Dinuclear Iron Complexes of Iminopyridine-Based Ligands as Selective Cytotoxins for Tumor Cells and Inhibitors of Cancer Cell Migration.

A family of dinuclear iron (II) compounds with iminopyridine-based ligands displays selective cytotoxic activity against cancer cell lines. All compounds have IC50 values 2-6 fold lower than that of cisplatin, and 30-90 fold lower than that of carboplatin for the tumor cell lines assayed. Comparing the IC50 values between tumor and non-tumor cell lines, the selectivity indexes range from 3.2 to 34, compound 10, [Fe2(4)2(CH3CN)4](BF4)4, showing the highest selectivity. Those compounds carrying substituents on the iminopyridine ring show the same cytotoxicity as those without substituents. However, the electronic effects of the substituents on position 6 may be important for the cytotoxicity of the complexes, and consequently for their selectivity. All compounds act over DNA, promoting cuts on both strands in the presence of reactive oxygen species. Since compound 10 presented the highest selectivity, its cytotoxic effect was further characterized. It induces apoptosis, affects cell cycle phase distribution in a cell-dependent manner, and its cytotoxic effect is linked to reactive oxygen species generation. In addition, it decreases tumor cell migration, showing potential antimetastatic effects. These properties make compound 10 a good lead antitumor agent among all compounds studied here.

Determination of the surface temperature of magnetically heated nanoparticles using a catalytic approach.

Herein we describe a new method for the determination of the surface temperature of magnetically heated nanoparticles in solution using the temperature dependency of the catalytic performances of iron carbide nanoparticles coated with ruthenium (Fe2.2C@Ru) for acetophenone hydrodeoxygenation. A correlation between nanoparticle surface temperature and magnetic field could be established. Very high surface temperatures could be estimated in different solvents, which were also found similar at a given magnetic field and well above some solvent boiling points.

σ-H-H, σ-C-H, and σ-Si-H Bond Activation Catalyzed by Metal Nanoparticles.

Activation of H-H, Si-H, and C-H bonds through σ-bond coordination has grown in the past 30 years from a scientific curiosity to an important tool in the functionalization of hydrocarbons. Several mechanisms were discovered via which the initially σ-bonded substrate could be converted: oxidative addition, heterolytic cleavage, σ-bond metathesis, electrophilic attack, etc. The use of metal nanoparticles (NPs) in this area is a more recent development, but obviously nanoparticles offer a much richer basis than classical homogeneous and heterogeneous catalysts for tuning reactivity for such a demanding process as C-H functionalization. Here, we will review the surface chemistry of nanoparticles and catalytic reactions occurring in the liquid phase, catalyzed by either colloidal or supported metal NPs. We consider nanoparticles prepared in solution, which are stabilized and tuned by polymers, ligands, and supports. The question we have addressed concerns the differences and similarities between molecular complexes and metal NPs in their reactivity toward σ-bond activation and functionalization.

Hydrodeoxygenation Using Magnetic Induction: High-Temperature Heterogeneous Catalysis in Solution.

Magnetic heating has recently been demonstrated as an efficient way to perform catalytic reactions after deposition of the heating agent and the catalyst on a support. Here we show that in solution, and under mild conditions of mean temperature and pressure, it is possible to use magnetic heating to carry out transformations that are otherwise performed heterogeneously at high pressure and/or high temperature. As a proof of concept, we chose the hydrodeoxygenation of acetophenone derivatives and of biomass-derived molecules, namely furfural and hydroxymethylfurfural. These reactions are difficult, require heterogeneous catalysts and high pressures, and, to the best of our knowledge, have no precedent in standard solution. Here, hydrodeoxygenations are fully selective under mild conditions (3 bar H2 , moderate mean temperature of the solvent). The reason for this reactivity is the fast heating of the particles well above the boiling temperature of the solvent and the local creation of hot spots surrounded by a vapor layer, in which high temperature and pressure may be present. This technology may be practicable for many organic transformations.

Halogen bonding effects on the outcome of reactions at metal centres.

Key findings regarding the effects of ligand preorganisation via halogen bonding on the outcome of reactions at rhodium are reported. An unprecedented halogen bonding-mediated oxidative addition of CAr-I bonds to rhodium with efficient formation of cyclometallated species deserves special mention.

[Withdrawal of chronic mechanical ventilation at home: coordination, organisation and implementation]. / Beëindiging van chronische beademing in de thuissituatie.

