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The synthesis of a new RuII complex, in which the metal is coordinated by two 1,10-phenanthroline ligands and a 2,2&prime, bipyridyl unit linked, via methylene bridges in its 4 and 4&prime, positions, to two 1,4,7,10-tetraazacyclododecane (cyclen) macrocycles ([Ru(phen)2L]2+) is reported. Protonation and ZnII binding by [Ru(phen)2L]2+ have been analyzed by potentiometric titration, evidencing the formation of mixed hetero-binuclear and hetero-trinuclear ZnII/RuII complexes. These complexes were tested as bis-phenol A (BPA) binders. Only the dizinc complex with [Ru(phen)2L]2+ is able to bind BPA in aqueous solution, affording a remarkably stable {Zn2[Ru(phen)2L]BPA(H&minus, 2)}4+ adduct at neutral pH, in which BPA is bound in its doubly deprotonated form to the two ZnII ions. BPA binding was found to quench the luminescence emission of the RuII(phen)2bipy core. Although the quenching effect is modest, this study demonstrates that appropriately designed dizinc complexes can be used for binding and optical sensing of BPA in water.

Two cationic ruthenium(II) 1,4,7-trithiacyclononane ([9]aneS3) complexes of curcumin (curcH) and bisdemethoxycurcumin (bdcurcH), namely [Ru(curc)(dmso-S)([9]aneS3)]Cl (1) and [Ru(bdcurc)(dmso-S)([9]aneS3)]Cl (2) were prepared from the [RuCl2(dmso-S)([9]-aneS3)] precursor and structurally characterized, both in solution and in the solid state by X-ray crystallography. The corresponding PTA complexes [Ru(curc)(PTA)([9]aneS3)]Cl (3) and [Ru(bdcurc)(PTA)([9]aneS3)]Cl (4) have been also synthesized and characterized (PTA = 1,3,5-triaza-7-phosphaadamantane). Bioinorganic studies relying on mass spectrometry were performed on complexes 1–4 to assess their interactions with the model protein lysozyme. Overall, a rather limited reactivity with lysozyme was highlighted accompanied by a modest cytotoxic potency against three representative cancer cell lines. The moderate pharmacological activity is likely connected to the relatively high stability of these complexes.

In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium-based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple-negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced next-generation metallotherapeutics, with NAMI-A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex—named AziRu—incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well-known NAMI-A complex, information on non-nanostructured Ru-based anticancer agents have been included in a precise manner.

The success of platinum complexes as chemiotherapeutic drugs pushed the scientific community to design new transition metal based complexes. to fight cancer and overcome the severe side effects and the insurgence of platinum resistance [1]..Among these compound ruthenium (III) complexes have been demonstrated very powerful against metastatic tumour but very poor is their action as cytotoxic agent.[2] The first aim of the present study was the development of a new ruthenium(III) complex, belonging to NAMI-A class, bearing to pyridine ligand a fully protected sugar moiety (RuPyTri). The presence of carbohydrate in coordination sphere should increase the complex ability to cross cellular membranes and sets this molecule in the area of biocompatible agents as tumour drug. The stability of the complex was studied and compared to RuPy complex in solution at different pH following UV-VIS spectra. The second, more relevant, purpose was to verify the ruthenium complexes activity after loading into liposomes. Liposomes can induce different mechanisms of delivery, increase the ability to cross cell membrane and stabilize the complexes reducing the water exchange. The lipid composition Egg L-α-phosphatidylcholine cholesterol / DSPE-PEG liposomes was selected to reproduce analog supramolecular aggregates in clinical use to vehicle doxorubicin (Doxil). Ruthenium complexes were loaded into liposomes using the passive equilibration loading method estimating the entrapped metal amount by ICP-MS. Full drug containing liposomes were structurally characterized by dynamic light scattering (DLS). Measurements confirm that sizes of all liposomes are in the 100 nm range, suitable for in vivo use. Loading ability and release kinetic allowed to select the best ratio between the lipid fraction and the metal to be tested in cellular experiments. Stability and drug release properties of ruthenium containing liposomes were confirmed in buffer. The growth inhibitory effects of both liposomal and free complex in PC3 prostate cancer cell lines validate a high cytotoxic ability of the liposome entrapped ruthenium (III) complexes.

A simple and expeditious microwave-assisted procedure for the synthesis of a variety of Shvo-type ruthenium complexes has been developed by reacting Ru3(CO)12 with variously functionalized tetraarylcyclopentadienones under microwave irradiation in MeOH. Ligand precursors have also been prepared under microwave heating by a bis-aldol condensation of 1,3-diphenylacetone with variously functionalized aromatic diketones. All the reactions were very fast and clean, leading to good yields and purities.

