Functionalization of Siloxanes with Arynes Generated from o-Triazenylarylboronic Acids.

Herein, we report the functionalization of polyhedral oligosilsesquioxanes (POSS) and related siloxanes with arynes. Using o-triazenylarylboronic acids as aryne precursors and silica gel as the activator, the transformation of siloxane bearing various arynophilic moieties on the side chains was achieved with high yields without touching the siloxane core. This method was applied to the conjugation of POSS and pharmaceutical cores using an aryne derived from the synthetic intermediate of cabozantinib. Furthermore, orthogonal dual functionalization of POSS was realized by combining the aryne reaction with Huisgen cyclization.

SilE-R and SilE-S-DABB Proteins Catalying Enantiospecific Hydrolysis of Organosilyl Ethers.

Silyl ethers fulfil a fundamental role in synthetic organic chemistry as protecting groups and their selective cleavage is an important factor in their application. We present here for the first time two enzymes, SilE-R and SilE-S, which are able to hydrolyse silyl ethers. They belong to the stress-response dimeric A/B barrel domain (DABB) family and are able to cleave the Si-O bond with opposite enantiopreference. Silyl ethers containing aromatic, cyclic or aliphatic alcohols and, depending on the alcohol moiety, silyl functions as large as TBDMS are accepted. The X-ray crystal structure of SilE-R, determined to a resolution of 1.98 Å, in combination with mutational studies, revealed an active site featuring two histidine residues, H8 and H79, which likely act synergistically as nucleophile and Brønsted base in the hydrolytic mechanism, which has not previously been described for enzymes. Although the natural function of SilE-R and SilE-S is unknown, we propose that these 'silyl etherases' may have significant potential for synthetic applications.

Janus bifunctional periodic mesoporous organosilica.

Synthesis of a Janus periodic mesoporous organosilica material (JPMO) is presented here. In this strategy, the surface of the hollow silica material was selectively functionalized with two different bridged organic-inorganic hybrid groups. It was found that the resulting bifunctional material is able to form a stable Pickering emulsion. This new type of PMO material may be suitable for widespread applications in various fields related to material science and catalysis.

Use of Polyhedral Oligomeric Silsesquioxane (POSS) in Drug Delivery, Photodynamic Therapy and Bioimaging.

Polyhedral oligomeric silsesquioxanes (POSS) have attracted considerable attention in the design of novel organic-inorganic hybrid materials with high performance capabilities. Features such as their well-defined nanoscale structure, chemical tunability, and biocompatibility make POSS an ideal building block to fabricate hybrid materials for biomedical applications. This review highlights recent advances in the application of POSS-based hybrid materials, with particular emphasis on drug delivery, photodynamic therapy and bioimaging. The design and synthesis of POSS-based materials is described, along with the current methods for controlling their chemical functionalization for biomedical applications. We summarize the advantages of using POSS for several drug delivery applications. We also describe the current progress on using POSS-based materials to improve photodynamic therapies. The use of POSS for delivery of contrast agents or as a passivating agent for nanoprobes is also summarized. We envision that POSS-based hybrid materials have great potential for a variety of biomedical applications including drug delivery, photodynamic therapy and bioimaging.

Super-Assembled Periodic Mesoporous Organosilica Frameworks for Real-Time Hypoxia-Triggered Drug Release and Monitoring.

Hypoxia, induced by inadequate oxygen supply, is a key indication of various major illnesses, which necessitates the need to develop new nanoprobes capable of sensing hypoxia environments for the targeted system monitoring and drug delivery. Herein, we report a hypoxia-responsive, periodic mesoporous organosilica (PMO) nanocarrier for repairing hypoxia damage. ß-cyclodextrin (ß-CD) capped azobenzene functionalization on the PMO surface could be effectively cleaved by azoreductase under a hypoxia environment. Moreover, the nanosystem is equipped with fluorescence resonance energy transfer (FRET) pair (tetrastyrene derivative (TPE) covalently attached to the PMO framework as the donor and Rhodamine B (RhB) in the mesopores as the receptor) for intracellular visualization and tracking of drug release in real-time. The design of intelligent nanocarriers capable of simultaneous reporting and treating of hypoxia conditions highlights a great potential in the biomedical domain.

A POSS-assisted fluorescent probe for the rapid detection of HClO in mitochondria with a large emission wavelength in dual channels.

Hypochlorous acid (HClO) is closely related to many diseases and is an inevitable part of the physiological processes. It is significant to detect HClO in mitochondria for getting meaningful physiological and pathological information. However, adequate tools to detect HClO with emissions in two channels are rarely reported. To achieve this target, in this work, a "turn-off" visual and near infrared (NIR) fluorescent dual emission probe D6 based on polyhedral oligomeric silsesquioxanes (POSS) was successfully designed and synthesized. D6 showed high selectivity and sensitivity to HClO. Notably, the emission wavelength of D6 reached 820 nm due to the assistance of the POSS cage. In addition, bioimaging experiments clearly showed that probe D6 promoted the visualization of exogenous and endogenous HClO in living HepG2 cells and zebrafish models.

