Direct Synthesis of 3-Aryl Substituted Isocoumarins and Phthalides through Palladium Acetate Catalyzed C(sp2 )-H Activation in Ionic Liquids.

A novel Pd-catalysed oxidative coupling between benzoic acids and vinylarenes or acrylates to furnish isocoumarins and phthalides is reported. The reaction proceeds smoothly in molten tetrabutylammonium acetate via a selective C-H bond activation, with very low percentage of ligand-free palladium acetate as the catalyst, under atmospheric pressure of oxygen. Sub-stoichiometric amount of copper acetate is also required as a reoxidant for the palladium.

Synthesis and Investigation of Novel CHCA-Derived Matrices for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Analysis of Lipids.

A significant area of study and upgrading for increasing sensitivity and general performances of matrix-assisted laser-desorption ionization (MALDI) mass spectrometry (MS) is related to matrix design. Several efforts have been made to address the challenge of low-mass-region interference-free for metabolomics analysis and specifically for lipidomics. To this aim, rationally designed matrices as 4-chloro-α-cyanocinnamic acid (ClCCA) were introduced and reported to provide enhanced analytical performances. We have taken this rational design one step further by developing and optimizing new MALDI matrices with a range of modifications on the CHCA core, involving different functionalities and substituents. Of particular interest was the understanding of the electron-withdrawing (e.g., nitro-) or donating (e.g., methoxy-) effects along with the extent of conjugation on the ionization efficiency. In the present work, ten matrices were designed on a reasonable basis, synthesized, and characterized by NMR and UV spectroscopies and laser desorption ionization. With the assistance of these putative MALDI matrices, samples containing phospholipids (PL), and neutral di-/tri-acylglycerols (DAG, TAG) were investigated using milk, fish, blood, and human plasma extracts. In comparison with CHCA and ClCCA, four of them, viz. [(2E,4E)-2-cyano-5-(4-methoxyphenyl)penta-2,4-dienoic acid] (1), [(2E,4E)-2-cyano-5-(4-nitrophenyl)penta-2,4-dienoic acid] (2), [(E)-2-cyano-3-(6-methoxynaphthalen-2-yl)acrylic acid] (6) and [(E)-2-cyano-3-(naphthalen-2-yl)acrylic acid] (7) displayed good to even excellent performances as MALDI matrices in terms of ionization capability, interference-free spectra, S/N ratio, and reproducibility. Especially compound 7 (cyano naphthyl acrylic acid, CNAA) was the election matrix for PL analysis and matrix 2 (cyano nitrophenyl dienoic acid, CNDA) for neutral lipids such as DAG and TAG in positive ion mode.

Synthesis of Tailored Perfluoro Unsaturated Monomers for Potential Applications in Proton Exchange Membrane Preparation.

The aim of the present work is the synthesis and characterization of new perfluorinated monomers bearing, similarly to Nafion®, acidic groups for proton transport for potential and future applications in proton exchange membrane (PEM) fuel cells. To this end, we focused our attention on the synthesis of various molecules with (i) sufficient volatility to be used in vacuum polymerization techniques (e.g., PECVD)), (ii) sulfonic, phosphonic, or carboxylic acid functionalities for proton transport capacity of the resulting membrane, (iii) both aliphatic and aromatic perfluorinated tags to diversify the membrane polarity with respect to Nafion®, and (iv) a double bond to facilitate the polymerization under vacuum giving a preferential way for the chain growth of the polymer. A retrosynthetic approach persuaded us to attempt three main synthetic strategies: (a) organometallic Heck-type cross-coupling, (b) nucleophilic displacement, and (c) Wittig-Horner reaction (carbanion approach). Preliminary results on the plasma deposition of a polymeric film are also presented. The variation of plasma conditions allowed us to point out that the film prepared in the mildest settings (20 W) shows the maximum monomer retention in its structure. In this condition, plasma polymerization likely occurs mainly by rupture of the π bond in the monomer molecule.

Synthesis and Matrix Properties of α-Cyano-5-phenyl-2,4-pentadienic Acid (CPPA) for Intact Proteins Analysis by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry.

