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International audience; The partial reduction of amides is a challenging transformation that must overcome the intrinsic stability of the amide bond and exhibit high chemoselective control to overcome overreduction to amine products. To address this challenge, we describe a zirconium-catalysed synthesis of imines by the reductive deoxygenation of secondary amides. This reaction exploits the excellent chemoselectivity of Schwartz’s reagent (Cp 2 Zr(H)Cl) and utilises (EtO) 3 SiH as a mild stoichiometric reductant to enable catalyst turnover. The reaction generally proceeds with high yields (19 examples, 51 to 95% yield) and tolerates a variety of functional groups (alkene, ester, nitro, etc.). Stoichiometric mechanistic investigations suggest the regeneration of the active [Zr]–H catalyst is achieved through the metathesis of Si–H and Zr–OR σ-bonds.

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Mixing biomasses has a good potential to solve operational problems related to ash behavior in thermochemical valorization processes. Chemical reactions within the ash of the blend, and not only a mixing effect without reaction, need to take place to form new solid phases in the mixture at the expense of getting rid of the problematic liquid phase to decrease the slagging tendency. In addition, instead of random/proportion mixing, process simulation approaches based on thermodynamics calculations can provide good capabilities to predict the ash behavior of biomasses and their mixtures.The present work had three main objectives. First, it focused on validating the presence of a chemical reaction in comparison with a simple mixing effect within the ash of biomass mixtures. Then, it aimed to assess the capabilities of thermodynamic approaches to predict the ash behavior of biomass and their blends, compared with experimental data; and to highlight possible improvements. Finally, several thermodynamic properties were investigated and improvements to the thermodynamic database were proposed.Various oak barks, wheat straws, and their mixtures were used in combustion laboratory furnaces and pilot scale reactors (boilers and fluidized bed). The operating conditions were varied in laboratory furnaces to study their effects on the reactivity of the ash within the mixtures. For thermodynamic calculations and simulations, two commercial thermodynamic databases, FToxid and GTOX, were used with the FactSage Gibbs energy minimization software.The mixing without reaction effect was more evident when biomass pellets were used on both laboratory and pilot scales. In this case, the simple mixing rule was roughly able to simulate the general ash behavior of biomass mixture. However, chemical reactions effect was dominant when mixtures of compressed ash of biomass were used. Solid crystalline phases K2Ca2Si2O7 and K2Ca6Si4O15 were the direct products of these chemical reactions. Their relative proportion was inversely proportional to the problematic amorphous phase in the final ash produced. Once the reactor cools down, this phase, which contains ash in the molten liquid phase, solidifies and blocks the combustion furnaces. These two compounds were mostly stable at 1000℃, at which equilibrium was reached after 6h. However, they existed at a lower proportion at 850℃ and disappeared at 1200℃.The developed laboratory pellet test was able to predict efficiently the pilot ash behavior of both individual biomasses and their mixture in terms of crystalline and amorphous mineralogical composition in a quantitative way along with agglomeration distribution. The phase diagram approach also showed good capabilities in predicting the physical state of the ash (solid, liquid, or solid-liquid mixture) using both databases. Global simulations using the FToxid database showed better prediction capabilities for single biomass ash than the ones using the GTOX database. In the case of blends, global simulations using the FToxid dataset were significantly limited; and those using the GTOX dataset did not give satisfactory results. Both databases showed correct volatilization prediction capabilities but failed to forecast the characteristic temperatures of the solidus and liquidus.To improve the thermodynamic database, three ternary compounds K2Ca2Si2O7, K2Ca6Si4O15, and K4CaSi3O9 were synthesized. Their melting points and enthalpies of formation were measured. The Cp of the stoichiometric intermediate compounds in the binary K2O-SiO2 were also remodeled based on the 3rd generation CalPhad Einstein model using experimental and DFT calculated heat capacities. An updated and more accurate version for the calculated K2O-SiO2 phase diagram (solid only) was presented.; Les mélange des biomasses ont un bon potentiel pour résoudre les problèmes opérationnels liés au comportement des cendres dans les procédés de valorisation thermochimique. Des réactions chimiques au sein des cendres du mélange, et pas seulement un effet de dilution, doivent avoir lieu pour former de nouvelles phases solides dans le mélange pour éliminer la phase liquide problématique. De plus, au lieu d'un mélange aléatoire/proportionnel, les approches de simulation de processus basées sur des calculs thermodynamiques peuvent fournir de bonnes capacités pour prédire le comportement des cendres des biomasses et de leurs mélanges.Le présent travail avait trois objectifs principaux. Dans un premier temps, il s'est attaché à valider la présence d'une réaction chimique par rapport à un simple effet de dilution au sein des cendres des mélanges de biomasse. Ensuite, il s'agissait d'évaluer les capacités des approches thermodynamiques à prédire le comportement des cendres de la biomasse et de leurs mélanges, par rapport aux données expérimentales ; et de mettre en évidence les améliorations possibles. Enfin, plusieurs améliorations liées à la base de données thermodynamique ont été proposées.Diverses écorces de chêne, pailles de blé et leurs mélanges ont été utilisés dans des fours de laboratoire à combustion et des réacteurs pilotes (chaudières et lit fluidisé). Les conditions opératoires ont été variées dans des fours de laboratoire pour étudier leurs effets sur la réactivité des cendres au sein des mélanges. Pour les calculs et les simulations thermodynamiques, deux bases de données thermodynamiques commerciales, FToxid et GTOX, ont été utilisées avec le logiciel de minimisation d'énergie FactSage Gibbs.L’effet de dilution était plus évident lorsque les granulés de biomasse étaient utilisés à la fois à l'échelle du laboratoire et à l'échelle pilote. Dans ce cas, la règle de mélange était à peu près capable de simuler le comportement général des cendres. Cependant, l'effet des réactions chimiques était dominant lorsque des mélanges de cendres comprimées de biomasse étaient utilisés. Les phases cristallines solides K2Ca2Si2O7 et K2Ca6Si4O15 sont les produits directs. Leur proportion relative était inversement proportionnelle à la phase amorphe problématique. Ils étaient stables à 1000℃, à laquelle l'équilibre a été atteint après 6h. Cependant, ils existaient en moindre proportion à 850℃ et disparaissaient à 1200℃.Le ‘pellet test’ sur des granules de biomasses a pu prédire le comportement des cendres a échelle pilote. L'approche du diagramme de phase a également montré de bonnes capacités de prédiction de l'état physique des cendres (solide, liquide ou mélange solide-liquide) en utilisant les deux bases de données. Les simulations globales utilisant la base de données FToxid ont montré de meilleures capacités de prédiction pour les cendres de biomasse unique que celles utilisant la base de données GTOX. Dans le cas des mélanges, les simulations globales utilisant l'ensemble de données FToxid étaient considérablement limitées ; et ceux utilisant la base de données GTOX n'ont pas donné de résultats satisfaisants. Les deux bases de données ont montré des capacités de prédiction de volatilisation correctes mais n'ont pas réussi à prévoir les températures caractéristiques du solidus et du liquidus.Pour améliorer la base de données thermodynamique, trois composés ternaires K2Ca2Si2O7, K2Ca6Si4O15 et K4CaSi3O9 ont été synthétisés. Plusieurs de leurs propriétés thermodynamiques ont été mesurées. Les composés intermédiaires stœchiométriques dans le binaire K2O-SiO2 ont également été remodelés par le modèle CalPhad Einstein de 3eme génération en utilisant des capacités thermiques expérimentales et calculées par DFT. Une version mise à jour et plus précise du diagramme de phase K2O-SiO2 calculé (solide uniquement) a été présentée.

