Hydrogen storage and delivery: immobilization of a highly active homogeneous catalyst for the decomposition of formic acid to hydrogen and carbon dioxide

The homogeneous catalytic system, based on water-soluble ruthenium(II)-TPPTS catalyst (TPPTS=meta-trisulfonated triphenylphosphine), selectively decomposes HCOOH into H2 and CO2 in aqueous solution. Although this reaction results in only two gas products, heterogeneous catalysts could be advantageous for recycling, especially for dilute formic acid solutions, or for mobile, portable applications. Several approaches have been used to immobilize/solidify the homogeneous ruthenium-TPPTS catalyst based on ion exchange, coordination and physical absorption. The activity of the various heterogeneous catalysts for the decomposition of formic acid has been determined. These heterogenized catalysts offer the advantage of easy catalyst separation/recycling in dilute formic acid, or for mobile, portable application

Potential of cycloaddition reactions to generate cytotoxic metal drugs in vitro

Severe general toxicity issues blight many chemotherapeutics utilized in the treatment of cancers, resulting in the need for more selective drugs able to exert their biological activity at only the required location(s). Toward this aim, we report the development of an organometallic ruthenium compound, functionalized through a η6-bound arene ligand with a bicyclononyne derivative, able to participate in strain-promoted cycloaddition reactions with tetrazines. We show that combination of the ruthenium compound with a ditetrazine in biological media results in the in situ formation of a dinuclear molecule that is more cytotoxic toward cancer cells than the starting mononuclear ruthenium compound and tetrazine components. Such an approach may be extended to in vivo applications to construct a cytotoxic metallodrug at a tumor site, providing a novel approach toward the turn-on cytotoxicity of metallodrugs in the treatment of cancer

Conformational control of anticancer activity: the application of arene-linked dinuclear ruthenium(II) organometallics

Dinuclear metal complexes have emerged as a promising class of biologically active compounds which possess unique anticancer activity. Here, we describe a novel series of arene-linked dinuclear organometallic Ru(II) complexes, where the relative conformation of the ruthenium centres is controlled by the stereochemical configuration of 1,2-diphenylethylenediamine linker moieties, as confirmed by X-ray crystallography. The reactivity and cytotoxicity of these compounds is compared to flexible dinuclear and mononuclear analogues, demonstrating in all cases the complexes can undergo aquation, coordinate to typical biological donor ligands and importantly, in the case of dinuclear analogues, crosslink oligonucleotide and peptide sequences. Differences in the conformation of the isomeric dinuclear compounds lead to significantly different levels of cytotoxicity against A2780, A2780cisR and HEK-293 cell lines; isomers with a closed conformation are significantly more cytotoxic than isomers with a more open conformation and they are also significantly less susceptible to acquired resistance mechanisms operating in the A2780cisR cell line. These rigid dinuclear compounds possess markedly increased cytotoxicity relative to the non-cytotoxic mononuclear analogues that does not appear to be related to differences in complex lipophilicity or cellular uptake, which, in general, remain similar in magnitude across the series. Thus, the molecular conformation of such dinuclear species may be crucial in determining the nature of the adducts formed on coordination to biological targets in a cellular environment, and opens up a novel route toward the development of more active metal-based anticancer agents

Metabolization of [Ru(η6-C6H5CF3)(pta)Cl2]: a cytotoxic RAPTA-type complex with a strongly electron withdrawing arene ligand

The anticancer ruthenium-arene compound [Ru(η6-C6H5CF3)(pta)Cl2] (where pta is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane), termed RAPTA-CF3, with the electron-withdrawing α,α,α-trifluorotoluene ligand, is one of the most cytotoxic RAPTA compounds known. To rationalize the high observed cytotoxicity, the hydrolysis of RAPTA-CF3 in water and brine (100mM sodium chloride) and its reactions with the protein ubiquitin and a double-stranded oligonucleotide (5′-GTATTGGCACGTA-3′) were studied using NMR spectroscopy, high-resolution Fourier transform ion cyclotron resonance mass spectrometry, and gel electrophoresis. The aquation of the ruthenium-chlorido complex was accompanied by a loss of the arene ligand, independent of the chloride concentration, which is a special property of the compound not observed for other ruthenium-arene complexes with relatively stable ruthenium-arene bonds. Accordingly, the mass spectra of the biomolecule reaction mixtures contained mostly [Ru(pta)]-biomolecule adducts, whereas [Ru(pta)(arene)] adducts typical of other RAPTA compounds were not observed in the protein or DNA binding studies. Gel electrophoresis experiments revealed a significant degree of decomposition of the oligonucleotide, which was more pronounced in the case of RAPTA-CF3 compared with RAPTA-C. Consequently, facile arene loss appears to be responsible for the increased cytotoxicity of RAPTA-CF3. Graphical abstract: RAPTA-CF3 is a fast-acting cytotoxic compound that degrades DNA and has a mode of action fundamentally different from that of other ruthenium(II)-arene compound

