Search

International audience; Polymerization photoinitiators that can be activated under low light intensity and in the visible range are being pursued by both the academic and industrial communities. To efficiently harvest light and initiate a polymerization process, dyes with high molar extinction coefficients in the visible range are ideal candidates. In this field, Donor-acceptor Stenhouse Adducts (DASA) which belong to a class of recently discovered organic photochromic molecules still lack practical applications. In this work, a series of DASA-based dyes are proposed as photoinitiators for the free radical polymerization of (meth)acrylates upon exposure to a near infrared light (laser diode at 785 nm).

The design of photoinitiators activable under low-light intensity is an active research field, supported by the recent energetic sobriety plans imposed by numerous countries in Europe. With an aim to simplify the composition of the photocurable resins, Type I photoinitiators are actively researched as these structures can act as monocomponent systems. In this field, a family of structures has been under-investigated at present, namely, glyoxylates. Besides, the different works carried out in three years have evidenced that glyoxylates and related structures can be versatile for the design of Type I photoinitiators. In this review, an overview of the different glyoxylates and related structures reported to date is provided.

International audience; Photopolymerization is an active research field and recently, a great deal of efforts has been devoted to replace the energy-consuming UV irradiation setups by the popular and easily available energy-saving light-emitting diodes (LEDs). With aim at going a step further, sunlight can be used as an inexpensive and unlimited light source to perform polymerization processes. In this case, no energy is required anymore, and the use of photopolymerization for various outdoor applications becomes possible. Over the years, and with aim developing reliable photoinitiating systems, various dyes have been developed, enabling in the case of sunny days to efficiently promote polymerization processes. In this review, an overview on the different photoinitiating systems developed for polymerization processes done under sunlight or even daylight is provided. Polymerization efficiency is often compared to that obtained with artificial light sources, enabling to determine the efficacy of the photoinitiating systems under sunlight.

International audience; Electronic states with partial or complete doubly excited character play a crucial role in many areas, such as singlet fission and non-linear optical spectroscopy. Although doubly excited states have been studied in polyenes and related systems for many years, the assignment as singly vs. doubly excited, even in the simplest case of butadiene, has sparked controversies. So far, no well-defined framework for classifying doubly excited states has been developed, and even more, there is not even a well-accepted definition of doubly excited character as such. Here, we present a solution: a physically motivated definition of doubly excited character based on operator expectation values and density matrices, which works independently of the underlying orbital representation, avoiding ambiguities that have plagued earlier studies. Furthermore, we propose a classification scheme to differentiate three cases: (i) two single excitations occurring within two independent pairs of orbitals leaving four open shells (D OS), (ii) the promotion of both electrons to the same orbital, producing a closed-shell determinant (D CS), and (iii) a mixture of singly and doubly excited configurations not aligning with either one of the previous cases (D mix). We highlight their differences in underlying energy terms and explain their signatures in practical computations. The three cases are illustrated through various high-level computational methods using dimers for D OS , polyenes for D mix , and cyclobutane and tetrazine for D CS. The conversion between D OS and D CS is investigated using a well-known photochemical reaction, the photodimerization of ethylene. This work provides a deeper understanding of doubly excited states and may guide more rigorous discussions toward improving their computational description while also giving insight into their fundamental photophysics.

International audience; The supramolecular self-assembly of s-indacene-1,3,5,7(2H,6H)-tetrone on the Cu(111) surface was investigated under ultrahigh vacuum by room-temperature scanning tunneling microscopy supported by theoretical modelling based on density functional theory. In total, six different phases were found, driven by hydrogen bonding, metal ligand coordination or covalent coupling. Host–guest interactions allowed for the accommodation of molecular or metal clusters inside the open nanoporous patterns. In one phase, molecular trapping was stochastically observed inside the large periodic nanopores created inside the supramolecular network. The three metal–organic networks observed resulted in the creation of different kinds of regular arrays of isolated metal adatoms or adatom clusters with a lattice period larger than 1 nm.