The effectiveness of a synthesized matrix, α-cyano-5-phenyl-2,4-pentadienic acid (CPPA), for protein analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in complex samples such as foodstuff and bacterial extracts, is demonstrated. Ultraviolet (UV) absorption along with laser desorption/ionization mass spectrometry (LDI-MS) experiments were systematically conducted in positive ion mode under standard Nd:YLF laser excitation with the aim of characterizing the matrix in terms of wavelength absorption and proton affinity. Besides, the results for standard proteins revealed that CPPA significantly enhanced the protein signals, reduced the spot-to-spot variability and increased the spot homogeneity. The CPPA matrix was successful employed to investigate intact microorganisms, milk and seed extracts for protein profiling. Compared to conventional matrices such as sinapinic acid (SA), α-cyano-4-hydroxycinnamic acid (CHCA) and 4-chloro-α-cyanocinnamic acid (CClCA), CPPA exhibited better signal-to-noise (S/N) ratios and a uniform response for most examined proteins occurring in milk, hazelnut and in intact bacterial cells of E. coli. These findings not only provide a reactive proton transfer MALDI matrix with excellent reproducibility and sensitivity, but also contribute to extending the battery of useful matrices for intact protein analysis.

Encapsulation of Curcumin-Loaded Liposomes for Colonic Drug Delivery in a pH-Responsive Polymer Cluster Using a pH-Driven and Organic Solvent-Free Process.

The present study aimed to develop and optimize liposome formulation for the colonic delivery of biologically active compounds. A strategy to facilitate such targeting is to formulate liposomes with a polymer coating sensitive to the pH shifts in the gastrointestinal tract. To this end, liposomes encapsulating curcumin-chosen as the biologically active compound model-and coated with the pH-responsive polymer Eudragit S100 were prepared and characterized. Curcumin was encapsulated into small unilamellar vesicles (SUVs) by the micelle-to-vesicle transition method (MVT) in a simple and organic solvent-free way. Curcumin-loaded liposomes were coated with Eudragit S100 by a fast and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and curcumin antioxidant activity. In particular, curcumin-loaded liposomes displayed size lower than 100 nm, encapsulation efficiency of 98%, high stability at both 4 °C and 25 °C, high in vitro antioxidant activity, and a cumulative release that was completed within 200 min. A good Eudragit S100 coating which did not alter the properties of the curcumin-loaded liposomes was obtained. The present work therefore provides a fast and solvent-free method to prepare pH-responsive polymer-coated liposomes for the colonic delivery of biologically active compounds.

Solvent-gated thin-film-transistors.

Electrical double layer (EDL) thin film transistors (TFTs) are an interesting class of transistors that use an electrolyte as the gating medium. Recently it has been demonstrated that pure organic solvents can also be used as gating media for TFTs without the addition of exogenous electrolytes. Here we present a systematic study of the performances of TFTs based on two different semiconductors (P3HT and ZnO) gated through nine different solvents either pure or loaded with NaCl. The nature of the solvent impacts the transfer characteristics of the TFT through a change in the gating capacitance while the threshold voltage remains unaffected. Depending on the polarity of solvents, addition of NaCl gives rise to different responses. TFTs gated through highly polar solvents are unaffected by the salt concentration while for low polarity solvents the output current increases with salt up to a plateau. Furthermore, when the semiconductor surface is covered with a high capacitance thin dielectric layer, the TFT output current becomes dependent on the NaCl concentration also for high polarity solvents. This phenomenology was rationalized considering the different contributions of Helmholtz and Guy-Chapman EDLs to the capacitance and the dielectric saturation that decreases the solvent dielectric constant within the Helmholtz EDL.

Heterogenization of Ketone Catalyst for Epoxidation by Low Pressure Plasma Fluorination of Silica Gel Supports.

Low pressure plasma was used for preparing heterogeneous organocatalysts 2-(A)-(C) suitable for dioxirane-mediated epoxidations. Heterogenization was accomplished by adsorption of the methyl perfluoroheptyl ketone (2) on fluorinated supports (A)-(C) deriving from the treatment of commercial C8-silica gel in low pressure plasma fed with fluorocarbons. Catalyst 2-(C) proved to be the most efficient one, promoting epoxidation of an array of alkenes, including unsaturated fatty esters like methyl oleate (10) and the triglyceride soybean oil (11), with the cheap potassium peroxymonosulfate KHSO5 (caroate) as a green oxidant. Notably, the perfluorinated matrix gives rise to the activation of caroate, generating singlet oxygen. Materials were characterized by infrared Attenuated Total Reflectance spectroscopy (ATR-FTIR), X-ray Photoelectron Spectroscopy (XPS ) and Emission Scanning Electron Microscope (FESEM).

One-Pot Conversion of Epoxidized Soybean Oil (ESO) into Soy-Based Polyurethanes by MoCl2O2 Catalysis.

