3D Printing with Biobased PEF for Carbon Neutral Manufacturing

Kucherov F.A., Gordeev E.G., Kashin A.S., Ananikov V. P., Angew. Chem. Int. Ed., 2017, 56, 15931 – 15935 .
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We demonstrate the utility of 100% biomass-derived poly(ethylene-2,5-furandicarboxylate) (PEF) as an efficient material for Fused Deposition Modeling (FDM) 3D printing. A complete cycle from cellulose to printed object has been performed. PEF-printed objects created in the present study demonstrated higher chemical resistance than objects printed with commonly available materials (ABS, PLA, PETG). The studied PEF polymer has shown key advantages for 3D printing: optimal adhesion, thermoplasticity, lack of delamination and low heat shrinkage. The high thermal stability of PEF and relatively low temperature that are necessary for extrusion are optimal for recycling printed objects and minimizing waste. Several successive cycles of 3D-printing and recycling were successfully demonstrated. The suggested approach for extending additive manufacturing to carbon neutral materials opens a new direction in the field of sustainable development.

Understanding Active Species in Catalytic Transformations: from Molecular Catalysis to Nanoparticles, Leaching, “Cocktails” of Catalysts and Dynamic Systems

Eremin D.B., Ananikov V.P., Coord. Chem. Rev., 2017, 346, 2-19.
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In the present review, we consider the transformations of molecular catalysts, leaching, aggregation and various interconversions of metal complexes, clusters and nanoparticles that occur during catalytic processes. The role of catalyst evolution and the mechanistic picture of "cocktail"-type systems are considered from the perspective of the development of a new generation of efficient, selective and re-usable catalysts for synthetic applications. Rational catalyst development and the improvement of catalyst performance cannot be achieved without an understanding of the dynamic nature of catalytic systems.

Biological Activity of Ionic Liquids and Their Application in Pharmaceutics and Medicine

Egorova K.S., Gordeev E.G., Ananikov V.P., Chem. Rev., 2017, 117, 7132–7189.
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Ionic liquids are remarkable chemical compounds, which find applications in many areas of modern science. Because of their highly tunable nature and exceptional properties, ionic liquids have become essential players in the fields of synthesis and catalysis, extraction, electrochemistry, analytics, biotechnology, etc. Apart from physical and chemical features of ionic liquids, their high biological activity has been attracting significant attention from biochemists, ecologists, and medical scientists. This Review is dedicated to biological activities of ionic liquids, with a special emphasis on their potential employment in pharmaceutics and medicine. The accumulated data on the biological activity of ionic liquids, including their antimicrobial and cytotoxic properties, are discussed in view of possible applications in drug synthesis and drug delivery systems. Dedicated attention is given to a novel active pharmaceutical ingredient-ionic liquid (API-IL) concept, which suggests using traditional drugs in the form of ionic liquid species. The main aim of this Review is to attract a broad audience of chemical, biological, and medical scientists to study advantages of ionic liquid pharmaceutics. Overall, the discussed data highlight the importance of the research direction defined as "Ioliomics", studies of ions in liquids in modern chemistry, biology, and medicine.

A Solid Acetylene Reagent with Enhanced Reactivity: Fluoride-Mediated Functionalization of Alcohols and Phenols

Werner G., Rodygin K.S., Kostin A.A., Gordeev E.G., Kashin A.S., Ananikov V.P., Green Chem., 2017, 19, 3032-3041.
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The direct vinylation of an OH group in alcohols and phenols was carried out utilizing a novel CaC 2/KF solid acetylene reagent in a simple K2CO3/KOH/DMSO system. The functionalization of a series of hydroxyl-group-containing substrates and the post-modification of biologically active molecules were successfully performed using standard laboratory equipment, providing straightforward access to the corresponding vinyl ethers. The overall process developed involves an atom-economical addition reaction employing only inorganic reagents, which significantly simplifies the reaction set-up and the isolation of products. A mechanistic study revealed a dual role of the F additive, which both mediates the surface etching/renewal of the calcium carbide particles and activates the C[triple bond, length as m-dash]C bond towards the addition reaction. The development of the fluoride-mediated nucleophilic addition of alcohols eliminates the need for strong bases and may substantially extend the areas of application of this attractive synthetic methodology due to increasing functional group tolerance. As a replacement for dangerous and difficult to handle high-pressure acetylene, we propose the solid reagent CaC2/KF, which is easy to handle, does not require dedicated laboratory equipment and demonstrates enhanced reactivity of the acetylenic triple bond. Theoretical calculations have shown that fluoride-mediated activation of the hydroxyl group towards nucleophilic addition significantly reduces the activation barrier and facilitates the reaction.