International audience; Dynamic Nuclear Polarization has recently emerged as a tool to enhance the sensitivity of solid-state NMR experiments. However, so far high enhancements (>100) are limited to relatively low magnetic fields, and DNP at fields higher than 9.4 T significantly drops in efficiency. Here we report solid-state Overhauser effect DNP enhancements of over 100 at 18.8 T. This is achieved through the unexpected discovery that enhancements increase rapidly with increasing magic angle spinning rates. The measurements are made using 1,3-bisdiphenylene-2-phenylallyl (BDPA) dissolved in ortho-terphenyl (OTP) at 40 kHz MAS. We introduce a source-sink diffusion model for polarization transfer which is capable of explaining the experimental observations. The advantage of this approach is demonstrated on mesoporous alumina with the acquisition of well-resolved DNP surface enhanced 27Al CP spectra.

International audience; Recent amazing results (Nkolo et al., Org. Biomol. Chem., 2017, 6167) on the effect of solvents and polarity on the C-ON bond homolysis rate constants kd of alkoxyamine R1R2NOR3 led us to re-investigate the antagonistic effect of intramolecular hydrogen-bonding (IHB) on kd. Here, IHB is investigated both in the nitroxyl fragment R1R2NO and in the alkyl fragment R-3, as well as between fragments, that is, the donating group on the alkyl fragment and the accepting group on the nitroxyl fragment, and conversely. It appears that IHB between fragments (inter IHB) strikingly decreases the homolysis rate constant kd, whereas IHB within the fragment (intra IHB) moderately increases kd. For one alkoxyamine, the simultaneous occurrence of IHB within the nitroxyl fragment and between fragments is reported. The protonation effect is weaker in the presence than in the absence of IHB. A moderate solvent effect is also observed.

International audience; Dual initiators for controlled radical/ionic polymerization reactions attract much attention in terms of preparation of new materials. We studied the potential of dual-initiator alkoxyamines 3 [based both on para-substituted aromatic ring for external triggering or initiation of orthogonal polymerization and on N-tert-butyl-N-(1-diethylphosphono-2,2-dimethylpropyl) nitroxide (SG1)] for nitroxide-mediated polymerization (NMP) with various monomers such as styrene, styrene sulphonate, 2-vinyl pyridine or methylmethacrylate. Alkoxyamines 3 were found to be as efficient in the NMP process as N-(2-methylpropyl)-N-(1-diethylphosphono-2,2-dimethylpropyl)-O-(2-carboxylprop-2-yl)hydroxylamine (1). Furthermore, in sharp contrast to 1, alkoxyamines 3 were easier to functionalize.

International audience; The synthesis of degradable vinyl polymer nanoparticles/latexes in aqueous dispersed media is receiving much attention, particularly for biomedical applications and plastic pollution control, as it can circumvent the severe limitations associated with the emulsification of preformed degradable polymers. Polymerization-induced self-assembly (PISA), which enables the in situ formation of aqueous suspensions of diblock copolymer nano-objects of high solids content, has become a very popular polymerization process due to its many advantages in terms of simplicity, robustness, scalability, and versatility. However, the preparation of degradable vinyl polymer nanoparticles by direct aqueous PISA has never been reported. This severely limits the use of PISA in biomedical and environmental applications. Herein, we report the first aqueous emulsion PISA able to generate degradable vinyl polymer nanoparticles. It relies on radical ring-opening polymerization-induced self-assembly (rROPISA) of traditional vinyl monomers (n-butyl acrylate or styrene) with dibenzo[c,e]oxepane-5-thione (DOT), a thionolactone that features high stability in protic solvents and favorable reactivity with many vinyl monomers and is a precursor of labile thioester groups in the main chain. Stable aqueous suspensions of thioester-containing diblock copolymer nanoparticles were obtained with both vinyl monomers. Extensive degradation of the copolymers and the nanoparticles was successfully demonstrated under aminolytic or basic conditions. Given the success of the PISA process within the polymer community, this work has the potential to greatly expand its use in many areas, from nanomedicine (providing applicability to biocompatible vinyl polymers) to degradable coatings and sustained materials.

International audience; X-ray and electron-beam (E-beam) sterilization technologies were assessed to supplement gamma sterilization, the most common radiation technology used today for biopharmaceutical product sterilization. The mechanical properties of a PE/EVOH/PE film were studied using tensile tests and dynamical mechanical analysis after each irradiation technology (i.e., gamma, electron beam and X-ray irradiations). The effects of each irradiation were compared using two statistical methods. The results indicate that the three irradiation technologies induce no difference in mechanical properties in the investigated dose range for this material.

