Reversible Single-Electron-Transfer to Oxygen in a Stable N-Heterocyclic Carbene Palladium(I) Metalloradical.

The chemical and electrochemical one-electron oxidation of [Pd(IPr)2] (1) leads to the formation of mononuclear palladium(I) complex [Pd(IPr)2][PF6] (2). This bench-stable metalloradical has been fully characterized and its structure confirmed by X-ray diffraction analysis. EPR and DFT studies confirm the localization of the unpaired electron onto the metal center. Low temperature NMR and EPR measurements reveal the ability of complex 2 to reversibly coordinate and reduce the dioxygen molecule, leading to the formation of a three-coordinate complex, [PdII(IPr)2(η1-O2)]+ (4), in which the unpaired electron has been transferred to the superoxido ligand.

Water-soluble platinum nanoparticles stabilized by sulfonated N-heterocyclic carbenes: influence of the synthetic approach.

The synthesis of metal nanoparticles (NPs) under controlled conditions in water remains a challenge in nanochemistry. Two different approaches to obtain platinum NPs, which involve the treatment of aqueous solutions of preformed sulfonated (NHC)Pt(ii) dimethyl complexes with carbon monoxide, and of (NHC)Pt(0) diolefin complexes with dihydrogen (NHC = N-heterocyclic carbene), are disclosed here. The resulting NPs were found to be highly stable in water under air for an indefinite time period. Coordination of the NHC ligands to the platinum surface via the carbenic carbon was monitored by solid-state NMR spectroscopy, and the presence of a platinum-carbon bond was unambiguously evidenced by the determination of a 13C-195Pt coupling constant (1106 and 1050 Hz for NPs containing 13C labeled-NHC ligands and prepared under CO and H2, respectively). The coordination of CO to the (NHC)Pt(ii) precursors prior to formation of the NPs was confirmed by NMR spectroscopy. When using a disulfonated NHC ligand, a second coordination sphere containing bis(NHC)Pt(ii) complexes is described. Under CO, the formation of NPs was found to be slower than in a previously reported thermal method (Angew. Chem., Int. Ed., 2014, 53, 13220-13224), but led to NPs of similar sizes, whereas under H2, the synthesis of platinum NPs progressed even more slowly and produced larger NPs. In addition to the influence of the synthetic approach, the present study highlights the importance of ligand design for NP stabilization.

Synthesis of Water-Soluble Palladium Nanoparticles Stabilized by Sulfonated N-Heterocyclic Carbenes.

A strategy involving the decomposition of palladium(II) organometallic complexes with sulfonated N-heterocyclic carbene ligands leads to the formation of stable and water-soluble Pd nanoparticles. Three different methodologies (thermal decomposition, reduction under 13 CO atmosphere, and reduction with H2 ) gave particles with different shapes and sizes, ranging from 1.5 to 7 nm. The structures of the organometallic intermediates and organic decomposition products were elucidated by NMR spectroscopy. To check the accessibility of the surface, the nanoparticles were tested as catalysts for the chemoselective hydrogenation of styrene in water. An effect of the particle size on the catalyst activity was observed. The aqueous phase was recycled up to ten times without any precipitation of metallic palladium.

Monitoring of nanoparticle reactivity in solution: interaction of l-lysine and Ru nanoparticles probed by chemical shift perturbation parallels regioselective H/D exchange.

Thanks to new water-soluble Ru nanoparticles (NPs) stabilized by sulfonated NHC ligands, we demonstrate that it is possible to monitor the catalyst/substrate interaction using NMR chemical shift perturbations (CSPs), under conditions that closely resemble those applied during the enantiospecific C-H deuteration of l-lysine. Correlating the pH dependence of the interaction of l-lysine with the surface of the RuNPs and its subsequent deuteration, our study underscores the importance of oriented binding to the surface as a critical factor for H/D exchange.

Synthesis of water-soluble palladium(ii) complexes with N-heterocyclic carbene chelate ligands and their use in the aerobic oxidation of 1-phenylethanol.

The synthesis of palladium(ii) complexes containing N-heterocyclic carbene chelate ligands is reported. These chelate ligands have methylene or ethylene ring bridges and sulfonate, carbonate or ammonium functionalities to render the complexes soluble in water. Bis- [(bis-NHC)PdX2] (X = Cl, Br or I) and tetra-carbene [(bis-NHC)2Pd] complexes have been prepared and the crystal structures of two of them have been determined. The NHC ligand is coordinated to the metal center in normal (C2-bound) or abnormal (C4-bound) mode. Processes involving the formation of NHC-Pd bonds or the transfer of NHC ligands have been explored in water. The behavior of the bis-carbene complexes as catalysts for the aerobic oxidation of 1-phenylethanol is also discussed.