Chemically modified oligonucleotides have advanced as important therapeutic tools as reflected by the recent advent of mRNA vaccines and the FDA-approval of various siRNA and antisense oligonucleotides. These sequences are typically accessed by solid-phase synthesis which despite numerous advantages is restricted to short sequences and displays a limited tolerance to functional groups. Controlled enzymatic synthesis is an emerging alternative synthetic methodology that circumvents the limitations of traditional solid-phase synthesis. So far, most approaches strived to improve controlled enzymatic synthesis of canonical DNA and no potential routes to access xenonucleic acids (XNAs) have been reported. In this context, we have investigated the possibility of using phosphate as a transient protecting group for controlled enzymatic synthesis of DNA and locked nucleic acid (LNA) oligonucleotides. Phosphate is ubiquitously employed in natural systems and we demonstrate that this group displays most characteristics required for controlled enzymatic synthesis. We have devised robust synthetic pathways leading to these challenging compounds and we have discovered a hitherto unknown phosphatase activity of various DNA polymerases. These findings open up directions for the design of protected DNA and XNA nucleoside triphosphates for controlled enzymatic synthesis of chemically modified nucleic acids.

National audience; Cyclodextrins are cage-shaped molecules having the remarkable ability to trap smaller compounds, and have thus led to applications in many disciplines such as medicine to increase the bioavailability of hydrophobic drugs. This historical review summarizes the outstanding contribution of the late Professor Benito Casu to cyclodextrin research and, more generally, to the chemistry and biochemistry of linear and cyclic oligosaccharides, polysaccharides, glycosaminoglycans, and heparin. Professor Casu was the first to elucidate the structure and conformations of cyclodextrins by infrared spectroscopy and proton nuclear magnetic resonance (NMR). In particular, he showed that trapped compounds induced a shift of H peaks in NMR due to the shielding effect of cyclodextrins. He also demonstrated that the d-glucopyranose cyclodextrin units are in the C-1 chair conformation by analyzing α-cyclodextrin by NMR in dimethylsulfoxide-d6.

International audience; Actin is among the most abundant proteins in eukaryotic cells and assembles into dynamic filamentous networks regulated by many actin binding proteins. The actin cytoskeleton must be finely tuned, both in space and time, to fulfill key cellular functions such as cell division, cell shape changes, phagocytosis and cell migration. While actin oxidation by reactive oxygen species (ROS) at non-physiological levels are known for long to impact on actin polymerization and on the cellular actin cytoskeleton, growing evidence shows that direct and reversible oxidation/reduction of specific actin amino acids plays an important and physiological role in regulating the actin cytoskeleton. In this review, we describe which actin amino acid residues can be selectively oxidized and reduced in many different ways (e.g. disulfide bond formation, glutathionylation, carbonylation, nitration, nitrosylation and other oxidations), the cellular enzymes at the origin of these post-translational modifications, and the impact of actin redox modifications both in vitro and in vivo. We show that the regulated balance of oxidation and reduction of key actin amino acid residues contributes to the control of actin filament polymerization and disassembly at the subcellular scale and highlight how improper redox modifications of actin can lead to pathological conditions.

International audience; Emollient oils are ubiquitous ingredients of personal care products, especially skin care and hair care formulations. They offer excellent spreading properties and give end-use products a soft, pleasant and non-sticky after-feel. Emollients belong to various petro- or bio-based chemical families among which silicone oils, hydrocarbons and esters are the most prominent. Silicones have exceptional physicochemical and sensory properties but their high chemical stability results in very low biodegradability and a high bioaccumulation potential. Nowadays, consumers are increasingly responsive to environmental issues and demand more environmentally friendly products. This awareness strongly encourages cosmetics industries to develop bio-based alternatives to silicone oils. Finding effective silicon-free emollients requires understanding the molecular origin of emollience. This review details the relationships between the molecular structures of emollients and their physicochemical properties as well as the resulting functional performances in order to facilitate the design of alternative oils with suitable physicochemical and sensory properties. The molecular profile of an ideal emollient in terms of chemical function (alkane, ether, ester, carbonate, alcohol), optimal number of carbons and branching is established to obtain an odourless oil with good spreading on the skin. Since none of the carbon-based emollients alone can imitate the non-sticky and dry feel of silicone oils, it is judicious to blend alkanes and esters to significantly improve both the sensory properties and the solubilizing properties of the synergistic mixture towards polar ingredients (sun filters, antioxidants, fragrances). Finally, it is shown how modelling tools (QSPR, COSMO-RS and neural networks) can predict in silico the key properties of hundreds of virtual candidate molecules in order to synthesize only the most promising whose predicted properties are close to the specifications.