International audience; The design of photoinitiating systems activable in the visible range and under low light intensity is an active research field supported by the vast applications of photopolymerization. In the search for new dyes that can exhibit panchromatic absorptions, anthraquinone has been identified as a promising scaffold. Over the years, numerous modifications have been carried out on this scaffold by molecular engineering, enabling to design water-soluble, panchromatic or photobleachable dyes. In this review, an overview of the recent advances concerning photopolymerization with anthraquinone-based photoinitiating systems is given.

International audience; The determination of the chemical nature of the organic matter associated with phytoliths remains a challenge. This difficulty mainly stems from amounts of organic carbon (C) that are often well below the detection limit of traditional spectroscopic tools. Conventional solid-state 13 C Nuclear Magnetic Resonance (NMR) is widely used to examine the nature and structure of organic molecules, but its inherent low sensitivity prohibits the observation of diluted samples. The recent advent of commercial microwave source in the terahertz range triggered a renewed interest in the Dynamic Nuclear Polarization (DNP) technique to improve the signal to noise ratio of solid-state NMR experiments. With this technique, the 13 C spectrum of a phytolith sample containing 0.1% w/w C was obtained overnight with sufficient quality to permit a semi-quantitative analysis of the organic matter, showing the presence of peptides and carbohydrates as predominant compounds. Considering the natural abundance of the 13 C isotope, this experiment demonstrates that DNP NMR is sufficiently sensitive to observe spin systems present in amounts as low as a few tens of ppm. The molecular analysis of natural organic matter in organisms, soils or sediments is a challenging field for our understanding of the processes involved in the carbon cycle. Among the many challenges to be met is the difficulty in obtaining a quantitative or semi-quantitative speciation of the organic carbon, with the least possible preparation steps. Indeed, several chemical steps are often required to purify the molecular compounds to be analyzed , from the minerals they are associated with 1-3. Unfortunately these steps can modify the molecular nature of the compounds to be analyzed, especially when HF is involved 4. In this context, 13 C Nuclear Magnetic Resonance (NMR), is an attractive method since it is element specific and therefore does not necessarily require prior extraction of the organic C, as long as the mineral matrix is free from paramagnetic elements (e.g. Fe(II), Fe(III), Cu(II), etc.) which cause substantial signal loss by broadening the lines beyond detection 5-7. Furthermore, 13 C NMR provides a detailed analysis of the nature of the organic C from its surrounding matrix, and the quantitative exploitation can be easily performed using an internal or external reference, or without calibration when only relative proportions are needed. This technique has been successfully used to investigate plant tissuese.g 8. and transformation of organic matter in soils e.g. refs 9-11. In this context, 13 C NMR analysis of organics associated with biogenic silica is a favorable case. In higher plants, silicon is acquired by roots from soils and precipitated in or between the cells as micrometric hydrous amorphous biosilica particles called phytoliths. Phytolith abundances range from

Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway., B.R. and L.I. thank the Regional Council of Franche-Comté (France) for financial support, and M.-J. Henriot (PHV Pharma) for support in the HPLC analyses. M.B. thanks the Regional Council of Franche-Comté(France) for a Ph.D. grant. J.E. has a grant from ISCIII (Programa Miguel Servet, CP14/00008). D.J., J.J., V.S., and O.S. thank Jitka Pichova for a skillful technical assistance. This work was supported by the project MH CZ-DRO (UHHK, 00179906) and by Long Term Development Plan-1011 of Faculty of Military Health Sciences, University of Defence (Czech Republic). R.L. thanks ISCIII (Programa Miguel Servet, CP11/00165; grant PI14/00372), Bayer AG “From targets to novel drugs” (grant 2015-03-1282) and Fundación FIPSE (grant 12-00001344-15). P.M. thanks MECD for a FPU fellowship (FPU13/03737).

International audience; We report herein the first example of a SNAr reaction using TDAE-initiated carbanions in quinazoline series. The o-nitrobenzyl carbanion, formed by the action of TDAE on o-nitrobenzyl chloride, reacts with 4-chloro-2-trihalomethylquinazolines 4 and 5 via a SNAr mechanism. This enabled a new series of 4-benzyl-2-trihaloquinazoline derivatives to be synthesized in good yields under mild reaction conditions offering promising prospects for pharmacomodulation. (C) 2011 Elsevier Ltd. All rights reserved.

