Cyclometalated and NNN Terpyridine Ruthenium Photocatalysts and Their Cytotoxic Activity.

The cyclometalated terpyridine complexes [Ru(η-OAc)(NC-tpy)(PP)] (PP = dppb , (,)-Skewphos , (,)-Skewphos ) are easily obtained from the acetate derivatives [Ru(η-OAc)(PP)] (PP = dppb, (,)-Skewphos , (,)-Skewphos ) and tpy in methanol by elimination of AcOH. The precursors , are prepared from [Ru(η-OAc)(PPh)] and Skewphos in cyclohexane. Conversely, the NNN complexes [Ru(η-OAc)(NNN-tpy)(PP)]OAc (PP = (,)-Skewphos , (,)-Skewphos ) are synthesized in a one pot reaction from [Ru(η-OAc)(PPh)], PP and tpy in methanol.

Terpyridine Diphosphine Ruthenium Complexes as Efficient Photocatalysts for the Transfer Hydrogenation of Carbonyl Compounds.

The cationic achiral and chiral terpyridine diphosphine ruthenium complexes [RuCl(PP)(tpy)]Cl (PP=dppp (1), (R,R)-Skewphos (2) and (S,S)-Skewphos (3)) are easily obtained in 85-88 % yield through a one-pot synthesis from [RuCl (PPh ) ], the diphosphine and 2,2':6',2''-terpyridine (tpy) in 1-butanol. Treatment of 1-3 with NaPF in methanol at RT affords quantitatively the corresponding derivatives [RuCl(PP)(tpy)]PF (PP=dppp (1 a), (R,R)-Skewphos (2 a) and (S,S)-Skewphos (3 a)). Reaction of [RuCl (PPh ) ] with (S,R)-Josiphos or (R)-BINAP in toluene, followed by treatment with tpy in 1-butanol and finally with NaPF in MeOH gives [RuCl(PP)(tpy)]PF (PP=(S,R)-Josiphos (4 a), (R)-BINAP (5 a)) isolated in 78 % and 86 % yield, respectively.

Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells.

The chiral cationic complex [Ru(η -OAc)(CO)((R,R)-Skewphos)(phen)]OAc (2 ), isolated from reaction of [Ru(η -OAc)(η -OAc)(R,R)-Skewphos)(CO)] (1 ) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)-Skewphos)(phen)]Y (X=Y=OPiv 3 ; X=SAc, Y=OAc 4 ). The corresponding enantiomers 2 -4 have been obtained from 1 containing (S,S)-Skewphos. Reaction of 2 and 2 with (S)-cysteine and NaPF at pH=9 gives the diastereoisomers [Ru((S)-Cys)(CO)(PP)(phen)]PF (PP=(R,R)-Skewphos 2 -Cys; (S,S)-Skewphos 2 -Cys).

Preparation of Neutral [Ru(OCR)P(NN)], Cationic [Ru(OCR)P(NN)](OCR) and Pincer [Ru(OCR)(CNN)P] (P = PPh, P = diphosphine) Carboxylate Complexes and their Application in the Catalytic Carbonyl Compounds Reduction.

The diacetate complexes -[Ru(κ-OAc)(PPh)(NN)] (NN = ethylenediamine (en) (), 2-(aminomethyl)pyridine (ampy) (), 2-(aminomethyl)pyrimidine (ampyrim) ()) have been isolated in 76-88% yield by reaction of [Ru(κ-OAc)(PPh)] with the corresponding nitrogen ligands. The ampy-type derivatives and undergo isomerization to the thermodynamically most stable cationic complexes [Ru(κ-OAc)(PPh)(NN)]OAc ( and ) and -[Ru(κ-OAc)(PPh)(NN)] ( and ) in methanol at RT. The -[Ru(κ-OAc)(P)] (P = dppm (), dppe ()) compounds have been synthesized from [Ru(κ-OAc)(PPh)] by reaction with the suitable diphosphine in toluene at 95 °C.

Cationic carboxylate and thioacetate ruthenium(ii) complexes: synthesis and cytotoxic activity against anaplastic thyroid cancer cells.