In the Netherlands, an increasing number of patients are dependent on domiciliary ventilation. General practitioners and elderly care physicians caring for these patients are increasingly confronted with problems related to chronic ventilation. Most patients die due to progression of respiratory failure, however, patients may ask their physician to electively withdraw their assisted ventilation. According to the Dutch Medical Treatment Contracts Act, withdrawal of domiciliary ventilation at the request of a patient constitutes normal medical care and concerns neither the assessment of, nor the compliance with, a request for euthanasia. Currently, there is no Dutch guidance or guideline containing practical advice regarding the medical, ethical, organisational and supportive aspects of withdrawal of domiciliary ventilation. This paper addresses the planning necessary for the patient and between treating professionals, for the organisation and implementation of withdrawal of domiciliary ventilation at the patient's home, a nursing home or hospice.

Ruthenium nanoparticles ligated by cholesterol-derived NHCs and their application in the hydrogenation of arenes.

Herein we present ruthenium nanoparticles (Ru-NPs) stabilized with two rigid NHC ligands derived from cholesterol. The obtained nanoparticles were fully characterized and applied in the hydrogenation of various aromatic compounds under mild conditions. Interestingly, the more bulky ligand gives a slightly lower ligand coverage and a faster catalyst.

XBphos-Rh: a halogen-bond assembled supramolecular catalyst.

The use of halogen bonding as a tool to construct a catalyst backbone is reported. Specifically, pyridyl- and iodotetrafluoroaryl-substituted phosphines were assembled in the presence of a rhodium(i) precursor to form the corresponding halogen-bonded complex XBphos-Rh. The presence of fluorine substituents at the iodo-containing supramolecular motif was not necessary for halogen bonding to occur due to the template effect exerted by the rhodium center during formation of the halogen-bonded complex. The halogen-bonded supramolecular complexes were successfully tested in the catalytic hydroboration of terminal alkynes.

A protic ionic liquid as an atom economical solution for palladium catalyzed asymmetric allylic alkylation.

The asymmetric allylic alkylation of rac-1,3-diphenyl-3-acetoxyprop-1-ene (I) catalysed by palladium and diverse phosphorus containing ligands [(S)-BINAP, (R,R)-Chiraphite and (R,R)-Et-Duphos] in an ionic liquid [HDBU][OAc] was successfully performed, achieving full conversions and up to 96% ee of the (S)-product when (R,R)-Et-Duphos was used as a ligand. The reaction could be performed using an equimolar amount of substrate, malonate and base DBU, in which case the total products sum to the desired alkylated product and the ionic pair [HDBU][OAc]; this system thus produces its own IL solvent as the only co-product. These catalytic systems were active in recycling experiments for up to four cycles, albeit with a loss of activity due to the poor retention of palladium in the ionic liquid. The catalytic performance of each Pd/ligand system was optimized by varying the ratio of the substrate and malonate. Systems based on [HDBU][OAc] were found to be the best.

Characterization of secondary phosphine oxide ligands on the surface of iridium nanoparticles.

The synthesis of iridium nanoparticles (IrNPs) ligated by various secondary phosphine oxides (SPOs) is described. This highly reproducible and simple method via H2 reduction produces well dispersed, small nanoparticles (NPs), which were characterized by the state-of-the-art techniques, such as TEM, HRTEM, WAXS and ATR FT-IR spectroscopy. In particular, multinuclear solid state MAS-NMR spectroscopy with and without cross polarization (CP) enabled us to investigate the different binding modes adopted by the ligand at the nanoparticle surface, suggesting the presence of three possible types of coordination: as a purely anionic ligand Ir-P(O)R2, as a neutral acid R2P-O-H and as a monoanionic bidentate H-bonded dimer R2P-O-HO[double bond, length as m-dash]PR2. Specifically, the higher basicity of the dicyclohexyl system leads to the formation of IrNPs in which the bidentate binding mode is most abundant. Such cyclohexyl groups are bent towards the edges, as is suggested by the study of 13CO coordination on the NP surface. This study also showed that the number of surface sites on faces available for bridging CO molecules is higher than the number of sites for terminal CO species on edges and apices, which is unexpected taking into account the small size of the nanoparticles. In addition, the IrNPs present a high chemoselectivity in the hydrogenation of cinnamaldehyde to the unsaturated alcohol.

Soluble Platinum Nanoparticles Ligated by Long-Chain N-Heterocyclic Carbenes as Catalysts.

Soluble platinum nanoparticles (Pt NPs) ligated by two different long-chain N-heterocyclic carbenes (LC-IPr and LC-IMe) were synthesized and fully characterized by TEM, high-resolution TEM, wide-angle X-ray scattering (WAXS), X-ray photoelectron spectroscopy (XPS), and solution NMR. The surface chemistry of these NPs (Pt@LC-IPr and Pt@LC-IMe) was investigated by FT-IR and solid state NMR using CO as a probe molecule. A clear influence of the bulkiness of the N-substituents on the size, surface state, and catalytic activity of these Pt NPs was observed. While Pt@LC-IMe showed no activity in the hydroboration of phenylacetylene, Pt@LC-IPr revealed good selectivity for the trans-isomer, which may be supported by a homogeneous species. This is the first example of hydroboration of acetylenes catalyzed by non-supported Pt NPs.