Knight Shift in 13 C†NMR Resonances Confirms the Coordination of N-Heterocyclic Carbene Ligands to Water-Soluble Palladium Nanoparticles.

The coordination of N-heterocyclic carbene (NHC) ligands to the surface of 3.7 nm palladium nanoparticles (PdNPs) can be unambiguously established by observation of Knight shift (KS) in the 13 C resonance of the carbenic carbon. In order to validate this coordination, PdNPs with sizes ranging from 1.3 to 4.8 nm were prepared by thermal decomposition or reduction with CO of a dimethyl NHC PdII complex. NMR studies after 13 CO adsorption established that the KS shifts the 13 C resonances of the chemisorbed molecules several hundreds of ppm to high frequencies only when the particle exceeds a critical size of around 2 nm. Finally, the resonance of a carbenic carbon is reported to be Knight-shifted to 600 ppm for 13 C-labelled NHCs bound to PdNPs of 3.7 nm. The observation of these very broad KS resonances was facilitated by using Car-Purcell-Meiboom-Gill (CPMG) echo train acquisition NMR experiments.

Magnetically recoverable catalysts based on mono- or bis-(NHC) complexes of palladium for the Suzuki-Miyaura reaction in aqueous media: two NHC-Pd linkages are better than one.

Pre-synthesized mono- and bis(NHC) palladium complexes have been grafted onto magnetic core/shell γ-Fe2O3/silica particles and tested as catalysts in model Suzuki-Miyaura coupling reactions. The bis(NHC) immobilized complex was found to be a robust catalyst that can operate under mild conditions in aqueous media, even for the activation of chloroarene, whereas the mono(NHC) counterpart rapidly deactivates. Moreover, it can be readily recovered by magnetic separation and reused many times, providing very high productivities, and with so low leaching of palladium that the crude products obtained contain ≤10 ppm Pd.

Poly(benzyl ether) Dendrimers Functionalized at the Core with Palladium Bis(N-Heterocyclic Carbene) Complexes as Catalysts for the Heck Coupling Reaction.

Bis(imidazolylidene)palladium complexes 9-12 containing a sterically hindered aryl group (mesityl or 2,6-diisopropylphenyl) and a poly(benzyl ether) dendron as N-substituents of the NHC ligand are accessible up to the third generation by transmetalation of the corresponding silver complexes. Complexes 9-12 are soluble, active, and very stable catalysts under Heck reaction conditions. The NHC ligand appears to be stably coordinated to the Pd during catalysis. The catalytic activity increases with generation number, although irregularly. The palladium site is not significantly congested in the reaction solvent by the increasing size of the dendritic substituents, as corroborated by X-ray diffraction, fluorescence and DOSY-NMR spectroscopy, and MD simulation studies. This is a consequence of the conformational semiflexibility of the poly(benzyl ether) dendrons and the benzylic link between these dendrons and the N-heterocyclic ligands.

Synthesis and behavior of novel sulfonated water-soluble N-heterocyclic carbene (η(4)-diene) platinum(0) complexes.

A series of water-soluble (NHC)Pt(0)(dvtms) and (NHC)Pt(0)(AE) complexes containing different sulfonated NHC ligands (dvtms = divinyltetramethyldisiloxane and AE = diallyl ether) are reported. The dvtms compounds have been found to be quite robust and to display some conformational rigidity, whereas their AE counterparts are less stable and more flexible. The catalytic evaluation of these complexes in the hydrosilylation of alkynes in water revealed no benefits in favor of the complexes containing the more labile spectator diene (AE), and a fairly regular catalytic behavior for all complexes that restricts the location of the sulfonate group to the proximity of the metal site.

Highly stable water-soluble platinum nanoparticles stabilized by hydrophilic N-heterocyclic carbenes.

Controlling the synthesis of stable metal nanoparticles in water is a current challenge in nanochemistry. The strategy presented herein uses sulfonated N-heterocyclic carbene (NHC) ligands to stabilize platinum nanoparticles (PtNPs) in water, under air, for an indefinite time period. The particles were prepared by thermal decomposition of a preformed molecular Pt complex containing the NHC ligand and were then purified by dialysis and characterized by TEM, high-resolution TEM, and spectroscopic techniques. Solid-state NMR studies showed coordination of the carbene ligands to the nanoparticle surface and allowed the determination of a (13)C-(195)Pt coupling constant for the first time in a nanosystem (940 Hz). Additionally, in one case a novel structure was formed in which platinum(II) NHC complexes form a second coordination sphere around the nanoparticle.

Re-treatment with highly purified nIFNα in Mexican nonresponder patients with chronic genotype 1 hepatitis C.

