Synthesis and reactivity of new silyl-substituted monocyclopentadienyl molybdenum and tungsten complexes

The functionalized silylated cyclopentadienyl molybdenum and tungsten complexes [MCpCl(CO)3H] (M=Mo, W; CpCl=η5-C5H4SiMe2Cl) are prepared easily from the reaction of [M(CO)3(NCMe)3] with C5H5SiMe2Cl in refluxing THF, via C–H activation and H transfer to the metal centre. Metathetical replacement of hydride by chloride is readily achieved when their methylene chloride solutions are treated with a few milliliters of CCl4 to give the chloro complexes [MCpCl(CO)3Cl] (M=Mo, W). The chloro–molybdenum complexes react with 1/2 equivalent of deoxygenated water to give the corresponding dinuclear complexes [{Mo(CO)3X}2(μ-CpOCp)], (X=H, Cl; CpOCp=η5-C5H4-SiMe2-O-SiMe2-η5-C5H4), whereas their reaction with one equivalent of anhydrous LiOH in toluene leads to selective substitution of the silicon-bonded chlorine atom to give the hydroxo complexes [MoCpOH(CO)3X] (X=H, Cl; CpOH=η5-C5H4SiMe2OH). These hydroxosilyl complexes can be transformed into the dinuclear compounds [{Mo(CO)3X}2(μ-CpOCp)] by heating (50°C, 2 h) or by their reaction with one equivalent of the respective hydrido and chloro derivatives [MoCpCl(CO)3X]. Total decarbonylation of the hydrido compounds results from oxidation with a stoichiometric amount of PCl5 to give the paramagnetic molybdenum(V) and tungsten(V) complexes [MCpClCl4] (M=Mo, W). Reactions of these complexes with one equivalent of NH2R in the presence of NEt3 yield the imido derivatives [MCpCl(NR)Cl2] (M=Mo, R=2,6-Me2-Ph; M=W, R=tBu) and subsequent oxidation of the tungsten complex with 1/2 equivalent of PCl5 gives [WCpCl(NtBu)Cl3]. Reduction of [MoCpClCl4] with two equivalents of Na/Hg gives the dinuclear molybdenum(III) complex [MoCpCl]2(μ-Cl)4. All of the reported compounds were characterized by elemental analysis and 1H- and 13C NMR-spectroscopy.The authors acknowledge DGICYT (project PB92-0178-C) for financial support

Synthesis of degradable cationic carbosilane dendrimers based on Si-O or ester bonds

Several cationic carbosilane dendrimers have been synthesized containing two different types of degradable bonds: SieO and ester bonds. The first type of systems was prepared by reacting carbosilane dendrimers containing peripheral SieCl bonds with first generation dendrons presenting a eOH function at the focal point and amine peripheral functions. The second type of systems was prepared by esterification between a dendrimer containing acid groups and an alcoholamine. The stability in water of both types of cationic systems was evaluatedMinisterio de Economía y Empres

Half-sandwich isocyanide, phosphine, methyl and phosphanido pentamethylcyclopentadienylniobium(V) complexes

[NbCp★Cl4] Cp★ = ν5-C5Me5) reacts with one molar equivalent of isocyanides and phosphines to give pseudo-octahedral adducts [NbCp★Cl4·L], (Full-size image (<1 K), 4) and the dinuclear complex [∗[NbCp★Cl4∗]2(μ-dmpe)], 5. Reactions of [NbCp★Cl4] with appropriate amounts of MgClMe yield the correspodning dimethyl [NbCp★Cl2Me2], 6, and tetramethyl [NbCp★Me4], 7 derivatives. Similarly, when [∗[NbCp★Cl3∗2(μ-O)] an and 3 are treated with the alkylating magnesium reagent, [∗[NbCp★Me3∗]2(μ-O)], 8, and [NbCp★Cl3Me(PMe2Ph)], 9, are obtained in high yields. A new phosphanido-niobium(V) complex [NbCp★Cl3(PPh2)] 10, is formed in the reaction of the starting tetrachloro complex with one equivalent of LiPPh2. All the complexes were characterized by IR and NMR spectroscopy, and most of them were studied by mass spectrometry