The cationic acetate ruthenium complex [Ru(η1-OAc)(CO)(dppb)(phen)]OAc (1) is easily prepared in 83% yield from [Ru(η1-OAc)(η2-OAc)(CO)(dppb)] (dppb = 1,4-bis(diphenylphosphino)butane) and 1,10-phenanthroline (phen) in MeOH. The derivative 1 undergoes easy substitution of the coordinated acetate by reaction with NaOPiv, KSAc, and KSCN in MeOH, affording the corresponding complexes [RuX(CO)(dppb)(phen)]X (X = OPiv, 2; SAc, 3; and NCS, 4), whereas its reaction with NaCl and NH4PF6 affords [RuCl(CO)(dppb)(phen)]PF6 (5). Carboxylate complexes 1 and 2 show high solubility in water, enabling easy exchange of the coordinated carboxylate by water and other ligands (CH3CN, glutathione).

CNN pincer ruthenium complexes for efficient transfer hydrogenation of biomass-derived carbonyl compounds.

The ligand HCNNOMe (6-(4-methoxyphenyl)-2-aminomethylpyridine) is easily prepared from the commercially available 6-(4-methoxyphenyl)pyridine-2-carbaldehyde by the reaction of hydroxylamine and hydrogenation (H2, 1 atm) with Pd/C. The pincer complexes cis-[RuCl(CNNOMe)(PPh3)2] (1) and [RuCl(CNNOMe)(PP)] (PP = dppb, 2; and dppf, 3) are synthesized from [RuCl2(PPh3)3], HCNNOMe and PP (for 2 and 3) in 2-propanol with NEt3 at reflux and are isolated in 85-93% yield. Carbonylation of 1 (CO, 1 atm) gives [RuCl(CNNOMe)(CO)(PPh3)] (4) (79% yield) which cleanly reacts with Na[BArf4] and PCy3, affording the cationic trans-[Ru(CNNOMe)(CO)(PCy3)(PPh3)][BArf4] (5) (92% yield).

Preparation of monocarbonyl ruthenium complexes bearing bidentate nitrogen and phosphine ligands and their catalytic activity in carbonyl compound reduction.

Monocarbonyl complexes [RuCl(CO)(PR)(NN)] (R = Cy, NN = en 1, ampy 2; R = iPr; NN = en 3) have been prepared in a one pot reaction from [RuCl(CO)(dmf)(PPh)], PR and the NN ligand in CHCl. Treatment of [Ru(OAc)(CO)(PPh)] with NN ligands in methanol gives the cationic derivatives [Ru(OAc)(CO)(PPh)(NN)]OAc (NN = en 4, ampy 5) in which one acetate acts as a bidentate ligand, whereas the other is not coordinated. Diphosphine complexes [RuCl(CO)(PP)(PPh)] (PP = dppb 6, dppf 7, (R)-BINAP 8, (R,S)-Josiphos 9 and (R,R)-Skewphos 10) have been obtained starting from [RuCl(CO)(dmf)(PPh)] and the PP ligand in CHCl or toluene at reflux.

A specific nanobody prevents amyloidogenesis of D76N β-microglobulin in vitro and modifies its tissue distribution in vivo.

Systemic amyloidosis is caused by misfolding and aggregation of globular proteins in vivo for which effective treatments are urgently needed. Inhibition of protein self-aggregation represents an attractive therapeutic strategy. Studies on the amyloidogenic variant of β-microglobulin, D76N, causing hereditary systemic amyloidosis, have become particularly relevant since fibrils are formed in vitro in physiologically relevant conditions.

Citrate-stabilized gold nanoparticles hinder fibrillogenesis of a pathological variant of β-microglobulin.

Nanoparticles have repeatedly been shown to enhance fibril formation when assayed with amyloidogenic proteins. Recently, however, evidence casting some doubt about the generality of this conclusion started to emerge. Therefore, to investigate further the influence of nanoparticles on the fibrillation process, we used a naturally occurring variant of the paradigmatic amyloidogenic protein β-microglobulin (β2m), namely D76N β2m where asparagine replaces aspartate at position 76.

Functional expression of aryl hydrocarbon receptor on mast cells populating human endometriotic tissues.

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue outside the uterus. A diffuse infiltration of mast cells (MCs) is observed throughout endometriotic lesions, but little is known about how these cells contribute to the network of molecules that modulate the growth of ectopic endometrial implants and promote endometriosis-associated inflammation. The aryl hydrocarbon receptor (AhR), a transcription factor known to respond to environmental toxins and endogenous compounds, is present in MCs.

Thermodynamic temperature assignment to the point of inflection of the melting curve of high-temperature fixed points.