BACKGROUND AND AIMS: We undertook this study to evaluate the virological response to and presence of adverse events to natural interferon α (nIFNα; Multiferon®) treatment in previously nonresponsive Mexican patients chronically infected with genotype 1 hepatitis C. METHODS: Thirty-nine patients received a 4-week induction of 5 days/week of 6 MU nIFNα plus weight-based ribavirin followed by 3 MU of nIFNα three times a week for 44 weeks. The relationship between viral response and incidence of adverse events was analyzed. RESULTS: Early viral response (EVR) was age- and sex-dependent, with older male patients being less responsive. Sustained viral response (SVR) was evaluated according to: a) intention to treat analysis, b) 48-week treatment and 24-week follow-up (16 patients), and c) patients with EVR (11 patients). None of the factors was significantly different in groups a) and b); however, in group c) there was a better response with a marked viral load decline in younger patients and in patients aged 50 years and older. Five of 39 (13%) patients who completed treatment presented with an SVR. The most common adverse effect was asthenia in 27% of patients. CONCLUSIONS: nIFNα could be a useful strategy for re-treatment in chronic hepatitis C, genotype 1, in previously nonresponsive patients. Confirmation of these data in a larger population is required.

Mechanistic studies on the Pd-catalyzed vinylation of aryl halides with vinylalkoxysilanes in water: the effect of the solvent and NaOH promoter.

The mechanism of the Pd-catalyzed vinylation of aryl halides with vinylalkoxysilanes in water has been studied using different catalytic precursors. The NaOH promoter converts the initial vinylalkoxysilane into a highly reactive water-soluble vinylsilanolate species. Similarly, deuterium-labeling experiments have shown that, irrespective of the catalytic precursor used, vinylation occurs exclusively at the CH vinylic functionality via a Heck reaction and not at the C-Si bond via a Hiyama cross-coupling. The involvement of a Heck mechanism is interpreted in terms of the reduced nucleophilicity of the base in water, which disfavors the transmetalation step. The Heck product (ß-silylvinylarene) undergoes partial desilylation, with formation of a vinylarene, by three different routes: (a) hydrolytic desilylation by the aqueous solvent (only at high temperature); (b) transmetalation of the silyl olefin on the PdH Heck intermediate followed by reductive elimination of vinylarene; (c) reinsertion of the silyl olefin into the PdH bond of the Heck intermediate followed by ß-Si syn-elimination. Both the Hiyama and Heck catalytic cycles and desilylation mechanisms b and c have been computationally evaluated for the [Pd(en)Cl2] precursor in water as solvent. The calculated Gibbs energy barriers support the reinsertion route proposed on the basis of the experimental results.

Dendrimer-encapsulated Pd nanoparticles versus palladium acetate as catalytic precursors in the stille reaction in water.

The performance of several palladium precatalysts, namely, palladium(II) acetate, palladium(0) nanoparticles encapsulated into poly(amidoamine) (PAMAM) dendrimers (Pd DENs), and palladium(II)-PAMAM complexes, in the Stille reaction between trichloro(phenyl)stannane and iodoarenes in water is compared. The reactivity of Pd DENs is similar or inferior to that of palladium(II) acetate, although the presence of the dendrimer suppresses the formation of homocoupling products and allows catalyst recycling. It is suggested that the reaction catalyzed by Pd DENs occurs via palladium species which are leached from the nanoparticle but which remain coordinated to the dendritic macromolecule.

On the Pd-catalyzed vinylation of aryl halides with tris(alkoxy)vinylsilanes in water.

Pd-catalyzed vinylation of aryl halides with tris(alkoxy)vinylsilanes occurs in aqueous NaOH solution through Heck coupling of the aryl halide with the silyl olefin followed by desilylation at the Pd center or, at high temperatures, hydrolysis of the C-Si bond. Pd-mediated desilylation does not occur via beta-Si elimination under these conditions.

Dendronized scorpionate complexes of molybdenum in low and high oxidation states.

Tridentate (L(3)) and bidentate (L(2)) poly(pyrazolyl)methane ligands (Gn-dend)OCH(2)C(pz)(3) (1-4) and (Gn-dend)CH(3,5-Me(2)pz)(2) (pz = pyrazol-1-yl) have been used to synthesize the molybdenum(0) complexes [Mo(CO)(3)(L(3))] (G0-G3, 5-8), [Mo(CO)(4)(L(2))] (G0-G1, 13-14), and [Mo(CO)(3)(NCMe)(L(2))] (G0, 15), and the molybdenum(VI) complexes [MoCl(2)O(2)(L(2))] (9-12). The G0-G3 prefixes represent the generation of poly(aryl ether) dendrons in which the metal complexes are embedded. The molecular structures of compounds 13 and 15 have been determined by X-ray diffraction studies and the hydrodynamic radii of tricarbonyl complexes 5-8 calculated by diffusion-ordered NMR spectroscopy (DOSY). Molybdenum(VI) compounds 9-12 have also been evaluated as catalysts for olefin epoxidation, showing comparable but inferior performances than ligand-free MoCl(2)O(2), probably because of the labile coordination of L(2).