Sulfonate-terminated carbosilane dendron-coated nanotubes: a greener point of view in protein sample preparation

Reduction or removal of solvents and reagents in protein sample preparation is a requirement. Dendrimers can strongly interact with proteins and have great potential as a greener alternative to conventional methods used in protein sample preparation. This work proposes the use of single-walled carbon nanotubes (SWCNTs) functionalized with carbosilane dendrons with sulfonate groups for protein sample preparation and shows the successful application of the proposed methodology to extract proteins from a complex matrix. SEM images of nanotubes and mixtures of nanotubes and proteins were taken. Moreover, intrinsic fluorescence intensity of proteins was monitored to observe the most significant interactions at increasing dendron generations under neutral and basic pHs. Different conditions for the disruption of interactions between proteins and nanotubes after protein extraction and different concentrations of the disrupting reagent and the nanotube were also tried. Compatibility of extraction and disrupting conditions with the enzymatic digestion of proteins for obtaining bioactive peptides was also studied. Finally, sulfonate-terminated carbosilane dendron-coated SWCNTs enabled the extraction of proteins from a complex sample without using non-environmentally friendly solvents that were required so far

Strategies for penicillin V dendronization with cationic carbosilane dendrons and study of antibacterial properties.

Strategies to synthesize a cationic carbosilane dendron containing the antibiotic penicillin V potassium salt (PenVK) at the focal point are discussed. The preparation of such a compound requires the use of systems with no donor atoms such as N or S in their framework, because their presence favours the rupture of the penicillin beta-lactam ring. The antibacterial activity of the new dendron containing ammonium groups, at the periphery, and the PenV moiety, at the focal point, against gram-positive Staphylococcus aureus strains was evaluated. These results were compared with those obtained for free PenVK, a related cationic dendron without a penicillin moiety at the focal point, and also compared with an equimolar mixture of this last dendron with free PenV. The data obtained indicate that, on one hand, the conjugation or interaction of PenV with cationic dendrons reduces its activity in comparison with free PenVK. On the other hand, the penicillin dendron is able to release the antibiotic in the presence of esterease, due to the breaking of the ester bond in this derivative.Ministerio de Economía y Empres

Fluorescein labelled cationic carbosilane dendritic systems for biological studies

Cationic carbosilane dendrimers and dendrons labelled with one fluorescein unit have been synthesized. For dendrimers (generations 1–3), a random procedure was followed by successive addition of two types of thiol compounds to vinyl terminated derivatives, first one with –NH3Cl and second one with –NMe2HCl functions, subsequent reaction with FITC and finally quaternization with MeI. For dendrons, the use of compounds with a –NH2 group at the focal point and –NMe2 functions at the periphery allowed us to obtain the corresponding fluoresceinated cationic derivatives. The toxicity of these dendritic molecules was studied by MTT and their interaction with siRNA Nef by electrophoresis. Finally, second generation dendrimer and their dendriplexes with siRNA Nef were chosen as a model to analyse their in vivo biodistribution in a BALB/c mouse model. The highest levels for dendriplexes were found in spleen and liver, followed in lymph nodes, while lower levels were found in kidneys. This distribution is in accordance with long circulation times.Ministerio de Economía y EmpresaComunidad de MadridMinisterio de Educación y Cienci

Amphiphilic Cationic Carbosilane-PEG Dendrimers: Synthesis and Applications in Gene Therapy

Here we synthesized carbosilane, generation 1 to 3, and PEG-based dendrons functionalized at the periphery with NHBoc groups and at the focal point with azide and alkyne moieties, respectively. The coupling of these two types of dendrons via click chemistry led to the formation of new hybrid dendrimers with two distinct moieties, the hydrophobic carbosilane and the hydrophilic PEG-based dendron. The protected dendrimers were transformed into cationic ammonium dendrimers. These unique amphiphilic dendrimers were studied as vectors for gene therapy against HIV in peripheral blood mononuclear cells (PBMC) and their performance was compared with that of a PEG-free carbosilane dendrimer. The presence of the PEG moiety afforded lower toxicities and evidenced a weaker interaction between dendrimers and siRNA when compared to the homodendrimer analogous. Both features, lower toxicity and lower dendriplex strength, are key properties for use of these vectors as carriers of nucleic material.Comunidad de MadridMinisterio de Sanidad y ConsumoMinisterio de Economía y Empres