International audience; The synthesis and characterization of a polyrotaxanated covalent organic network (CON) based on the association between the viologen and pillar[5]arene (P[5]OH) units are reported. The mechanical bond allows for the irreversible insertion of n-type redox centers (P[5]OH macrocycles) within a pristine structure based on p-type viologen redox centers. Both redox units are active on a narrow potential range and, in water, the presence of P[5]OH greatly increases the electroactivity of the material.

International audience; The regioselective iodination of different 2-mono-, 3-mono- and 2,3-disubstituted 6-aminoquinoxalines, which takes place at their 5-position, was rationalized on the basis of Hückel theory calculations. Oxazolo- and thiazolo[5,4-f]quinoxaline analogues of reported disease-related protein kinases inhibitors were synthesized from the obtained 6-amino-5-iodoquinoxalines by using as key step copper-catalyzed azole ring formation. Pyrazino[b,e]isatins were obtained, for the first time, from the same substrates by recourse to Sonogashira coupling, alkyne hydration, and oxidative cyclization. The absorption and emission properties of the most promising compounds were recorded. In addition, most of the synthesized polycycles were evaluated as protein kinase inhibitors and for their antiproliferative activity towards cancer cells.

International audience; Regioselective access to heterohelicenes through the 1,3-dipolar cycloaddition of sydnones with arynes is described. Novel access to sydnones and poly(hetero)aromatic aryne precursors allowed the introduction of chemical diversity over multiple positions of the helical scaffolds. The origins of the unconventional regioselectivity during the cycloaddition steps was systematically investigated using density functional theory (DFT) calculations, unveiling the key features that control this reactivity, namely, face-to-face ($\pi \cdot \cdot \cdot \pi$) or edge-to-face (C−H$\cdot \cdot \cdot \pi$) interactions, primary orbital interactions and distortion from coplanarity in the transition structures (TSs) of the transformation. From the library of 24 derivatives synthesized, a pyridyl containing derivative displayed reversible, red-shifted, pH-triggered chiroptical switching properties, with CPL-sign reversal. It is found that protonation of the helicene causes a change of the angle between the electric and magnetic dipole moments related to the S$_1$ → S$_0$ transition, resulting in this rare case of reversible CPL sign inversion upon application of an external stimulus.

fff; International audience; Identifying the structure of the most active site is essential to improve the performance of supported metal catalysts. For structure-sensitive reactions, in silico design cannot be easily achieved combining the scaling relations and Brønsted–Evans–Polanyi relations, which are only built on energy-based descriptors. We used here the generalized coordination number as a structural descriptor and established that low-coordinated sites are desirable when using Co and Cu to perform the acceptor-less alcohol dehydrogenation reaction.

International audience; This work reports on the preparation and structural characterization of flavo[7]helicene 1 (flavin-[7]helicene conjugate), which was subsequently characterized at the molecular level in either an aqueous environment or an organic phase, at the supramolecular level in the form of polymeric layers, and also embedded in a lipidic mesophase environment to study the resulting properties of such a hybrid relative to its parent molecules. The flavin benzo[g]pteridin-2,4-dione (isoalloxazine) was selected for conjugation because of its photoactivity and reversible redox behavior. Compound 1 was prepared from 2-nitroso[6]helicene and 6-methylamino-3-methyluracil, and characterized using common structural and spectroscopic tools: circular dichroism (CD), circularly polarized luminescence (CPL) spectroscopy, cyclic voltammetry (CV), and DFT quantum calculations. In addition, a methodology that allows the loading of 1 enantiomers into an internally nanostructured lipid (1-monoolein) matrix was developed.

Candida albicans mannan consists of a large repertoire of oligomannosides with different types of mannose linkages and chain lengths, which act as individual epitopes with more or less overlapping antibody specificities. Although anti-C. albicans mannan antibody levels are monitored for diagnostic purposes nothing is known about the qualitative distribution of these antibodies in terms of epitope specificity. We addressed this question using a bank of previously synthesized biotin sulfone tagged oligomannosides (BSTOs) of α and β anomery complemented with a synthetic β-mannotriose described as a protective epitope. The reactivity of these BSTOs was analyzed with IgM isotype monoclonal antibodies (MAbs) of known specificity, polyclonal sera from patients colonized or infected with C. albicans, and mannose binding lectin (MBL). Surface plasmon resonance (SPR) and multiple analyte profiling (MAP) were used. Both methods confirmed the usual reactivity of MAbs against either α or β linkages, excepted for MAb B6.1 (protective epitope) reacting with β-Man whereas the corresponding BSTO reacted with anti-α-Man. These results were confirmed in western blots with native C. albicans antigens. Using patients’ sera in MAP, a significant correlation was observed between the detection of anti-mannan antibodies recognizing β- and α-Man epitopes and detection of antibodies against β-linked mannotriose suggesting that this epitope also reacts with human polyclonal antibodies of both specificities. By contrast, the reactivity of human sera with other α- and β-linked BSTOs clearly differed according to their colonized or infected status. In these cases, the establishment of an α/β ratio was extremely discriminant. Finally SPR with MBL, an important lectin of innate immunity to C. albicans, classically known to interact with α-mannose, also interacted in an unexpected way with the protective epitope. These cumulative data suggest that structure/activity investigations of the finely tuned C. albicans anti-mannose immune response are worthwhile to increase our basic knowledge and for translation in medicine.