Synthesis of dendritic mesoporous organosilica nanoparticles under a mild acidic condition with homogeneous wall structure and near-neutral surface.

Dendritic mesoporous organosilica nanoparticles were synthesized under a mild acidic condition (pH 6.2), featuring a molecularly homogeneous wall structure and an unusual near-neutral charged surface, consequently enabling reduced protein fouling property.

The development of an Amber-compatible organosilane force field for drug-like small molecules.

As members of the group IVA elements, silicon and carbon have long been thought of as isosteres of each other in drug design. However, the lack of silicon parameters in current main stream force fields hinders the computational study of this important element in drug discovery. Thus, in this study, we attempted to supplement the parameters of organosilanes in the General Amber Force Field (GAFF2). The parameters have been designed following the principles of GAFF2 to make it compatible with the Amber force field family. The accuracy of the parameters was discussed by comparing the pair interaction energy, the liquid properties, and the structures and alchemical binding free energy differences for a set of protein-ligand complexes.

Biodegradable and Biocompatible Silatrane Polymers.

In this study, new biodegradable and biocompatible amphiphilic polymers were obtained by modifying the peripheral hydroxyl groups of branched polyethers and polyesters with organosilicon substituents. The structures of the synthesized polymers were confirmed by NMR and GPC. Organosilicon moieties of the polymers were formed by silatranes and trimethylsilyl blocks and displayed hydrophilic and hydrophobic properties, respectively. The effect of the ratio of hydrophilic to hydrophobic organosilicon structures on the surface activity and biological activity of macromolecules was studied, together with the effect on these activities of the macromolecules' molecular weight and chemical structure. In particular, the critical micelle concentrations were determined, the effect of the structure of the polymers on their wetting with aqueous solutions on glass and parafilm was described, and the aggregation stability of emulsions was studied. Finally, the effect of the polymer structures on their antifungal activity and seed germination stimulation was examined.

Designer Anticancer Nanoprodrugs with Self-Toxification Activity Realized by Acid-triggered Biodegradation and In†Situ Fragment Complexation.

Prodrugs that allow in situ chemical conversion of less toxic precursors into active drugs in response to certain stimuli are promising anticancer candidates. Herein, we present a novel design of nanoprodrugs with a "degradation-mediated self-toxification" strategy, which realizes intracellular synthesis of anticancer agents using the nanoparticles' own degradation fragments as the precursors. To fulfill this concept, a metal complexing dicyclohexylphosphine (DCP) organosilane is carefully screened out from various ligands to conjugate onto Pd(OH)2 nanodots confined hollow silica nanospheres (PD-HSN). This constructed nanoprodrug shows acid-triggered degradation in lysosomes and neutralizes protons to induce lysosomes rupturing, generating predesigned less toxic fragments (Pd2+ and DCP-silicates) that complex into DCP/Pd complex in situ for inducing DNA damage, leading to enhanced anticancer activity against various cancer cell lines as well as in a xenograft tumour model.

Synthesis of Silsesquioxanes with Substituted Triazole Ring Functionalities and Their Coordination Ability.

A synthesis of a series of mono-T8 and difunctionalized double-decker silsesquioxanes bearing substituted triazole ring(s) has been reported within this work. The catalytic protocol for their formation is based on the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) process. Diverse alkynes were in the scope of our interest-i.e., aryl, hetaryl, alkyl, silyl, or germyl-and the latter was shown to be the first example of terminal germane alkyne which is reactive in the applied process' conditions. From the pallet of 15 compounds, three of them with pyridine-triazole and thiophenyl-triazole moiety attached to T8 or DDSQ core were verified in terms of their coordinating properties towards selected transition metals, i.e., Pd(II), Pt(II), and Rh(I). The studies resulted in the formation of four SQs based coordination compounds that were obtained in high yields up to 93% and their thorough spectroscopic characterization is presented. To our knowledge, this is the first example of the DDSQ-based molecular complex possessing bidentate pyridine-triazole ligand binding two Pd(II) ions.

Recent Advances in Polyurethane/POSS Hybrids for Biomedical Applications.