International audience; Recent applications of bi-, oligo-or polyradicals to spin sciences have generated considerable interest in the design of new bi/oligoradical organic molecules. Nevertheless, studies of physicochemical properties open shell systems are generally based on stable homonuclear organic radicals, which represent only a small portion of the existing radicals. In this context, diazene precursors of heteroatomic radicals were incorporated into the 2 SBA-15 silica framework. Photolysis at 360 nm of the diazene moiety resulted in the formation of two face-to-face oxygen-and sulfur-centered radicals. These systems were characterized by X-, Q-and W-band EPR spectroscopy by comparing them to silicas functionalized with either face-to-face sulfur-centered radicals or face-to-face oxygencentered radicals. These EPR studies allowed measuring their half-life as well as their relaxation times (T1 and T2). The properties of silicas functionalized with sulfur-and oxygen-centered radicals fall between those measured for the two reference systems functionalized with only sulfur-or oxygen-centered radicals. These nanostructured silicas functionalized by two radicals of different nature are new potential candidates as polarizing agent for DNP NMR.

The combination of nuclear and electron magnetic resonance techniques, in pulse and continuous wave regimes, is used to unravel the nature and features of the light-induced magnetic state arising at the surface of chemically prepared zinc oxide nanoparticles (NPs) occurring under 120 K when subjected to a sub-bandgap (405 nm) laser excitation. It is shown that the four-line structure observed around g ∼ 2.00 in the as-grown samples (beside the usual core-defect signal at g ∼ 1.96) arises from surface-located methyl radicals (•CH3), originating from the acetate capped ZnO molecules. By functionalizing the as-grown zinc oxide NPs with deuterated sodium acetate, the •CH3 electron paramagnetic resonance (EPR) signal is replaced by trideuteromethyl (•CD3). For •CH3, •CD3, and core-defect signals, an electron spin echo is detected below ∼100 K, allowing for the spin–lattice and spin–spin relaxation-time measurements for each of them. Advanced pulse-EPR techniques reveal the proton or deuteron spin-echo modulation for both radicals and give access to small unresolved superhyperfine couplings between adjacent •CH3. In addition, electron double resonance techniques show that some correlations exist between the different EPR transitions of •CH3. These correlations are discussed as possibly arising from cross-relaxation phenomena between different rotational states of radicals.

Low sensitivity is the primary limitation to extending nuclear magnetic resonance (NMR) techniques to more advanced chemical and structural studies. Photochemically induced dynamic nuclear polarization (photo-CIDNP) is an NMR hyperpolarization technique where light is used to excite a suitable donor–acceptor system, creating a spin-correlated radical pair whose evolution drives nuclear hy-perpolarization. Systems that exhibit photo-CIDNP in solids are not common and this effect has, up to now, only been observed for 13C and 15N nuclei. However, the low gyromagnetic ratio and natural abundance of these nuclei trap the local hyperpolarization in the vicinity of the chromophore and limit the utility for bulk hyperpolarization. Here we report the first example of optically enhanced solid-state 1H NMR spectroscopy in the high-field regime. This is achieved via photo-CIDNP of a donor–chromophore–acceptor molecule in a frozen solution at 0.3 T and 85 K, where spontaneous spin diffusion among the abundant strongly coupled 1H nuclei relays polarization through the whole sample, yielding a 16-fold bulk 1H signal enhancement under continuous laser irradiation at 450 nm. These findings enable a new strategy for hyperpolarized NMR beyond the current limits of conventional microwave-driven DNP.

International audience; Mitochondria, an essential organelle involved in cellular respiration, energy production, and cell death, is the main cellular source of reactive oxygen species (ROS), including superoxide. Mitochondrial diseases resulting from uncontrolled/excess ROS generation are an emerging public health concern and there is current interest for specific mitochondriotropic probes to get information on in situ ROS production. As such, nitrones vectorized by the triphenylphosphonium (TPP) cation have recently drawn attention despite reported cytotoxicity. Herein, we describe the synthesis of 13 low-toxic derivatives of N-benzylidene-1-diethoxyphosphoryl-1-methylethylamine N-oxide (PPN) alkyl chain-grafted to a pyridinium, triethylammonium or berberinium lipophilic cation. These nitrones showed in vitro superoxide quenching activity and EPR/spin-trapping efficiency towards biologically relevant free radicals, including superoxide and hydroxyl radicals. Their mitochondrial penetration was confirmed by 31P NMR and anti-apoptotic properties assessed inhydrogen peroxide treated Schwann cells. Two pyridinium substituted PPNs were identified as potentially better alternatives to TPP nitrones conjugates for studies of mitochondrial oxidative damage.