International audience; Platform molecules were defined by the US Department of Energy, as bio-based or bio-derived chemicals whose constituting elements totally originated from biomass and could be used as building blocks for the production of commodity and refined chemicals. These chemicals can subsequently be converted into a number of high-value bio-based chemicals or materials. Today, there is a growing urge for the discovering of a cheaper and cleaner way for the environment to produce platform molecules from renewable substrate such as carbon. Succinic acid (SA) is considered as a key platform chemical since it is used as a precursor for other valuable chemicals and has aroused interest worldwide with its wide applications. This review aims at highlighting the currently available information about the mechanisms involved in the production of platform molecules, especially the SA production. In this review, the processing technologies used in the production of platform molecules are described, in addition to the information regarding the optimization of key parameters, the mechanisms of genetic engineering and finally the redox potential and purification processes which are known as alternative cost-competitive providers of fossil fuels.

International audience; Oxidative isocyanide-based multicomponent reactions (oxidative IMCRs) are very useful tools for the rapid construction of molecular diversity starting from readily available and stable substrates. Despite all their benefits, such multicomponent reactions are underdeveloped and strictly limited to 3component processes. Indeed, in the presence of several reaction partners, the oxidation event needs to be rigorously chemoselective, which becomes incredibly more intricate as the number of reactive components increases. Nonetheless, we could overcome this significant pitfall and reach the first oxidative Ugi-type 4-IMCR by capitalizing on a very mild and green TEMPO-catalyzed electro-oxidation process. Employing alcohols as aldehyde surrogates and in the notable absence of any supporting electrolyte, this transformation proved to be extremely chemoselective in the presence of an amine and was compatible with a wide range of alcohols, amines, isocyanides, and carboxylic acids.

International audience; A catalytic intermolecular amination of non-activated tertiary C(sp 3)−H bonds (BDE of 96 kcal.mol-1) is reported for substrates displaying an activated benzylic site (BDE of 85 kcal.mol-1). The tertiary C(sp 3)−H bond is selectively functionalized to afford a,a,a-trisubstituted amides in high yields. This unusual site-selectivity results from the synergistic combination of Rh2(Stfpttl)4, a rhodium(II) complex with a well-defined catalytic pocket, with tert-butylphenol sulfamate (TBPhsNH2), which leads to a discriminating rhodium-bound nitrene species under mild oxidative conditions. This catalytic system is very robust and the reaction was performed on a 50 mmoles-scale with only 0.01 mol% of catalyst. The TBPhs group can be removed under mild conditions to afford the corresponding NH-free amines.

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International audience; Ramie plants (Boehmeria nivea) have been cultivated on ion-adsorption rare earth elements (REEs) mine tailings and showed a low ability to accumulate REEs, especially in the stems (REE= 24±17 mg kg-1) with higher concentration in leaves and roots (REE= 57 to 66 mg kg-1). Ramie individual fibers were isolated using three degumming processes: a traditional alkali treatment (AT), a steam explosion (SE) treatment after a neutral (SEN) or after a basic (SEB) impregnation. Cellulose-rich (> 80%) fine fibers with very low amounts of non-cellulosic sugars (

The hemilabile Ad2P(o-C6H4)NMe2 ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold. The reaction is general. It works with a broad range of substrates of various electronic bias and steric demand, and proceeds with complete retention of stereochemistry from Z and E vinyl iodides. Both alkynyl and vinyl iodides react faster than aryl iodides. The elementary step is amenable to catalysis. Oxidative addition of vinyl iodides to gold and π-activation of alkenols (and N-alkenyl amines) at gold have been combined to achieve hetero-vinylation reactions. A number of functionalized heterocycles, i.e. tetrahydrofuranes, tetrahydropyranes, oxepanes and pyrrolidines were obtained thereby (24 examples, 87% average yield). Taking advantage of the chemoselectivity for vinyl iodides over aryl iodides, sequential transformations involving first a hetero-vinylation step and then a C–N coupling, a C–C coupling or an heteroarylation were achieved from a vinyl/aryl bis-iodide substrate., The hemilabile Ad2P(o-C6H4)NMe2 ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold.

International audience; Carbonylation reactions that generate high-value chemical feedstocks are integral to the formation of many industrially significant compounds. However, these processes require the use of CO, which is invariably derived from fossil-fuelreforming reactions. CO may also be generated through the electroreduction of CO2, but the coupling of these two processes is yet to be considered. Merging electrocatalytic reduction of CO2 to CO with thermocatalytic use of CO would expand the range of the chemicals produced from CO2. This work describes for the first time the development of a system coupling a high-pressure CO2 electrolytic cell containing a bimetallic ZnAg catalyst at the cathode for production of CO with a reactor with a faradaic efficiency of >90 % where high pressure CO is used for carbonylating propylene oxide into β-butyrolactone by thermal catalysis, the latter step having a reaction yield above 80%. While the production of monomers and polymers from CO2 is currently limited to organic carbonates, this strategy opens up the access to lactones from CO2, for the formation of polyesters.

Mesomorphous butterfly-like shape molecules based on benzodithiophene, benzodithiophene-4,8-dione and cyclopentadithiophen-4-one core moieties were efficiently synthesized by the Suzuki-Miyaura coupling and Scholl oxidative cyclo-dehydrogenation reactions' tandem. Most of the butterfly molecules spontaneously self-organize into columnar hexagonal mesophase. The electron-deficient systems possess strong solvent-gelling ability but are not luminescent, whereas the electron-rich terms do not form gels but strongly emit light between 400 and 600 nm. The charge carrier mobility was also measured by time-of-flight transient photocurrent technique in the mesophases for some of the compounds. They display hole-transport performances with positive charge mobility in the 10 -3 cm -2 V -1 s -1 range, consistent with the high degree of ordering and stability of the columnar superstructures. One mesogen in particular with benzodithiophen-4,8-dione core shows outstanding ambipolar charge carrier transport with both high electron (μe = 6.6×10 -3 cm -2 V -1 s -1 ) and hole (μh = 4.5×10 -3 cm -2 V -1 s -1 ) mobility values.