Exploring the Interactions of Ruthenium (II) carbosilane metallodendrimers and precursors with model cell membranes through a dual spin label spin probe technique using EPR

Dendrimers exhibit unique interactions with cell membranes, arising from their nanometric size and high surface area. To a great extent, these interactions define their biological activity and can be reported in situ by spin-labelling techniques. Schiff-base carbosilane ruthenium (II) metallodendrimers are promising antitumor agents with a mechanism of action yet to explore. In order to study their in situ interactions with model cell membranes occurring at a molecular level, namely cetyltrimethylammonium bromide micelles (CTAB) and lecithin liposomes (LEC), electron paramagnetic resonance (EPR) was selected. Both a spin probe, 4-(N,N-dimethyl-N-dodecyl)ammonium-2,2,6,6-tetramethylpiperidine-1-oxyl bromide (CAT12), able to enter the model membranes, and a spin label, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) covalently attached at newly synthesized heterofunctional dendrimers, were used to provide complementary information on the dendrimer-membrane interactions. The computer-aided EPR analysis demonstrated a good agreement between the results obtained for the spin probe and spin label experiments. Both points of view suggested the partial insertion of the dendrimer surface groups into the surfactant aggregates, mainly CTAB micelles, and the occurrence of both polar and hydrophobic interactions, while dendrimer-LEC interactions involved more polar interactions between surface groups. We found out that subtle changes in the dendrimer structure greatly modified their interacting abilities and, subsequently, their anticancer activity

Study of non-covalent interactions on dendriplex formation: Influence of hydrophobic, electrostatic and hydrogen bonds interactions

The interaction of a double stranded small interference RNA (siRNA Nef) with cationic carbosilane dendrimers of generations 1-3 with two different ammonium functions at the periphery ([-NMe2R](+), R=Me, (CH2)(2)OH) has been studied by experimental techniques (zeta potential, electrophoresis, single molecule pulling experiments) and molecular dynamic calculations. These studies state the presence of different forces on dendriplex formation, depending on generation and type of ammonium group. Whilst for higher dendrimers electrostatic forces mainly drive the stability of dendriplexes, first generation compounds can penetrate into siRNA strands due to the establishment of hydrophobic interactions. Finally, in the particular case of first generation dendrimer [G(1)O(3)(NMe2(CH2)(2)OH))(6)](6+); the presence of hydroxyl groups reinforces dendriplex stability by hydrogen bonds formation. However, since these small dendrimers do not cover the RNA, only higher generation derivatives protect RNA from degradation.University of Alcalá; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN); Instituto de Investigación Sanitaria Gregorio Marañón; Universitat de Barcelon

Structure-activity relationship study of cationic carbosilane dendritic systems as antibacterial agents

This work focuses on the antibacterial activity against Gram-positive Staphylococcus aureus and Gramnegative Escherichia coli and the hemolytic properties of two types of ammonium cationic carbosilane systems: dendrimers and dendrons. The effects of: i) the generation, ii) the type of peripheral groups near the cationic charges (a SiMe2 moiety or a S atom depending on the synthetic procedure, hydrosilylation or thiol-ene addition, respectively), iii) the core of dendrimers (polyphenoxo vs. Si atom) and iv) the focal point of dendrons (-N3, -NH2, -OH) have been assessed. The structure-activity relationship analysis indicates the importance of an adequate balance between the hydrophilic and lipophilic fragments of these molecules to reach the best antibacterial activity. Regarding hemolysis, lowest toxicity values were registered for dendritic systems with a sulfur atom close to the surface and, in the particular case of dendrons, for those with a hydroxyl focal point. One dendrimer and one dendron, both bearing a sulfur atom close to the surface, scored best in the activity-toxicity relationship analysis and were chosen for resistance assays. No changes in the inhibitory and bactericidal capacity in the case of the dendron and only a slight increase of these values for the dendrimer were observed after 15 subculture cycles. Furthermore, these two compounds stayed active towards different strains of resistant bacteria and avoid formation of biofilm at concentrations over the minimum inhibitory concentration (MIC).Ministerio de Economía y Empres