An active environment is any atomic or molecular system changing a chromophore's nonadiabatic dynamics compared to the isolated molecule. The action of the environment on the chromophore occurs by changing the potential energy landscape and triggering new energy and charge flows unavailable in the vacuum. Surface hopping is a mixed quantum-classical approach whose extreme flexibility has made it the primary platform for implementing novel methodologies to investigate the nonadiabatic dynamics of a chromophore in active environments. This Perspective paper surveys the latest developments in the field, focusing on charge and energy transfer processes. ispartof: PHYSICAL CHEMISTRY CHEMICAL PHYSICS vol:25 issue:12 pages:8293-8316 ispartof: location:England status: published

International audience

International audience; Visible light photopolymerization has extensively been studied during the last decades since alternatives to UV processes have to be found rapidly. Indeed, based on the Minamata Convention, Hg irradiation setups must be suppressed from industrial applications. Even if the use of visible light is beneficial in terms of depth of cure and safety for the manipulator, photopolymerization in water is still far aside to the other polymerization processes. At present, only few visible light photoinitiators are soluble in water, speeding down the development of greener polymerization processes. In this review, an overview of the recent advances on water-soluble photoinitiating systems is provided. Even if water-solubility is a key parameter to polymerize in water, the monomer conversion that can be achieved is also important. For these reasons, comparisons with reference photoinitiating systems soluble in water is provided.

As part of our ongoing scaffold-hopping work on an antikinetoplastid 3-nitroimidazo[1,2-a]pyridine scaffold, we explored 3-nitroimidazo[1,2-b]pyridazine as a potential new antikinetoplastid series. Using conditions previously described by our lab, we obtained 6-chloro-3-nitro-2-[(phenylsulfonyl)methyl]imidazo[1,2-b]pyridazine with 54% yield. In vitro activity of this compound was evaluated against both the promastigote form of Leishmania donovani, the axenic amastigote form of Leishmania infantum and the trypomastigote blood stream form of Trypanosomabrucei brucei, and its influence on cell viability was assessed on the HepG2 cell line. However, despite good activity against the trypomastigote blood stream form of T. b. brucei (EC50 = 0.38 µM), it showed poor solubility in both HepG2 (CC50 > 7.8 µM) and L. infantum axenic amastigotes (EC50 > 1.6 µM) culture media, associated with a loss of activity against the promastigote form of L. infantum (EC50 > 15.6 µM).

International audience; From a circular plastic economy perspective, a new configuration of Metal Acetylacetonate Bidentate Ligand Interaction (MABLI) mechanism adapted to the chemistry of the recyclable Elium® thermoplastic resins has been recently discovered to initiate the free radical polymerization of these resins under mild conditions (under air, at room temperature, non-purified monomers, absence of hazardous chemical substances). This initiating strategy is based on the synergy between the initial MABLI couple and a phosphine oxide (Type I photoinitiator). Despite the absence of irradiation, the mere presence of the phosphine oxide reduced significantly the curing time and the final conversion obtained is nearly 100%. In order to dismantle the role of each component and to predict new highperformance MABLI redox initiating systems based on a similar configuration, a mechanistic study was pursued. It has resulted in the identification of new hybrid complexes obtained by ligand exchange between the photoinitiator and the metallic complex. On the other hand, presence of the Type I photoinitiator can level up the initiating strategy by combining MABLI and photoactivation into a dual cure approach: thereby, the photolysis yield and the polymerization efficiency of the complexed form of the phosphine oxide was studied and compared to the free form of the photoinitiator.