Efficient Route for the Construction of Polycyclic Systems from Bioderived HMF

Kucherov F.A., Galkin K.I., Gordeev E.G., Ananikov V.P., Green. Chem., 2017, 19, 4858-4864.
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The first synthesis of tricyclic compounds from biobased 5-hydroxymethylfurfural (HMF) is described. The Diels-Alder reaction was used to implement the transition from HMF to non-planar framework, which possessed the structural cores of naturally occurring biologically active compounds and building blocks of advanced materials. A one-pot, three-step sustainable synthesis in water was developed starting directly from HMF. The reduction of HMF led to 2,5-bis(hydroxymethyl)furan (BHMF), which could be readily involved in the Diels-Alder cycloaddition reaction with HMF-derived maleimide, followed by hydrogenation of the double bond. The described transformation was diastereoselective and proceeded with a good overall yield. The applicability of the chosen approach for the synthesis of analogous structures containing amine functionality on the side chain was demonstrated. To produce the target compounds, only platform chemicals were used with carbohydrate biomass as the single carbon source.

Dynamic Behavior of Metal Nanoparticles in Pd/C and Pt/C Catalytic Systems under Microwave and Conventional Heating

Pentsak E.O., Cherepanova V.A., Ananikov V.P., ACS Appl. Mater. Interfaces., 2017, 9, 36723–36732.
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Metal on carbon catalysts (M/C) are ubiquitously used in modern research and industry to carry out a variety of chemical transformations. Stable metal-support frameworks and inertness of the carbon materials are usually taken for granted in these very useful catalytic systems. Initially, the present study was aimed to increase the efficiency of Pd/C and Pt/C catalytic systems under microwave and conventional heating. Interestingly, a dynamic behavior of the metal nanoparticles was revealed, and a series of carbon support transformations occurred during the thermal treatments of the catalysts. Microwave and thermal heating of the M/C catalysts resulted in substantial transformations of the carbon supports via the formation of pits, trenches, nanofibers and nanowalls. Detailed studies with field-emission scanning electron microscopy was carried out involving statistical averaging over large surface areas. The effects of the dynamic behaviors of the supported metal particles on the catalytic activities of the synthetically useful Mizoroki-Heck and Suzuki-Miyaura reactions were demonstrated. Revealed dynamic behavior and modification of the carbon support due to microwave treatment were observed in a number of M/C systems (M = Pd, Pt, Ni, Co, Сu, Fe and Au).

Rapid 'Mix-and-Stir' Preparation of Well-defined Pd/C Catalysts for Efficient Practical Usage

Yakukhnov S. A., Pentsak E. O., Galkin K. I., Mironenko R. M., Drozdov V. A., Likholobov V. A., Ananikov V. P., ChemCatChem, 2017, ASAP.
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A facile direct deposition approach for the preparation of recyclable Pd/C catalysts simply by stirring a solution of Pd2dba3 with a suitable carbon material was evaluated. An extraordinary rapid catalyst preparation procedure (< 5 min) under mild conditions and its excellent performance in cross-coupling and hydrogenation reactions were demonstrated. The key point for catalyst design was to directly deposit Pd(0) centers onto highly accessible surface area and to avoid ill-defined Pd(II)/Pd(0) states.

A New Mode of Operation of Pd-NHC Systems Studied in a Catalytic Mizoroki–Heck Reaction

