The Michael donor-acceptor reactivity of curcumins in the synthesis of diverse multi-functional scaffolds.

Curcumin is a key constituent of turmeric with a variety of biological activities. From a chemical point of view, curcumin contains different functional groups that can undergo multiple transformations such as Michael addition, cycloaddition, click reaction, polymerisation, etc. Among these, Michael-type reactions under benign conditions constitute a captivating domain of curcumin's reactivity. To the best of our knowledge, no review focusing on the Michael donor-acceptor reactivity of curcumins has been published to date. Herein, we have compiled the chemistry of curcumins with respect to their chemical synthesis, biosynthesis, and involvement in chemical transformations, especially in Michael additions with advances in mechanistic aspects and understanding.

Approaching Industrially Relevant Current Densities for Hydrogen Oxidation with a Bioinspired Molecular Catalytic Material.

Integration of efficient platinum-group-metal (PGM)-free catalysts to fuel cells and electrolyzers is a prerequisite to their large-scale deployment. Here, we describe the development of a molecular-based anode for the hydrogen oxidation reaction (HOR) through noncovalent integration of a DuBois type Ni bioinspired molecular catalyst at the surface of a carbon nanotube modified gas diffusion layer. This mild immobilization strategy enabled us to gain high control over the loading in catalytic sites. Additionally, through the adjustment of the hydration level of the active layer, a new record current density of 214 ± 20 mA cm-2 could be reached at 0.4 V vs RHE with the PGM-free anode, at 25 °C. Near industrially relevant current densities were obtained at 55 °C with 150 ± 20 and 395 ± 30 mA cm-2 at 0.1 and 0.4 V overpotentials, respectively. These results further demonstrate the relevance of such molecular approaches for the development of electrocatalytic platforms for energy conversion.

Catalytic Processes for the Neutralization of Sulfur Mustard.

Research on the decontamination of the chemical warfare agent sulfur mustard pursues several objectives that include the neutralization of spared ammunition, the cleaning of affected areas, and also the development of protective equipment or tools. Neutralization of vesicant sulfur mustard involves different chemical routes such as hydrolysis, dehydrochlorination, oxidation, or complete mineralization. This review weighs the pros and cons associated with the different systems reported in the literature, with an emphasis on catalytic procedures, to selectively convert sulfur mustard or its simulants into harmless products.

Recognition protein C1q of innate immunity agglutinates nanodiamonds without activating complement.

Nanodiamonds are promising nanomedicines for diagnostic and therapeutic applications. As nanodiamonds are mainly administered intravenously, it is critical to understand the humoral immune response upon exposure to nanodiamonds. Here, we report the interactions of pristine, oxidized, and PEG-functionalized nanodiamonds with human complement, an important part of our humoral innate immunity. In particular, we report the nanodiamond binding properties of the recognition protein of the classical complement pathway: C1q, which also takes part in many other physiological and pathological processes. Our results show similar trends in the effects of C1q on the three types of nanodiamonds. Complement activation assays using human serum show that the nanodiamonds trigger slight activities via the alternative pathway and no response via the classical pathway. Nevertheless, surface plasmon resonance shows that C1q binds the nanodiamonds and transmission electron microscopy reveals their agglutination. Studies with macrophages further show that C1q attachment affects their phagocytosis and cytokine response.

Controlled Release of a Micelle Payload via Sequential Enzymatic and Bioorthogonal Reactions in Living Systems.

A bioorthogonal approach is explored to release the content of nanoparticles on demand. Exploiting our recently described click-and-release technology, we developed a new generation of cleavable micelles able to disassemble through a sequential enzymatic and bioorthogonal activation process. Proof-of-concept experiments showed that this new approach could be successfully used to deliver the substances encapsulated into micelles in living cells as well as in mice by two complementary targeted strategies.

Combination of Aryl Diselenides/Hydrogen Peroxide and Carbon-Nanotube/Rhodium Nanohybrids for Naphthol Oxidation: An Efficient Route towards Trypanocidal Quinones.

This work reports a combination of aryl diselenides/hydrogen peroxide and carbon-nanotube (CNT)/rhodium nanohybrids (RhCNT) for naphthol oxidation towards the synthesis of 1,4-naphthoquinones and evaluation of their relevant trypanocidal activity. Under a combination of (PhSe)2 /H2 O2 in the presence of O2 in iPrOH/hexane, several benzenoid (A-ring)-substituted quinones were prepared in moderate to high yields. We also studied the contribution of RhCNT as co-catalyst in this process and, in some cases, yields were improved. This method provides an efficient and versatile alternative for preparing A-ring-modified naphthoquinonoid compounds with relevant biological profile.