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.

Phosphine Supported Ruthenium Nanoparticle Catalyzed Synthesis of Substituted Pyrazines and Imidazoles from α-Diketones.

A new methodology has been developed for the synthesis of highly substituted nitrogen heterocycles such as pyrazines and imidazoles starting from α-diketones using phosphine supported ruthenium nanoparticles (RuNPs) as catalysts. Ruthenium nanoparticles Ru1-Ru4 supported with different phosphines such as dbdocphos, dppp, DPEphos, and Xantphos are screened, of which Ru1 and Ru4 are found to be the most active. Interestingly, aryl-substituted and alkyl-substituted α-diketones produced different products: namely, pyrazine and imidazoles, respectively. This reaction methodology has been applied to the synthesis of a key intermediate (2m) of the marine cytotoxic natural product Dragmacidin B and an estrogen receptor (2l). This work represents the first examples of pyrazines prepared by RuNPs.

Iridium versus Iridium: Nanocluster and Monometallic Catalysts Carrying the Same Ligand Behave Differently.

A specific secondary phosphine oxide (SPO) ligand (tert-butyl(phenyl)phosphine oxide) was employed to generate two iridium catalysts, an Ir-SPO complex and IrNPs (iridium nanoparticles) ligated with SPO ligands, which were compared mutually and with several supported iridium catalysts with the aim to establish the differences in their catalytic properties. The Ir-SPO-based catalysts showed totally different activities and selectivities in the hydrogenation of various substituted aldehydes, in which H2 is likely cleaved by a metal-ligand cooperation, that is, the SPO ligand and a neighboring metal centre operate in tandem to activate the hydrogen molecule. In addition, the supported IrNPs behave very differently from both Ir-SPO catalysts. This study exemplifies perfectly the advantages and disadvantages related to the use of the main types of catalysts, and thus the dissimilarities between them.

Correlation between the Selectivity and the Structure of an Asymmetric Catalyst Built on a Chirally Amplified Supramolecular Helical Scaffold.

For the first time, supramolecular helical rods composed of an achiral metal complex and a complementary enantiopure monomer provided a good level of enantioinduction in asymmetric catalysis. Mixtures containing an achiral ligand monomer (BTA(PPh2), 2 mol %) and an enantiopure ligand-free comonomer (ester BTA, 2.5 mol %), both possessing a complementary benzene-1,3,5-tricarboxamide (BTA) central unit, were investigated in combination with [Rh(cod)2]BArF (1 mol %) in the asymmetric hydrogenation of dimethyl itaconate. Notably, efficient chirality transfer occurs within the hydrogen-bonded coassemblies formed by BTA Ile and the intrinsically achiral catalytic rhodium catalyst, providing the hydrogenation product with up to 85% ee. The effect of the relative content of BTA Ile as compared to the ligand was investigated. The amount of chiral comonomer can be decreased down to one-fourth of that of the ligand without deteriorating the enantioselectivity of the reaction, while the enantioselectivity decreases for mixtures containing high amounts of BTA Ile. The nonlinear relationship between the amount of chiral comonomer and the enantioselectivity indicates that chirality amplification effects are at work in this catalytic system. Also, right-handed helical rods are formed upon co-assembly of the achiral rhodium complex of BTA(PPh2) and the enantiopure comonomer BTA Ile as confirmed by various spectroscopic and scattering techniques. Remarkably, the major enantiomer and the selectivity of the catalytic reaction are related to the handedness and the net helicity of the coassemblies, respectively. Further development of this class of catalysts built on chirally amplified helical scaffolds should contribute to the design of asymmetric catalysts operating with low amounts of chiral entities.

Novel iminopyridine derivatives: ligands for preparation of Fe(ii) and Cu(ii) dinuclear complexes.

A series of imino- and amino-pyridine ligands based on dihydrobenzofurobenzofuran (BFBF) and methanodibenzodioxocine (DBDOC) backbones have been synthesized. These ligands form exclusively dinuclear complexes with metals such as iron(II) and copper(II). The structures for complexes 15, 16, 18, 19, 20, 21, 23, and 24 were determined by X-ray crystallography. The complexes show large distances for the metal nuclei and different geometries depending on the nature of the metal. An octahedral geometry was observed for the iron(II) complexes, while copper(II) complex 24 showed a distorted trigonal bipyramidal geometry. The iron(II) complexes showed activity as catalysts in the cycloaddition of CO2 to epoxides, obtaining moderate yields of cyclic carbonates.