International audience; The Diels–Alder reaction kinetics between diphenylfulvene and maleimide using mechanochemistry and in liquid state is described. This reaction was carried out in solid state using a modified vibratory ball-mill with temperature control and in solution with toluene as solvent. The effect of temperature, ball mass, material, additives, and aging reaction were studied. We reported for the first time the kinetics of a mechanochemical reaction depending on the ratio ball mass/mass of the reagent. A new kinetic model has been established that corresponds well to our experimental data and allows an estimation of the global activation energy. In solution, the retro Diels–Alder reaction was observed. The reaction was second order for the formation of endo and exo and first order for the retro Diels–Alder reaction. The grinding method shows many advantages compared to solution: shorter reaction time, total reaction, and better selectivity.

International audience; A generic synthetic method based on the Suzuki-Scholl reactions was successfully exploited to yield new poly(hetero)aromatic hydrocarbons containing carbazole, fluorene or fluorenone moieties. These butterfly-like mesogens exhibit columnar mesophases, form fibrous gels in various solvents, emit blue to orange light in films and solutions and show outstanding photocurrent behavior with charge carrier mobility in the ∼0.03 cm 2 V −1 s −1 range.

The design and synthesis of a novel rotaxane/foldaxane hybrid architecture is reported. The winding of an aromatic oligoamide helix host around a dumbbell-shaped thread-like guest, or axle, already surrounded by a macrocycle was evidenced by NMR spectroscopy and X-ray crystallography. The process proved to depend on the position of the macrocycle along the axle and the associated steric hindrance. The macrocycle thus behaves as a switchable shield that modulates the affinity of the helix for the axle. Reciprocally, the foldamer helix acts as a supramolecular auxiliary that compartmentalizes the axle. In some cases, the macrocycle is forced to move along the axle to allow the foldamer to reach its best recognition site.

International audience; The synthesis of molecules bearing (trifluoromethylselenyl)methylchalcogenyl groups is described via an efficient two-step strategy based on a metal-free photoredox catalyzed decarboxylative trifluoromethylselenolation with good yields up to 88% which raised to 98% in flow chemistry conditions. The flow methods allowed also to scale up the reaction. The mechanism of this key reaction was studied. The physico-chemical characterization of these emerging groups was performed by determining their Hansch-Leo lipophilicity parameters with high values up to 2.24. This reaction was also extended to perfluoroalkylselenolation with yields up to 95%. Finally, this method was successfully applied to the functionalization of relevant bioactive molecules such as tocopherol or estrone derivatives.

International audience; Microbiological reductive sulfidation (RS) has rarely been documented, although it represents an efficient strategy for thiol formation. In this work, we reported on the sulfate-respiring bacterium Desulfovibrio sp.86 that has previously demonstrated RS activity toward the pesticide chlordecone. The purpose of the study was to assess its substrate-versatility using a set of 28 carbonyls, to compare with chemical RS and to rationalize the observed trends using a dual experimental and theoretical approach. The chemical RS generally proceeds in two steps (S-O exchange using a sulfur donor like P4S10, reduction of the thione intermediate). Intriguingly, chlordecone was found to be converted into chlordecthiol following the first step. Hence, we designed a protocol and applied it to the 28 substrates to assess their propensity to be directly converted into thiols with the P4S10 treatment alone. Finally, we performed density functional theory calculations on these carbonyls and their thiocarbonyl derivatives to build a set of structural, electronic and thermodynamic parameters. The results showed that chemical and microbiological RS probably involved two distinct mechanisms. Chemically, we observed that several carbonyls, possessing electron-withdrawing groups and/or aromatic rings, were directly transformed into thiols in the presence of P4S10. The correlation obtained with the electron affinity of the thiones led us conclude that a probable single-electron reductive transfer occurred during the first step. We also found that Desulfovibrio sp.86 transformed a variety of aldehydes and ketones, without ever detecting thiones. No significant correlation was observed with the calculated parameters but a relationship between aldehyde RS biotransformation and bacterial growth was observed. Differences in selectivity with chemical RS open the way for further applications in organic synthesis.

International audience; Earlier accounts of triple-decker complexes comprising main group elements and transition metals in the middle-deck, motivated us to synthesize triple-decker complexes containing coinage metals in the middle-deck. As a result, we have explored the reactivity of open-cage nido - [(Cp *M) 2 { mu-B 2 H 2 E 2 }], 1 -3 (Cp * = eta 5 -C 5 Me 5 , 1 : M = Co, E = S ; 2 : M = Co, E = Se; 3 : M = Rh, E = Se) with [CuBr(SMe 2 )]. All the reactions yielded triple-decker complexes, [(Cp *M) 2 { mu-B 2 H 2 E 2 CuBr}], 4 -6 ( 4 : M = Co, E = S ; 5 : M = Co, E = Se; 6 : M = Rh, E = Se) having [CuBr] in the middle-deck. The removal of the SMe 2 ligand resulted in the formation of complexes 4 -6 as a single product. These complexes are examples of triple-decker species having a planar 5-membered [B 2 E 2 Cu] (E = S or Se) middle deck, in which the Cu exists as Cu(I) with an elongated M-Cu bonding interaction. Synthesized complexes have been established by ESI-MS, multinuclear nuclear magnetic resonance (NMR), and IR spectroscopy. The solid-state structures of 5 and 6 were confirmed by single-crystal X-ray diffraction analyses. Density functional theory (DFT) analyses of these complexes have presented a high electron donation from the [B 2 E 2 ] (E = S or Se) fragment of the middle ring to the axial metals and a weak bonding interaction between group 9 metals and Cu.