Consecutive palladium-catalyzed Hiyama-Heck reactions in aqueous media under ligand-free conditions.

Symmetric and asymmetric (E)-1,2-diarylethenes are synthesized from aryl bromides by consecutive one-pot Hiyama-Heck reactions carried out in water and under air; the only additives required are sodium hydroxide, palladium acetate and poly(ethylene glycol), and the products are isolable in many cases by simple filtration of the water solution.

Crystal structures of poly(aryl ether) dendrons with palladium scorpionate complexes at their focal point.

Novel palladium(II) complexes with bis(pyrazol-1-yl)methane ligands at the focal point of G0-G3 poly(aryl ether) Fréchet-type dendrons are reported. The molecular structures of the metallodendrimer series G0, G1, and G2 [(dend)CH(3,5-Me2pz)2(PdCl2)] have been determined by X-ray diffraction methods. The three structures show a similar three-dimensional organization of the metal complex, which is progressively engulfed by the branches with increasing dendrimer generation.

Water-soluble carbosilane dendrimers: synthesis biocompatibility and complexation with oligonucleotides; evaluation for medical applications.

Novel amine- or ammonium-terminated carbosilane dendrimers of type nG-[Si{OCH2(C6H3)-3,5-(OCH2CH2NMe2)2}]x, nG-[Si{O(CH2)2N(Me)(CH2)2NMe2}]x and nG-[Si{(CH2)3NH2}]x or nG-[Si{OCH2(C6H3)-3,5-(OCH2CH2NMe3 +I-)2}]x, nG-[Si{O(CH2)2N(Me)(CH2)2NMe3 +I-}]x, and nG-[Si{(CH2)3NH3 +Cl-}]x have been synthesized and characterized up to the third generation by two strategies: 1) alcoholysis of Si--Cl bonds with amino alcohols and subsequent quaternization with MeI, and 2) hydrosilylation of allylamine with Si--H bonds of the dendritic systems and subsequent quaternization with HCl. Quaternized carbosilane dendrimers are soluble in water, although degradation is apparent due to hydrolysis of Si--O bonds. However, dendrimers containing Si--C bonds are water-stable. The biocompatibility of the second-generation dendrimers in primary cell cultures of peripheral blood mononuclear cells (PBMCs) and erythrocytes have been analyzed, and they show good toxicity profiles over extended periods. In addition, we describe a study on the interactions between the different carbosilane dendrimers and DNA oligodeoxynucleotides (ODNs) and plasmids along with a comparative analysis of their toxicity. They can form complexes with DNA ODNs and plasmids at biocompatible doses via electrostatic interaction. Also a preliminary transfection assay has been accomplished. These results demonstrate that the new ammonium-terminated carbosilane dendrimers are good base molecules to be considered for biomedical applications.

Synthesis and 1H NMR studies of paramagnetic nickel(II) complexes containing bis(pyrazolyl)methane ligands with dendritic substituents.

The substituted bis(pyrazolyl)methane ligands RCH(3,5-Me2pz)2(R=SiMe3, CH2Ph, G1, G2, and G3; Gn=Fréchet-type dendritic wedges of generation n) have been prepared starting from H2C(3,5-Me2pz)2. Reaction of these didentate ligands with [NiBr2(DME)] is a straightforward procedure that allows the synthesis of the nickel(II) complexes [NiBr2{RCH(3,5-Me2pz)2}]. The molecular structure of compound (R=CH2Ph) has been determined by X-ray diffraction studies. The nickel centre coordinates two bromine and two nitrogen atoms in a tetrahedral environment, and the metallacycle Ni(NN)2C adopts a boat conformation with the benzyl group in an axial position. 1H NMR studies have been carried out to characterize these paramagnetic nickel compounds in solution. Valuable information about the disposition of the ligands and dendritic wedges in solution has been obtained thanks to the influence of the paramagnetic centre on the proton resonances.

C-C coupling reactions of aryl bromides and arylsiloxanes in water catalyzed by palladium complexes of phosphanes modified with crown ethers.

[reaction: see text] The complexes [PdCl2L2], where L is a crown-ether-containing triarylphosphane, catalyze the formation of biaryls from arylsiloxanes and aryl bromides with high yields in water as solvent and under air. The water-insoluble catalysts [PdCl2(PhCN)2] and [PdCl2(PPh3)2] are also efficient, although they decompose more quickly to form black Pd0.