Manipulating Simple Reactive Chemical Units: Fishing for Alkaloids from Complex Mixtures.

This Concept article describes how key C10 molecular scaffolds, too reactive to be obtained through classical multistep synthesis, were targeted in the most simple reaction conditions, reproducing those that may be encountered in living cells. The rationale was that small amounts of these reactive intermediates might be formed in situ from cheap and abundant reactants (i.e., glutaraldehyde and tetrahydropyridine) resulting, upon further rearrangement in "complex mixtures" from which natural substances would arise. From five types of mixtures, at least six full carbon skeletons of known natural substances were formed spontaneously. This work also led to the discovery of new plausible biosynthetic achiral precursors in the Nitraria metabolism.

Polymer-Decorated Carbon Nanotubes as Transducers for Label-Free Photonic Biosensors.

A biosensor taking advantage of the optical properties of sorted carbon nanotubes has been developed. A polyfluorene polymer bearing azido groups was synthesized and used for the selective extraction of semi-conducting nanotubes from the bulk population. The resulting polymer-decorated nanotubes were then conjugated by click-chemistry to a ligand unit (biotin), and the sensing properties of the biotinylated nanotubes were investigated by photoluminescence measurements, upon interaction with the streptavidin target.

Cooperative dehydrogenation of N-heterocycles using a carbon nanotube-rhodium nanohybrid.

Rhodium nanoparticles were anchored on carbon nanotubes and the resulting nanohybrid was studied as co-catalyst, along with tert-butylcatechol, for the dehydrogenation of various N-heterocycles. The co-catalytic system operates in high yields, under the mildest conditions reported so far, and can be applied to a wide variety of secondary amine-containing scaffolds.

On the characterization of the surface chemistry of quantum dots.

The interaction of ligands with the surface of quantum dots (QD) was studied using tritiated oleic acid as an ultrasensitive reporter. The use of labeled oleic acid not only permitted to quantify the number of ligands attached to the surface of QDs of various sizes but also enabled the investigation of the relative affinity of different ligand types for the nanocrystal's surface.

Aqueous Photocatalytic Oxidation of Thioethers with Polydiacetylene Micelle Nanoreactors.

A semi-heterogeneous photocatalytic system was assembled through encapsulation of a lipophilic porphyrin in stabilized polydiacetylene micelles. The colloidal nanohybrid catalyst was valorized in the aerobic photo-oxidation of sulfides to the corresponding sulfoxides. Micelles behaved as nanoreactors by creating a favorable environment for the photo-activation of oxygen nearby thioethers and subsequent sulfoxidation. The process operates selectively under visible light and air atmosphere, with low catalytic loading and in water as the only solvent.

Tumor-Targeted Perfluorinated Micelles as Efficient Theranostic Agents Combining Positron Emission Tomography and Radiosensitization.

We report the synthesis of biocompatible perfluorinated micelles designed to improve radiotherapeutic efficacy in a radioresistant tumor environment. In vitro and in vivo behaviors of perfluorinated micelles were assessed at both cellular and tissular levels. The micellar platform offers key advantages as theranostic tool: (i) small size, allowing deep tissue penetration; (ii) oxygen transport to hypoxic tissues; (iii) negligible toxicity in the absence of ionizing radiation; (iv) internalization into cancer cells; (v) potent radiosensitizing effect; and (vi) excellent tumor-targeting properties, as monitored by positron emission tomography. We have demonstrated strong in vitro radiosensitizing effects of the micelle and in vivo tumor targeting, making this nanometric carrier a promising tool for the potentiation of focused radiotherapy.

Phototriggered Cytotoxicity of Ferrocene-Based Micelles - A Nonconventional Approach to Phototherapy.

We report the design, synthesis, and in vitro evaluation of stimuli-responsive nanoscale micelles that can be activated by light to induce a cytotoxic effect. Micelles were assembled from amphiphilic units made of a photoactivatable ferrocenyl linker, connected on one side to a lipophilic chain, and on the other side to a hydrophilic pegylated chain. In vitro experiments indicated that pristine micelles ("off" state) were nontoxic to MCF-7 cancer cells, even at high concentrations, but became potent upon photoactivation ("on" state). The illumination process led to the dissociation of the micelles and the concomitant release of iron species, triggering cytotoxicity.

Spontaneous formation of nitrarine and polycyclic skeletons related to Nitraria indolic alkaloids under non-enzymic conditions.

Mixtures of tryptamine and reactive C5 units, presumably derived from lysine in nature, were studied to ascertain the spontaneous formation of the complex polycyclic alkaloid nitrarine. Several indolic compounds tracing the unified metabolism within the Nitraria genus were also characterized.