An innovative and eco-friendly one-pot synthesis of bio-based polyurethanes is proposed via the epoxy-ring opening of epoxidized soybean oil (ESO) with methanol, followed by the reaction of methoxy bio-polyols intermediates with 2,6-tolyl-diisocyanate (TDI). Both synthetic steps, methanolysis and polyurethane linkage formation, are promoted by a unique catalyst, molybdenum(VI) dichloride dioxide (MoCl2O2), which makes this procedure an efficient, cost-effective, and environmentally safer method amenable to industrial scale-up.

Highly selective palladium-benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions.

The Pd-benzothiazol-2-ylidene complex I was found to be a chemoselective catalyst for the Tsuji-Trost allylation of active methylene compounds carried out under neutral conditions and using carbonates as allylating agents. The proposed protocol consists in a simplified procedure adopting an in situ prepared catalyst from Pd2dba3 and 3-methylbenzothiazolium salt V as precursors. A comparison of the performance of benzothiazole carbene with phosphanes and an analogous imidazolium carbene ligand is also proposed.

Palladium-catalyzed cross-coupling of styrenes with aryl methyl ketones in ionic liquids: direct access to cyclopropanes.

The combined use of Pd(OAc)2 , Cu(OAc)2 , and dioxygen in molten tetrabutylammonium acetate (TBAA) promotes an unusual cyclopropanation reaction between aryl methyl ketones and styrenes. The process is a dehydrogenative cyclizing coupling that involves a twofold CH activation at the α-position of the ketone. The substrate scope highlights the flexibility of the catalyst; a reaction mechanism is also proposed.

Eco-Friendly Catalytic Synthesis of Top Value Chemicals from Valorization of Cellulose Waste.

The total amount of cellulose from paper, wood, food, and other human activity waste produced in the EU is in the order of 900 million tons per year. This resource represents a sizable opportunity to produce renewable chemicals and energy. This paper reports, unprecedently in the literature, the usage of four different urban wastes such as cigarette butts, sanitary pant diapers, newspapers, and soybean peels as cellulose fonts to produce valuable industrial intermediates such as levulinic acid (LA), 5-acetoxymethyl-2-furaldehyde (AMF), 5-(hydroxymethyl)furfural (HMF), and furfural. The process is accomplished by the hydrothermal treatment of cellulosic waste using both Brønsted and Lewis acid catalysts such as CH3COOH (2.5-5.7 M), H3PO4 (15%), and Sc(OTf)3 (20% w:w), thus obtaining HMF (22%), AMF (38%), LA (25-46%), and furfural (22%) with good selectivity and under relatively mild conditions (T = 200 °C, time = 2 h). These final products can be employed in several chemical sectors, for example, as solvents, fuels, and for new materials as a monomer precursor. The characterization of matrices was accomplished by FTIR and LCSM analyses, demonstrating the influence of morphology on reactivity. The low e-factor values and the easy scale up render this protocol suitable for industrial applications.

Pd nanoparticle catalysed one-pot sequential Heck and Suzuki couplings of bromo-chloroarenes in ionic liquids and water.

Pd nanoparticles generated in green reaction media (viz. ionic liquids and water) catalyze the one-pot sequential Heck and Suzuki coupling reactions of bromo-chloroarenes to afford unsymmetrically substituted arenes in good yields.

Steel slag as low-cost catalyst for artificial photosynthesis to convert CO2 and water into hydrogen and methanol.

Photoreduction of CO2 with sunlight to produce solar fuels, also named artificial photosynthesis, is considered one of the most attractive strategies to face the challenge of reducing greenhouse gases and achieving climate neutrality. Following an approach in line with the principles of the circular economy, the low-cost catalytic system (1) based on an industrial by-product such as steel slag was assessed, which was properly modified with nanostructured palladium on its surface in order to make it capable of promoting the conversion of CO2 into methanol and hydrogen through a two-stage process of photoreduction and thermal conversion having formic acid as the intermediate. Notably, for the first time in the literature steel slag is used as photoreduction catalyst.

Special issue: nano-catalysts and nano-technologies for green organic synthesis.

Catalysis by transition-metal nanoparticles has undergone an explosive growth during the past decade. This special issue presents the general trends in the current research in this field, the present situation concerning scope and limitations, as well as the future perspectives. Original contributions are also presented on the applications of nano-catalysts to the green synthesis.

Valorization of cigarette butts for synthesis of levulinic acid as top value-added chemicals.