Antibiotic resistance in bacteria is becoming a major sanitary concern worldwide. The extensive use of large quantities of antibiotics to sustain human activity has led to the rapid acquisition and maintenance of antibiotic resistant genes (ARGs) in bacteria and to their spread into the environment. Eventually, these can be disseminated over long distances by atmospheric transport. Here, we assessed the presence of ARGs in clouds as an indicator of long-distance travel potential of antibiotic resistance in the atmosphere. We hypothesized that a variety of ARGs can reach the altitude of clouds mainly located within the free troposphere. Once incorporated in the atmosphere, they are efficiently transported and their respective concentrations should differ depending on the sources and the geographical origin of the air masses. We deployed high-flow rate impingers and collected twelve clouds between September 2019 and October 2021 at the meteorological station of the puy de Dôme summit (1465 m a.s.l., France). Total airborne bacteria concentration was assessed by flow cytometry, and ARGs subtypes of the main families of antibiotic resistance (quinolone, sulfonamide, tetracycline; glycopeptide, aminoglycoside, β-lactamase, macrolide) including one mobile genetic element (transposase) were quantified by qPCR. Our results indicate the presence of 29 different ARGs' subtypes at concentrations ranging from 1.01 × 10

International audience; A new class of push-pull 1,1,4,4-tetracyanobutadienes (TCBDs) chromophores bearing a γ-pyranylidene as a proaromatic donor group have been developed, characterized and studied for their electrochemical, photophysical and second-order nonlinear optical (NLO) properties. [2 þ 2] Cycloaddition-retroelectrocyclizations (CA-RE) with tetracyanoethylene (TCNE) allowed the formation of new TCBDs by taking advantage of the electron-donating ability of γ-pyranylidene functional groups. The limits of the reaction between TCNE and the corresponding alkynes have been investigated, both in terms of reactivity and solubility. Electrochemical studies of pyranylidene-TCBD 1a-1j revealed two reversible reduction waves typical of TCBDs, and two oxidation waves originating from the γ-pyranylidene moiety. More complex electrochemical signals have been recorded when studying chromophores bearing multiple TCBD and/or γ-pyranylidene units. All pyranylidene-TCBDs showed panchromatic absorption properties, extending to the NIR in some cases. Changes made around the electron-withdrawing TCBD units significantly affected the ICT performance of the push-pull chromophores. Computational studies have been performed on this series of compounds to rationalize the origin of their optical properties. TD-DFT calculations confirmed that the synthesized pyranylidene-TCBDs are potential NLOphores. The second-order NLO properties of all chromophores were determined by the Electric Field-Induced Second Harmonic generation (EFISH) technique, and all systems exhibited valuable NLO properties with large μβ EFISH values for purely organic compounds, up to 5700 10 À48 esu.

A set of new guaianolide derivatives (1–9) was obtained from ludartin, achalensolide, and 11,13-dihydroachalensolide by application of catalytic nitrene transfer reactions. Intermolecular nitrene C(sp3)−H insertions led to the amination of C-1, C-2, and C-10 positions, while alkene aziridination was also observed under these reaction conditions. The antiproliferative activity of natural compounds and their derivatives was evaluated against a panel of human solid tumor cell lines. The results show that an increase in the biological activity was observed following amination at the C-2 position of Ludartin, thereby demonstrating the interest in late-stage C−H amination to improve the bioactivity of natural products. Fil: Castro, Sebastián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Padrón, José M.. Universidad de La Laguna; España Fil: Darses, Benjamin. Université Paris-Saclay; Francia. Universite Grenoble Alpes; Francia Fil: Nicotra, Viviana Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Dauban, Philippe. Université Paris-Saclay; Francia

Starphenes show promising optoelectronic properties. Notably, HOMO–LUMO energy gap presumably decreases with their increasing size, making larger homologues extremely desirable. Unfortunately, with the size, their instability and insolubility also increase, challenging classical synthetic ways. A new method has been developed, enabling synthesis of large starphenes in a quantity sufficient for their full characterisation and further applications., Starphenes are attractive compounds due to their characteristic physicochemical properties that are inherited from acenes, making them interesting compounds for organic electronics and optics. However, the instability and low solubility of larger starphene homologs make their synthesis extremely challenging. Herein, we present a new strategy leading to pristine [16]starphene in preparative scale. Our approach is based on a synthesis of a carbonyl-protected starphene precursor that is thermally converted in a solid-state form to the neat [16]starphene, which is then characterised with a variety of analytical methods, such as 13C CP-MAS NMR, TGA, MS MALDI, UV/Vis and FTIR spectroscopy. Furthermore, high-resolution STM experiments unambiguously confirm its expected structure and reveal a moderate electronic delocalisation between the pentacene arms. Nucleus-independent chemical shifts NICS(1) are also calculated to survey its aromatic character., This research has been funded in parts by foundation EXPERIENTIA, ERDF/ESF “UOCHB MSCA Mobility” (No. CZ.02.2.69/0.0/0.0/17 050/0008490), and has received funding from the EraNET Cofund Initiatives Quan-tERA under the European Union's Horizon 2020 research and innovation programme grant agreement ORQUID. This project has received financial support from the CNRS through the MITI interdisciplinary programs and JST-ERATO (No. JPMJER1903) and JSPS-WPI. Financial support is also acknowledged from the Spanish Ministry of Science and Innovation (MAT2016-78293-C6, PID2019-107338RB-C63), from the Basque Government (IT-1255-19), from the Spanish National Research Council (CSIC, COOPB20432), from the Euro-pean Regional Development Fund (ERDF) under the program Interreg V-A España-Francia-Andorra (contract no. EFA 194/16 TNSI) and from the European Research Council (grant agreement no. 635919). The authors thank Yannick Coppel (LCC-CNRS, Toulouse) for recording CP-MAS spectra, Jean-Francois Meunier (LCC-CNRS, Toulouse) for thermogravimetric analysis and Vladimir Vrkoslav (IOCB-Prague) for recording MS MALDI spectra.

Real-time quantification of reactive nitrogen and oxygen species (ROS) in cells is of paramount importance as they are essential for cellular functions. Their excessive formation contributes to the dysfunction of cells and organisms, ultimately leading to cell death. As ROS are mostly produced in the mitochondria, we have synthesized a fluorescent probe able to reach this organelle to detect and quantify, in real time, the variation of ROS by time-resolved microfluorimetry. The new probes are based on the long fluorescence lifetime of pyrene butyric acid (PBA). Two PBA isomers, attached at their 1- or 2-positions to a peptide vector to target mitochondria, were compared and were shown to allow the measurement of free radical species and oxygen, but not non-radical species such as H2 O2 .