The thermodynamic temperature of the point of inflection of the melting transition of Re-C, Pt-C and Co-C eutectics has been determined to be 2747.84 ± 0.35 K, 2011.

Phospholipid profile of amniotic fluid in ovine model of congenital diaphragmatic hernia (CDH): the effect of fetal tracheal occlusion.

Fetal endoscopic tracheal occlusion has been proposed as a prenatal intervention to ameliorate congenital diaphragmatic hernia (CDH) prognosis. Tracheal occlusion (TO) prevents pulmonary fluid egress, leading to tissue expansion, reversal of lung hypoplasia, and potential maturation. Fetal lung maturity strongly correlates with amniotic fluid (AF) phospholipidic composition.

Congenital pulmonary malformations: metabolomic profile of lung phenotype in infants.

Background: The main hydrosoluble metabolites in three different human congenital pulmonary malformations are described by nuclear magnetic resonance (NMR) spectroscopy.

Methods: Bronchogenic cyst (BC), congenital lobar emphysema (CLE) and intrapulmonary sequestration (IPS), were analyzed with respect to a control sample. The extracted metabolites were submitted to high-resolution (1)H NMR-spectroscopy.

Metabolomic profile of amniotic fluid to evaluate lung maturity: the diaphragmatic hernia lamb model.

Background: Tracheal occlusion (TO) stimulates lung growth in fetuses affected with congenital diaphragmatic hernia (CDH) although the processes involved in lung maturation still remain unknown. The objective of this study was to evaluate the metabolomic profile of amniotic fluid (AF) following TO in fetal lamb model in order to obtain an indirect view of mechanisms involved in pulmonary reversal hypoplasia and biochemical maturity in response to fetal TO.

Methods: Liquid Chromatography Mass Spectrometry was performed on lamb AF samples at: age I (70 days' gestation); age II (102 days' gestation); age III (136 days' gestation).

BMP tests of source selected OFMSW to evaluate anaerobic codigestion with sewage sludge.

The aim of this study is to characterize different types of source selected organic fraction of municipal solid waste (SS-OFMSW) in order to optimize the upgrade of a sewage sludge anaerobic digestion unit by codigestion. Various SS-OFMSW samples were collected from canteens, supermarkets, restaurants, households, fruit-vegetable markets and bakery shops. The substrates characterization was carried out getting traditional chemical-physical parameters, performing elemental analysis and measuring fundamental anaerobic digestion macromolecular compounds such as carbohydrates, proteins, lipids and volatile fatty acids.

Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity.

Photodynamic therapy (PDT) is an emerging cancer treatment modality based on the excitation of a nontoxic photosensitizer with harmless visible light to produce reactive-oxygen species (ROS) that induce apoptosis and/or necrosis in cancer cells. As the efficacy of this therapy strongly depends of the nature of the photosensitizer, there is a great interest to develop new photoactive molecules. Here we report for the first time the synthesis, characterization and bioactivity of metal complexes between the non-aromatic expanded porphyrin, namely 20-[[4'-(Trimethylsilyl)ethoxycarbonyl]phenyl-2,13-dimethyl-3,12-diethyl-[24] iso-pentaphyrin (PCRed) and Zn(II) [Zn(II)-PCRed] or Lu(III) [Lu(III)-PCRed].

New benzo[h]quinoline-based ligands and their pincer Ru and Os complexes for efficient catalytic transfer hydrogenation of carbonyl compounds.

New benzo[h]quinoline ligands (HCN'N) containing a CHRNH2 (R=H (a), Me (b), tBu (c)) function in the 2-position were prepared starting from benzo[h]quinoline N-oxide (in the case of ligand a) and 2-chlorobenzo[h]quinoline (for ligands b and c). These compounds were used to prepare ruthenium and osmium complexes, which are excellent catalysts for the transfer hydrogenation (TH) of ketones. The reaction of a with [RuCl2(PPh3)3] in 2-propanol at reflux afforded the terdentate CN'N complex [RuCl(CN'N)(PPh3)2] (1), whereas the complexes [RuCl(CN'N)(dppb)] (2-4; dppb=Ph2P(CH2)4PPh2) were obtained from [RuCl2(PPh3)(dppb)] with a-c, respectively.

Role of the NH2 functionality and solvent in terdentate CNN alkoxide ruthenium complexes for the fast transfer hydrogenation of ketones in 2-propanol.