Unprecedented in the literature, levulinic acid (LA), one of the top value-added intermediates of chemical industry, is obtained from cigarette butts as cellulose feedstock by means of a one-pot hydrothermal process carried out at 200 °C for 2 h and catalysed by phosphoric acid. The protocol avoids the use of more aggressive and toxic H2SO4 and HCl, that are generally employed on several cellulose sources (e.g. sludge paper), thus minimizing corrosion phenomena of plants. Neither chemical pre-treatment of butts nor specific purification procedure of LA are required. Notably, by simply modifying acid catalyst (e.g. using CH3COOH), another top value-added fine chemical such as 5-hydroxymethylfuraldehyde (HMF) is obtained, thus widening the scope of the method. Being cigarette filters a waste available in quantities of megatonnes per year, they represent an unlimited at no cost source of cellulose, thus enabling the up-scale to an industrial level of LA production.

Concerning Synthesis of New Biobased Polycarbonates with Curcumin in Replacement of Bisphenol A and Recycled Diphenyl Carbonate as Example of Circular Economy.

Curcumin (CM) is a natural polyphenol wellknown for its antioxidant and pharmaceutical properties, that can represent a renewable alternative to bisphenol A (BPA) for the synthesis of biobased polycarbonates (PC). In the presented strategy, preparation of the CMbased PC was coupled with chemical recycling of the fossilbased BPA polycarbonate (BPAPC) conducting a twosteps transpolymerization that replaces BPA monomer with CM or its tetrahydrogenated colorless product (THCM). In the first step of synthetic strategy, depolymerization of commercial BPAPC was carried out with phenol as nucleophile, according to our previous procedure based on zinc derivatives and ionic liquids as catalysts, thus producing quantitatively diphenyl carbonate (DPC) e BPA. In the second step, DPC underwent a melt transesterification with CM or THCM monomers affording the corresponding biobased polycarbonates, CMPC and THCMPC, respectively. THCM was prepared by reducing natural bisphenol with cyclohexene as a hydrogen donor and characterized by 1H-NMR and MS techniques. Polymerization reactions were monitored by infrared spectroscopy and average molecular weights and dispersity of the two biobased polymers THCMPC and CMPC were determined by means of gel permeation chromatography (GPC). Optical properties of the prepared polymers were also measured.

Glucose as a clean and renewable reductant in the Pd-nanoparticle-catalyzed reductive homocoupling of bromo- and chloroarenes in water.

An efficient and highly sustainable Ullmann-type homocoupling of bromo- and chloroarenes, including the more challenging electron-rich chloroarenes (e.g., 4-chloroanisole), catalyzed by in situ generated Pd colloids, is carried out in aqueous medium under relatively mild conditions (temperatures ranging from 40 to 90 degrees C). Glucose is used as a clean and renewable reductant, while tetrabutylammonium hydroxide (TBAOH) acts as base, surfactant, and phase-transfer agent, creating a favorable environment for the catalyst. Pd nanoparticle sizes, morphology, and chemical composition are ascertained by TEM and XPS analyses.

Palladium/zirconium oxide nanocomposite as a highly recyclable catalyst for C-C coupling reactions in water.

Palladium nanoparticles have been electrochemically supported on zirconium oxide nanostructured powders and all the nanomaterials have been characterized by several analytical techniques. The Pd/ZrO(2) nanocatalyst is demonstrated to be a very efficient catalyst in Heck, Ullmann, and Suzuki reactions of aryl halides in water. The catalyst efficiency is attributed to the stabilization of Pd nanophases provided by tetra(alkyl)- ammonium hydroxide, which behaves both as base and PTC (phase transfer catalyst) agent.

Palladium-nanoparticle-catalysed Ullmann reactions in ionic liquids with aldehydes as the reductants: scope and mechanism.

An efficient Ullmann-type reductive homocoupling of aryl, vinyl and heteroaryl halides can be promoted by an aldehyde in tetraalkylammonium ionic liquids under very mild reaction conditions. This simple procedure generates symmetrical biaryls under relatively mild conditions. The ionic liquid is crucial for this process because it behaves simultaneously as a base, ligand and reaction medium. The role of the aldehyde is also discussed and a general mechanism for this unusual reaction is proposed. These results open the way to a new efficient method of Pd-catalysed dehydrogenation of carbonyl compounds.

Metronomic chemotherapy against cancer: from paradigm to clinical practice?

We describe two paradigmatic cases where metronomic antitumor chemotherapy was successfully employed in patients not suitable for standard treatments. The first patient was affected by advanced soft tissue sarcoma but she also had ischemic cardiopathy. She received oral cyclophosphamide 50 mg once daily and methotrexate 2.5 mg bid twice weekly, obtaining a significant clinical response with a progression-free survival of 7 months. The second patient was over 70 years of age and suffered from metastatic gastric cancer. Because of his poor performance status he was given capecitabine 1500 mg daily, achieving a complete remission with a current disease-free survival of 13 months. In both cases no significant toxicities were observed.