Advanced organic-inorganic materials-composites, nanocomposites, and hybrids with various compositions offer unique properties required for biomedical applications. One of the most promising inorganic (nano)additives are polyhedral oligomeric silsesquioxanes (POSS); their biocompatibility, non-toxicity, and phase separation ability that modifies the material porosity are fundamental properties required in modern biomedical applications. When incorporated, chemically or physically, into polyurethane matrices, they substantially change polymer properties, including mechanical properties, surface characteristics, and bioactivity. Hence, this review is dedicated to POSS-PU composites that have recently been developed for applications in the biomedical field. First, different modes of POSS incorporation into PU structure have been presented, then recent developments of PU/POSS hybrids as bio-active composites for scaffolds, cardiovascular stents, valves, and membranes, as well as in bio-imaging and cancer treatment, have been described. Finally, characterization and methods of modification routes of polyurethane-based materials with silsesquioxanes were presented.

Anticalcification Potential of POSS-PEG Hybrid Hydrogel as a Scaffold Material for the Development of Synthetic Heart Valve Leaflets.

Calcification of bioprosthetics is a primary challenge in the field of artificial heart valves and a main reason for biological heart valve prostheses failure. Recent advances in nanomaterial science have promoted the development of polymers with advantageous properties that are likely suitable for artificial heart valves. In this work, we developed a nanocomposite polymeric biomaterial POSS-PEG (polyhedral oligomeric silsesquioxane-polyethylene glycol) hybrid hydrogel, which not only has improved mechanical and surface properties but also excellent biocompatibility. The results of atomic force microscopy and in vivo animal experiments indicated that the content of POSS in the PEG matrix plays an important role on the surface and contributes to its biological properties, compared to the decellularized porcine aortic valve scaffold. Additionally, this modification leads to enhanced protection of the hydrogel from thrombosis. Furthermore, the introduction of POSS nanoparticles also gives the hydrogel a better calcification resistance efficacy, which was confirmed through in vitro tests and animal experiments. These findings indicate that POSS-PEG hybrid hydrogel is a potential material for functional heart valve prosthetics, and the use of POSS nanocomposites in artificial valves may offer potential long-term performance and durability advantages.

Generation of Bis(ferrocenyl)silylenes from Siliranes.

Divalent silicon species, the so-called silylenes, represent attractive organosilicon building blocks. Isolable stable silylenes remain scarce, and in most hitherto reported examples, the silicon center is stabilized by electron-donating substituents (e.g., heteroatoms such as nitrogen), which results in electronic perturbation. In order to avoid such electronic perturbation, we have been interested in the chemistry of reactive silylenes with carbon-based substituents such as ferrocenyl groups. Due to the presence of a divalent silicon center and the redox-active transition metal iron, ferrocenylsilylenes can be expected to exhibit interesting redox behavior. Herein, we report the design and synthesis of a bis(ferrocenyl)silirane as a precursor for a bis(ferrocenyl)silylene, which could potentially be used as a building block for redox-active organosilicon compounds. It was found that the isolated bis(ferrocenyl)siliranes could be a bottleable precursor for the bis(ferrocenyl)silylene under mild conditions.

Hybrid Porous Microparticles Based on a Single Organosilica Cyclophosphazene Precursor.

Porous organosilica microparticles consisting of silane-derived cyclophosphazene bridges were synthesized by a surfactant-mediated sol-gel process. Starting from the substitution of hexachlorocyclotriphosphazene with allylamine, two different precursors were obtained by anchoring three or six alkoxysilane units, via a thiol-ene photoaddition reaction. In both cases, spherical, microparticles (size average of ca. 1000 nm) with large pores were obtained, confirmed by both, scanning and transmission electron microscopy. Particles synthesized using the partially functionalized precursor containing free vinyl groups were further functionalized with a thiol-containing molecule. While most other reported mesoporous organosilica particles are essentially hybrids with tetraethyl orthosilicate (TEOS), a unique feature of these particles is that structural control is achieved by exclusively using organosilane precursors. This allows an increase in the proportion of the co-components and could springboard these novel phosphorus-containing organosilica microparticles for different areas of technology.

Evaluation of Polyhedral Oligomeric Silsesquioxane Porphyrin Derivatives on Photodynamic Therapy.

Polyhedral oligomeric silsesquioxane (POSS) is a promising scaffold to be used as delivery system. POSS can modify the properties of photosensitizers to enhance their efficacy toward photodynamic therapy (PDT). In this work, we designed, synthesized and characterized five different POSS porphyrin (POSSPs 1-5) derivatives containing hydrophobic (1-3) and hydrophilic (4 and 5) functional groups. In general, all the POSSPs showed a better singlet oxygen quantum yield than the parent porphyrins due to the steric hindrance from the POSS unique structure. POSSPs 1 and 3 containing isobutyl groups showed better PDT performance in cancer cells at lower concentrations than POSSPs 4 and 5. However; at higher concentrations, the POSSP4 containing hydrophilic groups has an enhanced PDT efficiency as compared with the parent porphyrin. We envision that the chemical tunability of POSSs can be used as a promising option to improve the delivery and performance of photosensitizers.

