class of cyclofructan-based chiral stationary phases (CSPs) in the polar organic mode. Aromatic derivatives on the chiral selectors proved to be essential for enantioselectivity. The R-napthylethyl carbamate functionalized cyclofructan 6 (LARIHC CF6-RN) column proved to be the most effective overall, while the dimethylphenyl carbamate cyclofructan 7 (LARIHC CF7-DMP) showed complementary selectivity.

Photochemical reduction of carbon dioxide to methanol and formate in a homogeneous system with pyridinium catalysts.

Photochemical catalytic CO2 reduction to formate and methanol has been demonstrated in an aqueous homogeneous system at pH 5.0 comprising ruthenium(II) trisphenanthroline as the chromophore, pyridine as the CO2 reduction catalyst, KCl, and ascorbic acid as a sacrificial reductant, using visible light irradiation at 470 ± 20 nm. Isotopic labeling with (13)CO2 yields the six-electron-reduced product (13)CH3OH.

Water detection by "turn on" fluorescence of the quinone-containing complexes [Ru(phen)2(1,10-phenanthroline-5,6-dione)2+] and [Ru(phenanthroline-5,6-dione)3]2+.

Addition of water to the quinone functions in [Ru(phen)2(pdn)](2+) (1) and [Ru(pdn)3](2+) (2) (where phen = 1,10-phenanthroline and pdn = 1,10-phenanthroline-5,6-dione) turns on fluorescence at 605 nm, as formation of the geminal diol eliminates the predominant quinone-based non-radiative decay pathway and gives rise to a long-lived (3)MLCT state similar in nature to that seen in [Ru(phen)3](2+). Using NMR, the equilibrium constant for the hydration reaction of 1 in acetonitrile was determined to be 0.0253.

Long-lived, directional photoinduced charge separation in RuII complexes bearing laminate polypyridyl ligands.

RuII complexes incorporating both amide-linked bithiophene donor ancillary ligands and laminate acceptor ligands; dipyrido[3,2-a:2',3'-c]phenazine (dppz), tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine (tpphz), and 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3''']-pentacene (tatpp) exhibit long-lived charge separated (CS) states, which have been analyzed using time-resolved transient absorption (TA), fluorescence, and electronic absorption spectroscopy in addition to ground state electrochemical and spectroelectrochemical measurements. These complexes possess two electronically relevant ³MLCT states related to electron occupation of MOs localized predominantly on the proximal "bpy-like" portion and central (or distal) "phenazine-like" portion of the acceptor ligand as well as energetically similar ³LC and ³ILCT states. The unusually long excited state lifetimes (τ up to 7 μs) observed in these complexes reflect an equilibration of the ³MLCTprox or ³MLCTdist states with additional triplet states, including a ³LC state and a ³ILCT state that formally localizes a hole on the bithiophene moiety and an electron on the laminate acceptor ligand.

Regression of lung cancer by hypoxia-sensitizing ruthenium polypyridyl complexes.

The ruthenium (II) polypyridyl complexes (RPC), Δ-[(phen)2Ru(tatpp)]Cl2 (Δ-[3]Cl2) and ΔΔ-[(phen)2Ru(tatpp)Ru(phen)2]Cl4 (ΔΔ-[4]Cl4, are a new generation of metal-based antitumor agents. These RPCs bind DNA via intercalation of the tatpp ligand, which itself is redox-active and is easily reduced at biologically relevant potentials. We have previously shown that RPC 4(4+) cleaves DNA when reduced by glutathione to a radical species and that this DNA cleavage is potentiated under hypoxic conditions in vitro.

Cleavage of DNA by proton-coupled electron transfer to a photoexcited, hydrated Ru(II) 1,10-phenanthroline-5,6-dione complex.