Ruthenium versus platinum: interactions of anticancer metallodrugs with duplex oligonucleotides characterised by electrospray ionisation mass spectrometry

The binding of the ruthenium-based anticancer drug candidates KP1019, NAMI-A and RAPTA-T towards different double-stranded oligonucleotides was probed by electrospray ionisation mass spectrometry and compared with that of the widely used platinum-based chemotherapeutics cisplatin, carboplatin and oxaliplatin. It was found that the extent of adduct formation decreased in the following order: cisplatin>oxaliplatin>NAMI-A>RAPTA-T>carboplatin>KP1019. In addition to the characterisation of the adducts formed with the DNA models, the binding sites of the metallodrugs on the oligonucleotides were elucidated employing top-down tandem mass spectrometry and were found to be similar for all the metallodrugs studied, irrespective of the sequence of the oligonucleotide. A strong preference for guanine residues was establishe

Exploring the individualized experiences of participants in a responsibility-based youth development program

Youth development programs are built upon the assumption that individual participants have a unique set of strengths, needs, and developmental opportunities. The same is true of the Teaching Personal and Social Responsibility (TPSR) model. Although TPSR calls for individualized curricula and differentiated instruction, these topics have not been sufficiently examined in the literature. The current study provides case studies of four purposefully selected African American adolescent males and their experience in a community-based TPSR program. Findings are used to evaluate the program in terms of providing meaningful experiences to individual participants and illuminating the importance of considering individual differences among participants even when they have many characteristics in common. Implications for teaching and research are discussed.Los programas de desarrollo juvenil se basan en la suposición de que los individuos que participan tienen un conjunto de puntos fuertes, necesidades y oportunidades de desarrollo. Esto es aplicable también al modelo de Enseñanza de la Responsabilidad Personal y Social (TPSR). Aunque el TPSR los participantes requiere una individualización del curriculum y una instrucción diferenciada, dichos asuntos no han sido suficientemente estudiados. El presente escrito proporciona los estudios de caso de cuatro varones adolescentes afro-americanos, intencionalmente seleccionados, y su experiencia en un programa comunitario de TPSR. Los resultados se utilizan para evaluar si el programa proporciona experiencias significativas a los jóvenes y para destacar la importancia de considerar las diferencias individuales de los partcipantes, incluso cuando tienen muchas características en común. Se abordan también sus implicaciones para la enseñanza y la investigación

Enhancement of Cytotoxicity by Combining Pyrenyl-Dendrimers and Arene Ruthenium Metallacages

Three generations of pyrenyl bis-MPA dendrimers with two different end-groups, acetonide (pyrGn) or alcohol (pyrGn-OH) (n = 1–3), were synthesized, and the pyrenyl group of the dendritic molecules was encapsulated in the arene ruthenium metallacages, [Ru6(p-cymene) 6 (OO∩OO)3(tpt)2]6+ (OO∩OO = 5,8-dioxydo- 1,4-naphtaquinonato (donq) [1]6+ and 6,11-dioxydo-5,12- naphtacenedionato (dotq) [2]6+; tpt =2,4,6-tri(pyridin-4-yl)-1,3,5-triazine). The host–guest properties of [guestC1]6+ and [guestC2]6+ were studied in solution by NMR and UV–vis spectroscopic methods, thus allowing the determination of the affinity constants. Moreover, the cytotoxicity of these water- soluble host–guest systems and the pyrenyl-dendrimers was evaluated on human ovarian cancer cells

Long-Lived Venus Lander Conceptual Design: How To Keep It Cool

Surprisingly little is known about Venus, our neighboring sister planet in the solar system, due to the challenges of operating in its extremely hot, corrosive, and dense environment. For example, after over two dozen missions to the planet, the longest-lived lander was the Soviet Venera 13, and it only survived two hours on the surface. Several conceptual Venus mission studies have been formulated in the past two decades proposing lander architectures that potentially extend lander lifetime. Most recently, the Venus Science and Technology Definition Team (STDT) was commissioned by NASA to study a Venus Flagship Mission potentially launching in the 2020- 2025 time-frame; the reference lander of this study is designed to survive for only a few hours more than Venera 13 launched back in 1981! Since Cytherean mission planners lack a viable approach to a long-lived surface architecture, specific scientific objectives outlined in the National Science Foundation Decadal Survey and Venus Exploration Advisory Group final report cannot be completed. These include: mapping the mineralogy and composition of the surface on a planetary scale determining the age of various rock samples on Venus, searching for evidence of changes in interior dynamics (seismometry) and its impact on climate and many other key observations that benefit with time scales of at least a full Venus day (Le. daylight/night cycle). This report reviews those studies and recommends a hybrid lander architecture that can survive for at least one Venus day (243 Earth days) by incorporating selective Stirling multi-stage active cooling and hybrid thermoacoustic power