Tert-butyldimethylsilyl chitosan synthesis and characterization by analytical ultracentrifugation, for archaeological wood conservation.

The Oseberg ship is one of the most important archaeological testimonies of the Vikings. After excavation in 1904, the wooden gravegoods were conserved using alum salts. This resulted in extreme degradation of a number of the objects a hundred years later through acid depolymerisation of cellulose and lignin. The fragile condition of the artefacts requires a reconsolidation which has to be done avoiding water as solvent. We synthesized tert-butyldimethylsilyl (TBDMS) chitosan which is soluble in a 50:50 solution of ethyl acetate and toluene. Measurement of its molecular weight, to anticipate its penetration, provided a challenge as the density difference of the polymer and solvent was too small to provide adequate solute redistribution under a centrifugal field, so a two-stage process was implemented (i) determination of the weight-average molar mass of the aqueous soluble activated precursor, chitosan mesylate, Mw,mc using sedimentation equilibrium with the SEDFIT-MSTAR algorithm, and determination of the degree of polymerisation DP; (ii) measurement of the average degree of substitution DSTBDMS of the TBDMS group on each chitosan monosaccharide monomer unit using NMR, to augment the Mw,mc value to give the molar mass of the TBDMS-chitosan. For the preparation, we find Mw = 9.8 kg·mol-1, which is within the acceptable limit for penetration and consolidation of degraded wood. Future work will test this on archaeological wood from different sources.

Design, Preparation and Thermal Characterization of Polystyrene Composites Reinforced with Novel Three-Cages POSS Molecules.

Novel polystyrene (PS)/polyhedral oligomeric silsequioxanes (POSSs) nanocomposites were designed and prepared by in situ polymerization, using, for the first time, three-cage POSS molecules. The synthesized compounds were first characterized by Fourier transform infrared spectroscopy (FTIR) and 1H NMR spectroscopy to verify the obtaining of the designed products before their thermal performance was evaluated and compared with those of pristine PS and the corresponding single-cage POSSs nanocomposites. The thermal behaviour was checked by the means of the differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Scanning electron microscopy (SEM) was also used to confirm the hypothesis about the dispersion/aggregation of the POSS molecules into the polymer matrix. The parameters chosen to evaluate the thermal stability of the investigated compounds, namely temperature at 5% of mass loss (T5%) and solid residue at 700 °C, showed a significant increase in the stability of the polymers reinforced with the three-cages POSS, in comparison to both PS and single-cage POSS reinforced PSs, which therefore turn out to be promising molecular fillers for nanocomposite production.

Mechanism of the Iridium-Catalyzed Silylation of Aromatic C-H Bonds.

Phenanthroline ligands and [Ir(cod)(OMe)]2 form complexes that catalyze the silylation of aromatic and aliphatic C-H bonds. However, no experimental data on the identity of complexes related to the mechanism of this process or the mechanisms by which they react to functionalize C-H bonds have been reported. Herein, we describe our studies on the mechanism of the iridium-catalyzed silylation of aryl C-H bonds. The resting state of the catalyst is an iridium disilyl hydride complex (phenanthroline)Ir(SiMe(OTMS)2)2(H)(L), in which L varies with the arene and additives. An iridium disilyl hydride complex was isolated, characterized, and allowed to react with arenes to form aryl silanes. The kinetics of the reactions of electron-rich and electron-poor arenes showed that the rate-limiting step varies with the electronic properties of the arene. Computational studies on related iridium silyl complexes revealed that the high activity of iridium complexes containing sterically encumbered phenanthroline ligands is due to a change in the number of silyl groups bound to iridium between the resting state of the catalyst containing the hindered phenanthroline and that containing less-hindered phenanthroline.

The mannose 6-phosphate receptor targeted with porphyrin-based periodic mesoporous organosilica nanoparticles for rhabdomyosarcoma theranostics.

Porphyrin-based periodic mesoporous organosilica nanoparticles (PMO) synthesized from a large functional octatriethoxysilylated porphyrin precursor and allowing two-photon excitation photodynamic therapy (TPE-PDT) and NIR imaging were synthesized. These PMO were grafted with polyethylene glycol (PEG) moieties and an analogue of mannose 6-phosphate functionalized at the anomeric position (AMFA). AMFAs are known to efficiently target mannose 6-phosphate receptors (M6PRs) which are over-expressed in various cancers. Here, we demonstrated for the first time that M6PRs were over-expressed in rhabdomyosarcoma (RMS) cells and could be efficiently targeted with PMO-AMFA allowing TPE imaging and TPE-PDT of RMS cells. The comparison with healthy myoblasts demonstrated an absence of biological effects, suggesting a cancer cell specificity in the biomedical action observed.