Air-Stable Gold Nanoparticles Ligated by Secondary Phosphine Oxides as Catalyst for the Chemoselective Hydrogenation of Substituted Aldehydes: a Remarkable Ligand Effect.

Air-stable and homogeneous gold nanoparticles (AuNPs, 1a-5a) ligated by various secondary phosphine oxides (SPOs), [R(1)R(2)P(O)H] (R(1) = Naph, R(2) = (t)Bu, L1; R(1) = R(2) = Ph, L2; R(1) = Ph, R(2) = Naph, L3; R(1) = R(2) = Et, L4; R(1) = R(2) = Cy, L5; R(1) = R(2) = (t)Bu, L6), with different electronic and steric properties were synthesized via NaBH4 reduction of the corresponding Au(I)-SPO complex. These easily accessible ligands allow the formation of well dispersed and small nanoparticles (size 1.2-2.2 nm), which were characterized by the use of a wide variety of techniques, such as transmission electron microscopy, thermogravimetric analysis, UV-vis, energy-dispersive X-ray, X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR FT-IR), and cross polarization magic angle spinning (CP MAS) NMR spectroscopy. A pronounced ligand effect was found, and CP MAS NMR experiments enabled us to probe important differences in the polarity of the P-O bond of the SPOs coordinated to the nanoparticle surface depending on the type of substituents in the ligand. AuNPs containing aryl SPOs carry only SPO anions and are highly selective for aldehyde hydrogenation. AuNPs of similar size made with alkyl SPOs contain also SPOH, hydrogen bonded to SPO anions. As a consequence they contain less Au(I) and more Au(0), as is also evidenced by XPS. They are less selective and active in aldehyde hydrogenation and now show the typical activity of Au(0)NPs in nitro group hydrogenation.

Phosphinothiolates as ligands for polyhydrido copper nanoclusters.

The reaction of [CuI(HSC6 H4 PPh2 )]2 with NaBH4 in CH2 Cl2 /EtOH led to air- and moisture-stable copper hydride nanoparticles (CuNPs) containing phosphinothiolates as new ligands, one of which was isolated by crystallization. The X-ray crystal structure of [Cu18 H7 L10 I] (L=(-) S(C6 H4 )PPh2 ) shows unprecedented features in its 28-atom framework (18 Cu and 10 S atoms). Seven hydrogen atoms, in hydride form, are needed for charge balance and were located by density functional theory methods. H2 was released from the copper hydride nanoparticles by thermolysis and visible light irradiation.

Air-stable gold nanoparticles ligated by secondary phosphine oxides for the chemoselective hydrogenation of aldehydes: crucial role of the ligand.

The synthesis of air-stable and homogeneous gold nanoparticles (AuNPs) employing tert-butyl(naphthalen-1-yl)phosphine oxide as supporting ligand is described via NaBH4 reduction of a Au(I) precursor, [(tert-butyl(naphthalen-1-yl)phosphine oxide)AuCl]2. This highly reproducible and simple procedure furnishes small (1.24 ± 0.16 nm), highly soluble nanoparticles that are found to be highly active catalysts for the hydrogenation of substituted aldehydes, giving high conversions and chemoselectivities for a wide variety of substrates. In addition to catalytic studies the role of the novel stabilizer in the remarkable activity and selectivity exhibited by this system was interrogated thoroughly using a wide range of techniques, including ATR FT-IR, HRMAS NMR, XPS, and EDX spectroscopy. In particular, isotopic labeling experiments enabled us to probe the coordination mode adopted by the SPO ligand bound to the nanoparticle surface by ATR FT-IR spectroscopy. In combination with a series of control experiments we speculate that the SPO ligand demonstrates ligand-metal cooperative effects and plays a seminal role in the heterolytic hydrogenation mechanism.

Supramolecular catalysis. Part 2: artificial enzyme mimics.

The design of artificial catalysts able to compete with the catalytic proficiency of enzymes is an intense subject of research. Non-covalent interactions are thought to be involved in several properties of enzymatic catalysis, notably (i) the confinement of the substrates and the active site within a catalytic pocket, (ii) the creation of a hydrophobic pocket in water, (iii) self-replication properties and (iv) allosteric properties. The origins of the enhanced rates and high catalytic selectivities associated with these properties are still a matter of debate. Stabilisation of the transition state and favourable conformations of the active site and the product(s) are probably part of the answer. We present here artificial catalysts and biomacromolecule hybrid catalysts which constitute good models towards the development of truly competitive artificial enzymes.