Visible light irradiation of a ruthenium(II) quinone-containing complex, [(phen)(2)Ru(phendione)](2+) (1(2+)), where phendione = 1,10-phenanthroline-5,6-dione, leads to DNA cleavage in an oxygen independent manner. A combination of NMR analyses, transient absorption spectroscopy, and fluorescence measurements in water and acetonitrile reveal that complex 1(2+) must be hydrated at the quinone functionality, giving [(phen)(2)Ru(phenH(2)O)](2+) (1H(2)O(2+), where phenH(2)O = 1,10-phenanthroline-6-one-5-diol), in order to access a long-lived (3)MLCT(hydrate) state (τ ∼ 360 ns in H(2)O) which is responsible for DNA cleavage. In effect, hydration at one of the carbonyl functions effectively eliminates the low-energy (3)MLCT(SQ) state (Ru(III) phen-semiquinone radical anion) as the predominant nonradiative decay pathway.

Air impacts from three alternatives for producing JP-8 jet fuel.

Unlabelled: To increase U.S. petroleum energy independence, the University of Texas at Arlington (UT Arlington) has developed a direct coal liquefaction process which uses a hydrogenated solvent and a proprietary catalyst to convert lignite coal to crude oil.

Analysis and comparison of inertinite-derived adsorbent with conventional adsorbents.

Unlabelled: To increase U.S. petroleum energy-independence, the University of Texas at Arlington (UT Arlington) has developed a coal liquefaction process that uses a hydrogenated solvent and a proprietary catalyst to convert lignite coal to crude oil.

Ligand-triplet-fueled long-lived charge separation in ruthenium(II) complexes with bithienyl-functionalized ligands.

Ruthenium(II) polypyridyl complexes with pendant bithienyl ligands exhibiting unusually long-lived (τ ~ 3-7 μs) charge-separated excited states and a large amount of stored energy (ΔG° ~ 2.0 eV) are reported. A long-lived ligand-localized triplet acts as an energy reservoir to fuel population of an interligand charge-transfer state via an intermediate metal-to-ligand charge-transfer state in these complexes.

Photochemical two-electron reduction of a dinuclear ruthenium complex containing a bent tetraazatetrapyridopentacene bridging ligand: pushing up the LUMO for storing more energy.

The synthesis and characterization of a ditopic bridging ligand, 9,12,21,22-tetraazatetrapyrido[3,2-a:2',3'-c:3″2″-m:2''',3'''-o]pentaphene (tatppα) and its dinuclear ruthenium complex, [(phen)(2)Ru(tatppα)Ru(phen)(2)][PF(6)](4) (1(4+)), are described. The tatppα ligand is structurally very similar to 9,10,20,33-tetraazatetrapyrido[3,2-a:2',3'-c:3″,2″-l:2''',3'''-n]pentacene (tatppβ), except that, instead of a linear tetraazapentacene backbone, tatppα has an ortho (or α) substitution pattern about the central benzene ring, leading to a 120° bend. Complex 1(4+) shows tatppα-based reductions at -0.

Photoinduced ligand transformations in a ruthenium complex of dimethoxytetrapyridotetraazapentacene.

The dinuclear ruthenium(II) complex [(phen)(2)Ru(tatpOMe)Ru(phen)(2)](4+) (2(4+); phen is 1,10-phenanthroline and tatpOMe is 10,21-dimethoxy-9,10,20,33-tetraazatetrapyrido[3,2-a:2'3'-c:3'',2''-l:2''',3'''-n]pentacene) has been synthesized and characterized by (1)H NMR, ESI mass spectroscopy and elemental analysis. Loss of methoxy group from bridging ligand of complex 2(4+) due to irradiation is observed by (1)H NMR and photochemistry. The interrelated electronic properties UV-Vis, electrochemistry, photochemistry and molecular orbital calculation are analyzed and discussed on the bridging ligand of the complex 2(4+).

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.

Study of a new chiral selector: Sodium arsenyl-(l)-(+) tartrate for capillary electrophoresis.

Sodium arsenyl-(l)-(+) tartrate (Na(2)[As(2)(+)-tart(2)].3H(2)O) was examined and evaluated as a chiral selector using capillary electrophoresis. This chiral selector showed enantioselective associations with many cationic analytes, including primary, secondary, and tertiary amines.