International audience; We describe an efficient photoredox system, relying on decatungstate/disulfide catalysts, for the hydrofunctionalization of styrenes. In this methodology the use of disulfide as co-catalyst was shown to be crucial for the reaction efficiency. This photoredox system was employed for the hydro-carbamoylation,-acylation,-alkylation and-silylation of styrenes, giving access to a large variety of useful building blocks and high-value molecules such as amides and unsymmetrical ketones from simple starting materials.

Metal-catalyzed alkylation of 1,1-dihalovinyl moiety commonly suffers from both a lack of stereoselectivity and the overreaction leading to the dialkylation product. The methodology described herein features a new pathway to alkylate stereoselectively β,β-dichlorostyryl substrates to provide the Z-trisubstituted olefin only with fair to good yields. This cross-coupling reaction bears on the smooth and photoinduced formation of a C-centered radical that engages in a nickel-catalyzed organometallic cycle to form the key Csp2–Csp3 bond.

International audience; Polyazanes (that is, higher nuclearity homologues of hydrazines) with increasing numbers of bound nitrogen atoms (from 3 to 5) were prepared via additions of lower order polyazanes to diazo reagents, including the first pentazane ever described. A structure was obtained. It was shown that the polynitrogen chains adopt a helical conformation. DFT modeling shows that the arrangement subsists in solution. While the polyazanes are all reducing agents, they become less so with the increasing number of nitrogens.

International audience; Porphyrins and N-heterocyclic carbenes (NHCs) are both relevant ligands in the fields of coordination and organometallic chemistry. Despite evident structural differences, porphyrins and NHCs have a lot in common such as their ability to form strong metalligand bonds and their use in catalysis, materials science and biomedicine. During the last decade, several molecular systems combining porphyrins and NHC ligands were reported in the literature. The present review gathers relevant examples where NHC ligands are either axially bonded to metalloporphyrins or covalently attached to the porphyrin cores. Structural diversity, electronic interplay between porphyrins and NHCs and some relevant applications in catalysis and biomedicine are notably described. Finally, molecular systems combining NHCs with other original porphyrinoids such as Nconfused porphyrins, subporphyrins and norcorroles are also presented.

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International audience; We introduce a general and relatively straightforward protocol aimed at determining the absolute photoinduced radical generation efficiency via NMR monitoring. This approach relies on the use of a radical scavenger probe that combines a nitroxide moiety that specifically reacts with radicals and a trifluoromethyl group used as a 19F NMR signaling unit. Using an LED source, whose fluence is precisely determined by a chemical actinometry procedure also described herein, the method is used to determine the radical photogeneration quantum yields of three well-known polymerization initiators: azobisisobutyronitrile (AIBN), 4,4’-bis(N,N-diethylamino)benzophenone (BDEBP, a derivative of Michler’s ethyl ketone), and 2,4,6-trimethylbenzoyl diphenylphosphine oxide (MAPO). The overall good agreement with values previously reported in the literature proves the robustness of this new method. We then extended the study to the precise measurement of the quantum yield of free-radical photogeneration on a newly synthesized photoinitiator used for two-photon direct laser writing. This study highlights the potential of this methodology for the quantitative determination of photoinduced radical generation efficiency used in many fields of applications.

International audience; The improvement of molecular diversity is one of the major concerns of chemists since the continuous development of original synthetic molecules provides unique scaffolds usable in organic and bioorganic chemistry. The challenge is to develop versatile platforms with highly controlled chemical three-dimensional space thanks to controlled chirality and conformational restraints. In this respect, cyclic β-amino acids are of great interest with applications in various fields of chemistry. In addition to their intrinsic biological properties, they are important precursors for the synthesis of new generations of bioactive compounds such as antibiotics, enzyme inhibitors, and antitumor agents. They have also been involved in asymmetric synthesis as efficient organo-catalysts in their free form and as derivatives. Finally, constrained cyclic β-amino acids have been incorporated into oligomers to successfully stabilize original structures in foldamer science with recent successes in health, material science, and catalysis. Over the last ∼10 years, we focused on bicyclic β-amino acids possessing a bicyclo[2.2.2]octane structure. This latter is a structural key element in numerous families of biologically active natural and synthetic products and is an interesting template for asymmetric synthesis. Nonetheless, reported studies on bicyclic carbo-bridged compounds are rather limited compared to those on bicyclic-fused and heterobridged derivatives. In this Account, we particularly focused on the synthesis and applications of the 1-aminobicyclo[2.2.2]octane-2-carboxylic acid, named, ABOC, and its derivatives. This highly constrained bicyclic β-amino acid, with a sterically hindered bridgehead primary amine and an endocyclic chiral center, displays drastically reduced conformational freedom. In addition, its high bulkiness strongly impacts the spatial orientation of the appended functionalities and the conformation of adjacent building blocks. Thus, we have first expanded a fundamental synthetic work by a wide ranging study in the field of foldamers, in the design of various stable peptide/peptidomimetic helical structures incorporating the ABOC residue (11/9-, 18/16-, 12/14/14-, and 12/10-helices). In addition, such bicyclic residue was fully compatible with and stabilized the canonical oligourea helix, whereas very few cyclic β-amino acids have been incorporated into oligoureas. In addition, we have pursued with the synthesis of some ABOC derivatives, in particular the 1,2-diaminobicyclo[2.2.2]octane chiral diamine, named DABO, and its investigation in chiral catalytic systems. Covalent organo-catalysis of the aldol reaction using ABOC-containing tripeptide catalysts provided a range of aldol products with high enantioselectivity. Moreover, the double reductive condensation of DABO with various aldehydes allowed the building of new chiral ligands that proved their efficiency in the copper-catalyzed asymmetric Henry reaction

International audience; Herein, we report an efficient enantioselective cleavage of the acyl-moiety of a set of α-phenyl ethyl esters with different chain-lengths catalyzed by lipase B from Candida antarctica (CAL-B) by comparing two reactional approaches: anhydrous media with sodium carbonates and micro-aqueous medium. The deacylation is performed in organic solvent, in the presence of Na2CO3 in the first case, and by addition of a drop of phosphate buffer solution pH=7 in the second. The results show the high efficiency of the deacylation in the presence of the sodium carbonate for the enzymatic resolution of all the esters and that in term of reactivity (31% ≤ conv ≤ 50%) and selectivity (E >200). While, during the hydrolysis in micro-aqueous media, the conversion is strongly affected by the length of the acyl-chain side, the conversion decreases from conv =50% with the 1-phenylethyl acetate 1a to conv =19% with 1-phenyethyl dodecanoate 6a, and this, even if the selectivity remains high (E>89). In both conditions, the lipase CAL-B shows a high enantioselectivities in favor of (R)-1-phenyl ethanol enantiomer (conv >45%, E>200) but the reactivity is modulated by the form and the size of the acyl-chain side.