International audience; An antileishmanial pharmacomodulation at position 4 of 8-nitroquinolin-2(1H)-one was conducted by using the Sonogashira and Suzuki-Miyaura coupling reactions. A series of 25 derivatives was tested in vitro on the promastigote stage of Leishmania donovani along with an in vitro cytotoxicity evaluation on the human HepG2 cell line. Only the derivatives bearing a phenyl moiety at position 4 of the quinoline ring displayed interesting biologic profile, when the phenyl moiety was substituted at the para position by a Br or Cl atom, or by a CF3 group. Among them, molecules 17 and 19 were the most selective and were then tested in vitro on the intracellular amastigote stage of both L. donovani and Leishmania infantum, in parallel with complementary in vitro cytotoxicity assays on the macrophage cell lines THP-1 and J774A.1. Molecule 19 showed no activity on the amastigote stages of the parasites and some cytotoxicity on the J774A.1 cell line while molecule 17, less cytotoxic than 19, showed anti-amastigote activity in L. infantum, being 3 times less active than miltefosine but more active and selective than pentamidine. Nevertheless, hit-molecule 17 did not appear as selective as the parent compound. (C) 2015 Elsevier Ltd. All rights reserved.

International audience; From a recently identified antileishmanial pharmacophore, a structure activity relationship study was conducted by introducing various aminated, phenoxy or thiophenoxy moieties at position 4 of the 8-nitroquinolin-2(1H)-one scaffold, using SNAr reactions. Thus a series of 47 derivatives was synthesized and evaluated in vitro on the promastigote stage of Leishmania donovani. In parallel, the cytotoxicity of the active molecules was tested on the human HepG2 cell line. The results we obtained showed that the introduction of a substituent at position 4 of the antileishmanial pharmacophore can either lead to inactive or active derivatives, depending on the nature of the substituent. Aminated moieties appear as very unfavorable toward antileishmanial activity, while phenoxy or thiophenoxy moieties were shown to maintain the in vitro antileishmanial profile, especially when the phenyl ring of these moieties was substituted at the para or ortho position by a halogen atom (except fluorine), a trifluoromethyl group or a methyl group. Most of these derivatives showed a lack of solubility in the culture media which hindered the in vitro determination of both their cytotoxicity and activity against the intracellular amastigoste stage of L. donovani. (C) 2014 Elsevier Masson SAS. All rights reserved.

International audience; Among carbon-based materials, fullerenes have emerged as very fascinating nanocarbons on account of the interesting properties and applications of some of their derivatives in medicine or materials chemistry. The low solubility of C 60 , the most famous family member, has limited its use in medicinal chemistry but its covalent functionalization with different moieties such as porphyrins or other bioactive molecules changes its physicochemical properties, such as its solubility and biocompatibility. New hybrid compounds, bearing fullerene and steroid units in the same molecule can be regarded as promising functional chimeras with encouraging biomedical applications and have become a topic of considerable interest in the last few years. Recent developments in the syntheses of steroid-fullerene hybrids are described herein.

Numerous new emerging therapies, including oral targeted chemotherapies, have recently entered the therapeutic arsenal against acute myeloid leukemia (AML). The significant shift toward the use of these novel therapeutics, administered either alone or in combination with intensive or low-intensity chemotherapy, changes the prospects for the control of this disease, especially for elderly patients. Glasdegib, an oral Hedgehog pathway inhibitor, showed satisfactory response rates associated with moderate toxicity and less early mortality than standard induction regimens in this population. It was approved in November 2018 by the FDA and in June 2020 by the EMA for use in combination with low-dose cytarabine as a treatment of newly-diagnosed AML in patients aged ≥ 75 and/or unfit for intensive induction chemotherapy. The current paper proposes an extensive, up-to-date review of the preclinical and clinical development of glasdegib. Elements of its routine clinical use and the landscape of ongoing clinical trials are also stated.

International audience; PurposeTo identify T1D-filtering methods, which can specifically isolate various ranges of T1D components as they may be sensitive to different microstructural properties.MethodsModified Bloch-Provotorov equations describing a bi-T1D component biophysical model were used to simulate the inhomogeneous magnetization transfer (ihMT) signal from ihMTRAGE sequences at high RF power and low duty-cycle with different switching time values for the dual saturation experiment: Δt = 0.0, 0.8, 1.6, and 3.2 ms. Simulations were compared with experimental signals on the brain gray and white matter tissues of healthy mice at 7T.ResultsThe lengthening of Δt created ihMT high-pass T1D-filters, which efficiently eliminated the signal from T1D components shorter than 1 ms, while partially attenuating that of longer components (≥ 1 ms). Subtraction of ihMTR images obtained with Δt = 0.0 ms and Δt = 0.8 ms generated a new ihMT band-pass T1D-filter isolating short-T1D components in the 100-µs to 1-ms range. Simulated ihMTR values in central nervous system tissues were confirmed experimentally.ConclusionLong- and short-T1D components were successfully isolated with high RF power and low duty-cycle ihMT filters in the healthy mouse brain. Future studies should investigate the various T1D-range microstructural correlations in in vivo tissues.