Astakhov A.V., Khazipov O.V., Chernenko A.Yu., Pasyukov D.V., Kashin A.S., Gordeev E.G., Khrustalev V.N., Chernyshev V.M., Ananikov V.P., Organometallics, 2017, 36, 1981-1992.
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Metal complexes bearing N-heterocyclic carbene (NHC) ligands are typically considered the system of choice for homogeneous catalysis with well-defined molecular active species due to their stable metal–ligand framework. A detailed study involving 19 different Pd-NHC complexes with imidazolium, benzimidazolium, and triazolium ligands has been carried out in the present work and revealed a new mode of operation of metal-NHC systems. The catalytic activity of the studied Pd-NHC systems is predominantly determined by the cleavage of the metal–NHC bond, while the catalyst performance is strongly affected by the stabilization of in situ formed metal clusters. In the present study, the formation of Pd nanoparticles was observed from a broad range of metal complexes with NHC ligands under standard Mizoroki–Heck reaction conditions. A mechanistic analysis revealed two different pathways to connect Pd-NHC complexes to "cocktail"-type catalysis: (i) reductive elimination from a Pd(II) intermediate and the release of NHC-containing byproducts and (ii) dissociation of NHC ligands from Pd intermediates. Metal-NHC systems are ubiquitously applied in modern organic synthesis and catalysis, while the new mode of operation revealed in the present study guides catalyst design and opens a variety of novel opportunities. As shown by experimental studies and theoretical calculations, metal clusters and nanoparticles can be readily formed from M-NHC complexes after formation of new M–C or M–H bonds followed by C–NHC or H–NHC coupling. Thus, a combination of a classical molecular mode of operation and a novel cocktail-type mode of operation, described in the present study, may be anticipated as an intrinsic feature of M-NHC catalytic systems.

Influence of R–NHC Coupling on the Outcome of R–X Oxidative Addition to Pd/NHC Complexes (R = Me, Ph, Vinyl, Ethynyl)

Gordeev E.G., Eremin D.B., Chernyshev V.M., Ananikov V.P., Organometallics, 2017, ASAP.
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Oxidative addition of organic halides (R–X) to (NHC)Pd0L complexes is involved in numerous metal-catalyzed reactions, and this step is expected to afford (NHC)PdII(R)(X)L intermediate complexes. However, these complexes may undergo further transformation via R–NHC coupling, which removes the NHC ligands from the metal and results in the generation of "bare" NHC-free metal species. The comparative theoretical study carried out in the present work revealed that the kinetic and thermodynamic stability of the (NHC)PdII(R)(X)L oxidative addition intermediates depends strongly on the nature of the organic group R. The predicted reactivity in the R–NHC coupling process decreases in the following order: R = Vinyl > Ethynyl > Ph > Me. Accordingly, for R = Me, a classical (NHC)PdII(R)(X)L intermediate can be expected as a product of the oxidative addition step, whereas for R = Ph, the outcome of the oxidative addition may already contain the NHC-free palladium complex. For R = Ethynyl, comparable amounts of both complexes should be formed, while for R = Vinyl, the NHC-free palladium complex can be the major product of the oxidative addition process. Unusual thermodynamic and kinetic instability of the (NHC)Pd(vinyl)(X)L complex and the tendency to vinyl–NHC coupling predicted by the computational modeling has been confirmed by experimental measurements with online mass spectrometric reaction monitoring. Thus, the outcome of the oxidative addition strongly depends on the type of organic group R and the R–NHC coupling process greatly influences the activity and stability of metal catalysts.

Toxicity of Metal Compounds: Knowledge and Myths

Egorova K.S., Ananikov V.P., Organometallics, 2017, 36, 4071-4090.
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Organometallic reagents and metal catalysts are used ubiquitously in academia and industry. Not surprisingly, the biological activity and environmental danger of metal compounds have become topics of outstanding importance. In spite of the rapid development of toxicology during the last decades, several common historically established "beliefs" are still frequently circulating in the organometallic community. In this Tutorial, we discuss existing opinions concerning (1) possibilities of toxicity measurements, (2) high toxicities of heavy-metal compounds, (3) correlation between the structure of a metal compound and its toxicity, (4) biological effect of direct/indirect contacts with metal compounds, and (5) dangers of metal nanoparticles. Basic concepts of toxicity studies and known data are described in the Tutorial step by step upon discussion of these issues. The main goal of this Tutorial is to demonstrate that the toxicity of a metal cannot be regarded as a constant property, since it depends on the oxidation state, ligands, solubility, morphology of particles, properties of the environment, and several other factors. As far as such chemically labile species as metal compounds are concerned, the nature of biological effects should not be assumed or taken for granted; indeed, reliable conclusions cannot be made without dedicated measurements.