"Clickable" hydrosoluble PEGylated cryptophane as a universal platform for 129Xe magnetic resonance imaging biosensors.

We describe the synthesis of a highly water-soluble cryptophane 1 that can be seen as a universal platform for the construction of (129)Xe magnetic resonance imaging (MRI)-based biosensors. Compound 1 is easily functionalized by Huisgen cycloaddition and exhibits excellent xenon-encapsulation properties. In addition, 1 is nontoxic at the concentrations typically used for hyperpolarized (129)Xe MRI.

Semisynthesis of macrocarpal C and analogues by selective dehydration of macrocarpal A or B.

Macrocarpals A and C are structurally related compounds that have been extracted from different Eucalyptus species. Although macrocarpal C is of biological interest, its isolation in pure form is difficult to achieve. We report herein an efficient method for the semisynthesis of macrocarpal C by selective exo-dehydration of another member of the macrocarpal family, macrocarpal A. We also report the semisynthesis of three new macrocarpal structures derived from either macrocarpal A or B.

Continuous Flow Photocatalytic Hydrogen Production from Water Synergistically Activated by TiO2, Gold Nanoparticles, and Carbon Nanotubes.

Titanium dioxide nanoparticles were combined with carbon nanotubes and gold to develop improved photocatalysts for the production of hydrogen from water. The entangled nature of the nanotubes allowed for the integration of the photoactive hybrid catalyst, as a packed-bed, in a microfluidic photoreactor, and the chips were studied in the photocatalyzed continuous flow production of hydrogen. The combination of titanium dioxide with carbon nanotubes and gold significantly improved hydrogen production due to a synergistic effect between the multi-component system and the stabilization of the active catalytic species. The titanium dioxide/carbon nanotubes/gold system permitted a 2.5-fold increase in hydrogen production, compared to that of titanium dioxide/carbon nanotubes, and a 20-fold increase, compared to that of titanium dioxide.

Sonoporation-assisted micelle delivery in subcutaneous glioma-bearing mice evaluated by PET/fluorescent bi-modal imaging.

Tumor-specific drug delivery is a major challenge for the pharmaceutical industry. Nanocarrier systems have been widely investigated to increase and control drug delivery to the heterogeneous tumor microenvironment. Classically, the uptake of nanocarriers by solid tumor tissues is mainly mediated by the enhanced permeability and retention effect (EPR). This EPR effect depends on the tumor type, its location, the physicochemical properties of the carriers, and the blood perfusion of the tumoral lesions. The main goal of this study was to evaluate in vivo tumor uptake of micelle carriers, assisted by microbubble/ultrasound sonoporation. Micelles were tracked using bi-modal imaging techniques to precisely localize both the nanocarrier and its payload. Micelles were loaded with a near infrared fluorophore and radiolabeled with zirconium-89. Their pharmacokinetics, biodistribution and passive tumor targeting properties were evaluated in a subcutaneous glioblastoma (U-87 MG) mouse model using optical and PET imaging. Finally, accumulation and diffusion into the tumor micro-environment was investigated under microbubble-assisted sonoporation, which helped homogenize the delivery of the micelles. The in vivo experiments showed a good correlation between optical and PET images and demonstrated the stability of the micelles in biological media, their high and long-term retention in the tumors and their clearance through the hepato-biliary pathway. This study demonstrates that bi-modal imaging techniques are powerful tools for the development of new nanocarriers and that sonoporation is a promising method to homogenize nanomedicine delivery to tumors.

Targeted delivery of LXR-agonists to atherosclerotic lesions mediated by polydiacetylene micelles.

We report the development of compact and stabilized micelles incorporating a synthetic LXR agonist prodrug for the passive targeting of atherosclerotic lesions and therapeutic intervention. In vivo studies showed that the nanohybrid micelles exhibited favorable pharmacokinetics/biodistribution and were able to upregulate, to some extent, LXR target genes with no alteration of lipid metabolism.

Solvent-free hydroboration of alkenes and alkynes catalyzed by rhodium-ruthenium nanoparticles on carbon nanotubes.

A heterogeneous catalyst consisting of bimetallic rhodium-ruthenium particles immobilized on carbon nanotubes was used in the hydroboration reaction and proved highly effective for a variety of alkenes and alkynes. The reactions were carried out with low catalytic loadings (0.04 mol%), under solvent-free conditions, and at room temperature. In addition, to demonstrate its recyclability, the catalyst was recovered by a simple centrifugation process and reused over 5 consecutive cycles without losing any activity.