International audience; Polyaromatic 7-membered rings featuring main group elements (P, Ge) are described. Coordination complexes were synthesized with the trivalent phosphepines highlighting that these P-heterocycles are promising ligands. Furthermore, those polyaromatic germepines and phosphepines appear as interesting building blocks for optoelectronics.

International audience; The development of ion transport systems employing halogen bonding for function and structure started less than a decade ago. This line of research was motivated by the intrinsically compatible characteristics of this non-covalent interaction with transmembrane ion transport, leading to a number of macrocyclic and supramolecular approaches to be explored and reported. Amidst more elaborated molecular frameworks, simple perfluoro-1-iodoalkanes have conclusively proven the relevance and suitability of halogen bonding towards this functional application. Indeed, the strength and directionality of the halogen bond, added to a hydrophobic scaffold, was sufficient to enable anion binding and transport across a lipid bilayer membrane. Macrocyclic arrays were advanced to demonstrate multitopic binding and transport, further enlarging the possibilities. Finally, ion channels relying on halogen bonding to enable multiion hoping across the membrane have also been reported. These larger structures could be constructed both using covalent and supramolecular approaches and were the most active transporters exploiting halogen bonding.

We demonstrate here a rapid and comfortable synthetic sequence to benzothiadiazinone dioxide (six-membered cyclic sulfamide) derivatives, analogues of Monastrol, which is known to be a specific mitotic kinesin Eg5 inhibitor. Fourteen novel compounds (1d–14d) were synthesized through three component Biginelli reaction, by condensation of aromatic aldehyde, sulfamide, and cyclohexane-1,3-dione. A wide range of substrates is compatible in this reaction, producing excellent yields (82–92%) in short time (5–10 min). The reaction is performed under solvent-free, catalysed by H2SO4/CH3COOH (1/9) using microwave irradiation. The structure of the obtained substances was confirmed by 1H, 13C, HMBC, HSQC NMR spectroscopy, IR spectroscopy, and mass spectrometry, as well as elemental analysis. A single crystal of the (4-phenyl-4,6,7,8-tetrahydro-1H benzo[c][1,2,6]thiadiazin-5(3H)-one 2,2-dioxide has been obtained after recrystallization in ethanol/acetone (9/1) and selected for X-ray study.

International audience; Highly enantio- and regioselective (3 + 2) formal cycloaddition of β-substituted ene- and thioenecarbamates as well as cyclic enamides with quinone diimides catalyzed by a BINOL- and SPINOL-derived phosphoric acid is reported. A wide variety of 2,3-disubstituted 2-aminoindolines, including polycyclic ones, were prepared in generally high yields (up to 98%) with moderate to complete diastereoselectivities and in most cases excellent enantioselectivities (up to 99% ee).

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Birds ingest ethanol when farmers feed it to treat mild respiratory infections and to improve the feed conversion ratio (FCR) or when birds are exposed to ethanol as avian models in alcohol-related...

In the past few years, several drugs derived from nucleic acids have been approved for commercialization and many more are in clinical trials. The sensitivity of these molecules to nuclease digestion in vivo implies the need to exploit resistant non-natural nucleotides. Among all the possible modifications, the one concerning the internucleoside linkage is of particular interest. Indeed minor changes to the natural phosphodiester may result in major modifications of the physico-chemical properties of nucleic acids. As this linkage is a key element of nucleic acids’ chemical structures, its alteration can strongly modulate the plasma stability, binding properties, solubility, cell penetration and ultimately biological activity of nucleic acids. Over the past few decades, many research groups have provided knowledge about non-natural internucleoside linkage properties and participated in building biologically active nucleic acid derivatives. The recent renewing interest in nucleic acids as drugs, demonstrated by the emergence of new antisense, siRNA, aptamer and cyclic dinucleotide molecules, justifies the review of all these studies in order to provide new perspectives in this field. Thus, in this review we aim at providing the reader insights into modified internucleoside linkages that have been described over the years whose impact on annealing properties and resistance to nucleases have been evaluated in order to assess their potential for biological applications. The syntheses of modified nucleotides as well as the protocols developed for their incorporation within oligonucleotides are described. Given the intended biological applications, the modifications described in the literature that have not been tested for their resistance to nucleases are not reported., This review covers comprehensively the chemical synthesis and hybridization properties of modified internucleoside linkages with reported nuclease resistances and discusses their assets for potential biological applications.

International audience; Oxidation of organic substrates is achieved in nature under mild conditions thanks to metalloenzymes but remains a challenge for chemists. Herein we show by UV-Vis spectroelectrochemistry that when MnIIITPPCl is electrochemically reduced to MnII in CH2Cl2 under O2, a MnIIO2˙ species is generated. Benzoic anhydride reacts with the latter triggering a catalytic current in cyclic voltammetry. Electrolysis on the catalytic wave in the presence of cyclooctene leads to its oxygenation or halogenation depending on the axial ligand present as reported here for the first time.

The first example of diamino-benzoquinonediimine bearing both electron-donating and electron-withdrawing groups on the same 6-π electron subunit was synthesized using a straightforward one pot strategy. Photophysical analysis and theoretical calculations demonstrate that this unique substitution pattern is efficient to favour the establishment of a single tautomeric structure in solution.