Investigation of Cytotoxic Activity of Mitoxantrone at the Individual Cell Level by Using Ionic-Liquid-Tag-Enhanced Mass Spectrometry

Kucherov F. A., Egorova K. S., Posvyatenko A. V., Eremin D. B., Ananikov V. P., Anal. Chem., 2017, 89, 13374−13381.
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A novel mitoxantrone conjugate was synthesized by coupling mitoxantrone with ionic liquid tags, and cytotoxic behavior of the designed conjugate was studied in normal and cancer cell lines. The synthesized mitoxantrone conjugate was oil at physiological temperatures and demonstrated high aqueous solubility. Sensitivity of electrospray ionization mass spectrometry (ESI-MS) to the mitoxantrone conjugate was improved by an order of magnitude, in comparison with original mitoxantrone dihydrochloride. The observed ESI-MS signals were shifted to a "clearer" lower-mass region of the spectrum, which allowed investigation of the drug at the level of individual cells. The ionic liquid tags proposed in the present work consist of an easily available imidazolium salt residue and show a number of key advantages from the points of view of drug conjugate synthesis, drug delivery and analytic detection.

Micro-Scale Processes Occurring in Ionic Liquid–Water Phases During Extraction

Seitkalieva M. M., Kashin A. S., Egorova K. S., Ananikov V. P., Sep. Purif. Technol., 2017, ASAP.
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For the first time, extraction process in ionic liquids was visualized by direct electron microscopy observation. Microscopy images revealed the micro-heterogeneous nature of the studied extraction systems. Depending on the nature of ionic liquids and studied compounds, four main micro-scale areas were observed: a) uniform homogeneous phase; b) microcompartments in the liquid phase; c) solid microinclusions on the phase boundary; and d) solid microinclusions inside the separated microphases. The microscopic monitoring showed stepwise sequence of the extraction process, and the retention ability of the ionic liquid–water system decreased in the following order: homogeneous phase > microcompartments > solid microinclusions.

Substrate-Selective C−H Functionalization for the Preparation of Organosulfur Compounds from Crude Oil-Derived Components

Luzyanin K.V., Marianov A.N., Kislitsyn P.G., Ananikov V.P., ACS Omega, 2017, 2, 1419–1423.
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The direct utilization of a natural feedstock in organic synthesis is an utmost challenge because the selective production of one product from a mixture of starting materials requires unprecedented substrate selectivity. In the present study, a simple and convenient procedure is evaluated for the substrate-selective alkenylation of a single component in a mixture of organosulfur compounds. Pd-catalyzed alkenylation of two-, three-, four-, and five-component mixtures of crude oil-derived sulfur species led to the exclusive C−H functionalization of only one compound. The observed remarkable substrate selectivity opens new opportunities for sustainable organic synthesis.

Alkynylation of Bio-Based HMF to Connect Biomass Processing with Conjugated Polymers and Furanic Pharmaceuticals

Romashov L.V., Ananikov V.P.,, Chem. Asian J., 2017, 12, 2652 –2655.
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Acetylene-functionalized platform chemicals were synthesized for the first time based on biomass-derived 5-hydrohymethylfurfural (HMF). Demanded mono- and bis-ethynylfurans were obtained in high yields (89-99%). Plausible application of these products in the synthesis of smart organic conjugated materials and pharmaceuticals was addressed in a series of transformations. Conjugated polyacetylenic polymers with morphology control have been prepared with the incorporation of the HMF core.

Plant Biomass Conversion to Furan Derivatives and Sustainable Access to the New Generation of Polymers, Functional Materials and Fuels

Chernyshev V.M., Kravchenko O.A., Ananikov V.P., Russ. Chem. Rev., 2017, 86, 357 – 387.
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5-Hydroxymethylfurfural (HMF) is an important versatile reagent, a so-called platform chemical, that can be produced from plant biomass compounds: hexose carbohydrates and lignocellulose. In the near future, HMF and its derivatives could become an alternative feedstock for the chemical industry and replace, to a great extent, non-renewable sources of hydrocarbons (oil, natural gas and coal). This review analyzes recent advances in the synthesis of HMF from plant feedstocks and considers the prospects for the use of HMF in the production of monomers and polymers, porous carbon materials, engine fuels, solvents, pharmaceuticals, pesticides and chemicals. The most important HMF derivatives considered in the review include 2,5-furandicarboxylic acid, 2,5-diformylfuran, 2,5-bis(hydroxymethyl)furan, 2,5-bis(aminomethyl)furan, 2,5-dimethylfuran, 2,5-dimethyltetrahydrofuran, 2,5-bis(methoxymethyl)furan, and 5-ethoxymethylfurfural. In the nearest future, a significant extension of the HMF application is expected, and this platform chemical may be considered a major source of carbon and hydrogen for the chemistry of the 21st century.