A straightforward and efficient synthetic route to novel Ru N-heterocyclic carbene (NHC) complexes by transmetallation of non-bulky silver NHC to ruthenium dicarbonyl tetraarylcyclopentadienone is described. The same procedure with sterically demanding NHC leads to unprecedented heterobimetallic Ru–Ag(NHC) complexes.

Four structurally related Ru(II)-halide-PTA complexes, of general formula trans- or cis-[Ru(PTA)4X2] (PTA = 1,3,5-triaza-7-phosphaadamantane, X = Cl (1, 2), Br (3, 4), were prepared and characterized. Whereas compounds 1 and 2 are known, the corresponding bromo derivatives 3 and 4 are new. The Ru(III)-PTA compound trans-[RuCl4(PTAH)2]Cl (5, PTAH = PTA protonated at one N atom), structurally similar to the well-known Ru(III) anticancer drug candidates (Na)trans-[RuCl4(ind)2] (NKP-1339, ind = indazole) and (Him)trans-[RuCl4(dmso-S)(im)] (NAMI-A, im = imidazole), was also prepared and similarly investigated. Notably, the presence of PTA confers to all complexes an appreciable solubility in aqueous solutions at physiological pH. The chemical behavior of compounds 1–5 in water and in physiological buffer, their interactions with two model proteins – cytochrome c and ribonuclease A – as well as with a single strand oligonucleotide (5′-CGCGCG-3′), and their in vitro cytotoxicity against a human colon cancer cell line (HCT-116) and a myeloid leukemia (FLG 29.1) were investigated. Upon dissolution in the buffer, sequential halide replacement by water molecules was observed for complexes 1–4, with relatively slow kinetics, whereas the Ru(III) complex 5 is more inert. All tested compounds manifested moderate antiproliferative properties, the cis compounds 2 and 4 being slightly more active than the trans ones (1 and 3). Mass spectrometry experiments evidenced that all complexes exhibit a far higher reactivity towards the reference oligonucleotide than towards model proteins. The chemical and biological profiles of compounds 1–5 are compared to those of established ruthenium drug candidates in clinical development.

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Currently there are about 35.6 million people diagnosed with Alzheimer's disease (AD) in the world, and it is expected that this number will double by 2050. Causes of Alzheimer's disease are not yet known, but their symptoms are characterized the decline of cognitive function result of overactivity of the enzyme acetylcholinesterase (AChE); and accumulation of β-amyloid peptide (β-A) in the brain of patients. Therefore it is important to the development of drugs that act on the two problems of AD; cognitive decline (inhibition of AChE activity) and the identification of fibrillar aggregates of β-A (creation of new probes). For this purpose have been prepared and tested a series of luminescent complex; cis-[Ru(phen)2(4- ImAC)]PF6, cis-[Ru(phen)2(4-ImAAc)]PF6, cis-[Ru(phen)2(2-Apy)](PF6)2, where phen = 1,10-phenanthroline, ImAA = 4-imidazole acetic acid, ImAC = 4-imidazole carboxylic acid and Apy = 2-aminopyridine. The ruthenium complexes were synthesized, where its structural elucidation and purity were checked by NMR H1 spectroscopy and by microanalysis. The compounds are soluble in aqueous solutions and exhibit an intense and broad absorption and emission in the visible region. The complexes have relatively long life with 1 the order of 100 ns. The complexes showed moderate inhibition against the enzyme AChE, with an IC50 of about 10-20 μmol.L-1. From the images from confocal microscopy was possible to make the location of the complex inside the cells by luminescent emission, where the imidazole compounds were located specifically in the cytoplasmic portion of the cell, unlike the complex with aminopyridine, which was distributed homogeneously throughout cellular portion. It was possible to identify the formation of fibers from measurements of emission of the luminescent complex, since these complexes have intensity of luminescence variable with different types of Aβ aggregation. The fibrils were also confirmed by fluorescence microscopy emission lifetime. From the results of the complexes exhibit high pharmacological potential to the treatment of AD since they can be used in diagnosis (identification of the fibrils) and in the treatment of AD (AChE inhibition). Atualmente existem cerca de 35,6 milhões de pessoas diagnósticadas com a doença de Alzheimer (DA) no mundo, e espera-se que este número duplique até 2050. As causas da doença de Alzheimer, ainda não são conhecidas, mas seus sintomas são caracterizados pelo declínio da função cognitiva resultado da superatividade da enzima acetilcolinesterase (AChE); e à acumulação do peptídeo β-amilóide (β-A) no cérebro dos doentes. Diante disso é importante o desenvolvimento de fármacos que atuem nos dois problemas da DA; tanto no declínio cognitivo (inibição da atividade da AChE) e na identificação dos agregados fibrilares de β-A (criação de novas sondas). Para esta finalidade foram preparados e ensaiados uma série de complexos luminescentes cis-[Ru(phen)2(4-ImAC)]PF6, cis- [Ru(phen)2(4-ImAAc)]PF6, cis-[Ru(phen)2(2-Apy)](PF6)2, onde phen=1,10- fenantrolina, ImAA= 4-imidazol ácido acético, ImAC= 4-imidazol ácido carboxílico e Apy= 2-aminopiridina. Os complexos de rutênio foram sintetizados, onde sua elucidação estrutural e grau de pureza foram verificados por espectroscopia de RMN de H1 e por análise elementar. Os compostos são solúveis em solução aquosa e exibem uma intensa e larga absorção e emissão na região do visível. Os complexos apresentaram tempo de vida relativamente longo, onde o 1 encontrado foi da ordem de 100 ns. Os complexos exibiram inibição moderada frente à enzima AChE, com um IC50 da ordem de 10-20 μmol.L-1. A partir da imagens de microscopia confocal foi possível fazer a localização dos complexos no interior celular, através da emissão luminescente, onde os compostos imidazólicos se localizaram especificadamente na porção citoplasmática das células, e o complexo com aminopiridina, se distribuiu de forma homogênea em toda a porção celular. Foi possível acompanhar a formação das fibras a partir das medidas de emissão dos complexos, uma vez que os compostos apresentam intensidade de luminescência variável aos diferentes tipos de agregação do β-A. As fibrilas também foram confirmadas por microscopia fluorescente de tempo de vida de emissão. A partir dos resultados os complexos exibem grande potencial farmacológico frente ao tratamento da DA, uma vez que podem ser utilizados tanto no diagnóstico (identificação das fibrilas) e no tratamento da DA (inibição da AChE).