The reaction of [RuCl(CNN)(dppb)] (1; HCNN=6-(4-methylphenyl)-2-pyridylmethylamine) with NaOiPr in 2-propanol/C6D6 affords the alcohol adduct alkoxide [Ru(OiPr)(CNN)(dppb)].n iPrOH (5), containing the Ru-NH2 linkage. The alkoxide [Ru(OiPr)(CNN)(dppb)] (4) is formed by treatment of the hydride [Ru(H)(CNN)(dppb)] (2) with acetone in C6D6.

Osmium pyme complexes for fast hydrogenation and asymmetric transfer hydrogenation of ketones.

The osmium compound trans,cis-[OsCl2(PPh3)2(Pyme)] (1) (Pyme=1-(pyridin-2-yl)methanamine), obtained from [OsCl2(PPh3)3] and Pyme, thermally isomerizes to cis,cis-[OsCl2(PPh3)(2)(Pyme)] (2) in mesitylene at 150 degrees C. Reaction of [OsCl2(PPh3)3] with Ph2P(CH2)(4)PPh2 (dppb) and Pyme in mesitylene (150 degrees C, 4 h) leads to a mixture of trans-[OsCl2(dppb)(Pyme)] (3) and cis-[OsCl2(dppb)(Pyme)] (4) in about an 1:3 molar ratio. The complex trans-[OsCl2(dppb)(Pyet)] (5) (Pyet=2-(pyridin-2-yl)ethanamine) is formed by reaction of [OsCl2(PPh3)3] with dppb and Pyet in toluene at reflux.

PNA conjugated to high-molecular weight poly(ethylene glycol): synthesis and properties.

The conjugation of a bioactive, fluorescent PNA sequence to high-molecular weight poly(ethylene glycol) (PEG) is described and the properties of the PEG-PNA conjugate are evaluated.

C-H activation and C=C double bond formation reactions in iridium ortho-methyl arylphosphane complexes.

The Vaska-type iridium(I) complex [IrCl(CO){PPh(2)(2-MeC(6)H(4))}(2)] (1), characterized by an X-ray diffraction study, was obtained from iridium(III) chloride hydrate and PPh(2)(2,6-MeRC(6)H(3)) with R=H in DMF, whereas for R=Me, activation of two ortho-methyl groups resulted in the biscyclometalated iridium(III) compound [IrCl(CO){PPh(2)(2,6-CH(2)MeC(6)H(3))}(2)] (2). Conversely, for R=Me the iridium(I) compound [IrCl(CO){PPh(2)(2,6-Me(2)C(6)H(3))}(2)] (3) can be obtained by treatment of [IrCl(COE)(2)](2) (COE=cyclooctene) with carbon monoxide and the phosphane in acetonitrile. Compound 3 in CH(2)Cl(2) undergoes intramolecular C-H oxidative addition, affording the cyclometalated hydride iridium(III) species [IrHCl(CO){PPh(2)(2,6-CH(2)MeC(6)H(3))}{PPh(2)(2,6-Me(2)C(6)H(3))}] (4).

New MultiPEG-conjugated theophylline derivatives: synthesis and pharmacological evaluations.

The successful conjugation of active theophylline molecules to two new multifunctional high-molecular weight poly(ethylene glycol) derivatives (MultiPEG) and their pharmacokinetic evaluations are reported. The drug loading was increased up to six times in comparison with commercial PEG of the same molecular weight. A clear increase of the time of persistence within the body and a concomitant improvement of the overall pharmacokinetic properties of those prodrugs were also observed.

Antiproliferative activity of a triplex-forming oligonucleotide recognizing a Ki-ras polypurine/polypyrimidine motif correlates with protein binding.

The Ki-ras gene is frequently mutated and/or overexpressed in human cancer. Since it is suspected to play a key role in the pathogenesis of many tumors, there is interest to search for strategies aiming at the specific inhibition of this oncogene. In this paper, we investigated the capacity of a 20 mer G-rich oligonucleotide (ODN20) conjugated to high molecular weight monomethoxy polyethylene glycol (MPEG) to inhibit the expression of the Ki-ras gene and the proliferation of pancreatic cancer cells.

Synthesis of oligonucleotide-peptide PEG-conjugated: the EGG (oligonucleotide)-chicken (peptide) dilemma?

The synthesis of a peptide-PEG-oligonucleotide chimera is compared when starting from the peptide or from the oligonucleotide sequence.