Some pentamethylcyclopentadienyl ruthenium(II) diphosphine chloride complexes have been prepared by ligand exchange starting with the parent triphenylphosphine derivatives and their reactivities compared with those of the corresponding cyclopentadienyl compounds. The pentamethyl ligand causes a greater extent of asymmetric induction when the (R)-prophos and (R)-phenphos ligands are used as well as a higher lability of the stereochemistry at the stereogenic ruthenium centre. A shift of about 200 mV in the oxidation potential is caused by the substitution at the penta-hapto ligand. The order of basicity of the diphosphine ligands was also evaluated and was found to be consistent with previous determinations. The crystal structure of(eta(5)-C5Me5)Ru {(S,S)-chiraphos}Cl shows a coordination around the ruthenium atom similar to that found for the (eta(5)-C5H5)Ru{(S,S) -chiraphos}Cl complex. (C) 1998 Elsevier Science S.A. All rights reserved.

Not available, Parce qu'ils offrent de nombreux avantages par rapport aux méthodes classiques de mesure, les capteurs chimiques optiques, ou optodes, connaissent un large succès depuis une quinzaine d'années. De nombreux analytes peuvent être dosés par ces méthodes. Comme il prend part à beaucoup de phénomènes chimiques et biochimiques, l'oxygène est l'un des plus souvent cité. La mesure est fondée sur l'inhibition, par l'oxygène, de la fluorescence d'un indicateur. La connaissance de l'intensité ou plutôt de la durée de vie de fluorescence permet de déterminer la concentration en oxygène autour de l'indicateur placé à l'extrémité d'une ou plusieurs fibres optiques. Nous nous sommes intéressés à l'application de cette nouvelle voie de mesure au milieu marin. Après avoir mis au point et caractérisé un dispositif de mesure de durée de vie de fluorescence, deux composés fluorescents ont été étudiés: le pyrène et le tris(1,10-phénantroline)ruthenium(ii) chloride hydrate. La calibration en fonction de l'oxygène a été effectuée et pour le second composé, qui s'est révélé plus performant, les influences de la température, de la salinité et de la pression hydrostatique ont été étudiées

Not available, Parce qu'ils offrent de nombreux avantages par rapport aux méthodes classiques de mesure, les capteurs chimiques optiques, ou optodes, connaissent un large succès depuis une quinzaine d'années. De nombreux analytes peuvent être dosés par ces méthodes. Comme il prend part à beaucoup de phénomènes chimiques et biochimiques, l'oxygène est l'un des plus souvent cité. La mesure est fondée sur l'inhibition, par l'oxygène, de la fluorescence d'un indicateur. La connaissance de l'intensité ou plutôt de la durée de vie de fluorescence permet de déterminer la concentration en oxygène autour de l'indicateur placé à l'extrémité d'une ou plusieurs fibres optiques. Nous nous sommes intéressés à l'application de cette nouvelle voie de mesure au milieu marin. Après avoir mis au point et caractérisé un dispositif de mesure de durée de vie de fluorescence, deux composés fluorescents ont été étudiés: le pyrène et le tris(1,10-phénantroline)ruthenium(ii) chloride hydrate. La calibration en fonction de l'oxygène a été effectuée et pour le second composé, qui s'est révélé plus performant, les influences de la température, de la salinité et de la pression hydrostatique ont été étudiées