International audience; The adaptability of hydrogels allows these structures to be used in a variety of industries, including biomedicine, soft electronics, and sensors.

International audience; On-surface synthesis has provided exciting concepts for the building of covalently bonded molecular nanostructures as well as the exploration of new synthetic pathway alternatives to chemical synthesis in solution. The surface-supported reaction of precursor molecules can result in the formation of 2D molecular networks as well as novel 0D molecular structures. In this study, we investigate in ultrahigh vacuum by low-temperature scanning tunneling microscopy the adsorption of the chiral molecule (R)-6-bromo-3-phenyl-2,3-dihydro-1H-inden-1-one (BrPhINDO) on the Cu(111) surface. Annealing an as-deposited layer of molecules allows to activate two kinds of homocoupling reactions, the Ullmann-like coupling and the Knoevenagel reaction, resulting in the formation of various low-dimensional structures. By studying their prochirality and comparing with the products obtained with the enantiomer precursor, we demonstrate adsorption-induced chiral inversion inducing partial racemization.

International audience; First row transition metal complexes with d 4 to d 7 electronic configuration exhibit spin-crossover (SCO), which can be induced by external stimulus such as temperature, pressure, light. The low-spin to high-spin transition has been largely studied, but very little is known about the reverse process. Here, we present a theoretical study of thermal and light-induced high-to-low spin crossover in prototypical Fe(II) complexes. The lifetime of the high-spin state in the thermal process is determined using Fermi's golden rule. With this methodology, we have accurately computed the transfer rate of the HS state thermal relaxation at several time scales (from sub-nanosecond to a few seconds) in two different iron complexes. The use of quasi-degenerate perturbation theory (QDPT2) in the analysis of the LS-HS spin-orbit coupling have allowed to identify 3T1 as the main intermediate state coupling LS and HS states. The light-induced process has been studied using wavepacket quantum dynamics along the main vibrational coordinates (one symmetric and two asymmetric Fe-N stretchings). The study suggests that after the initial excitation from 5T2g to 5Eg state, the population is transferred back to a vibrationally hot 5 T 2g from which a small amount of population is transferred to the 1A1g via the intermediate 3 T 1g. Most of the population remains trapped in the HS state at the time scale of the simulation. Spin-crossover (SCO) is a molecular phenomena wherein the spin state of the system changes because of an external stimulus such as pressure, temperature, light irradiation or the influence of a magnetic field. This process commonly takes place from the diamagnetic thermally stable low-spin state to the paramagnetic

International audience; We propose a novel approach for an indirect probing of conjugation and hyperconjugation in coreexcited molecules using resonant Auger spectroscopy. Our work demonstrates that the changes in the electronic structure of thiophene (C 4 H 4 S) and thiazole (C 3 H 3 NS), occurring in the process of resonant sulfur K-shell excitation and Auger decay, affect the stabilisation energy resulting from π−conjugation and hyperconjugation. The variations in the stabilisation energy manifest themselves in the resonant S KL 2,3 L 2,3 Auger spectra of thiophene and thiazole. The comparison of the results obtained for the conjugated molecules and for thiolane (C 4 H 8 S), the saturated analogue of thiophene, has been performed. The experimental observations are interpreted using high-level quantum-mechanical calculations and the natural bond orbital analysis.

Dynamic nuclear polarization (DNP) at cryogenic temperatures has proved to be a valuable technique to enhance the sensitivity of solid-state NMR spectroscopy. Over the years, sample formulations have been optimized for experiments at cryogenic temperatures. At 9.4 T, the best performing polarizing agents are dinitroxides such as AMUPol and TEKPol that lead to enhancement factors of around 250 at 100 K. However, the performance of these radicals plummets at higher temperatures. Here we introduce trehalose-based DNP polarizing matrices, suitable to embed biomolecular assemblies. Several formulation protocols are investigated, in combination with various polarizing agents, including a new biradical structure chemically tethered to a trehalose molecule. The DNP efficiency of these new polarizing media is screened as a function of the radical concentration, the hydration level of the matrix and the protein content. Sizeable enhancement factors are reported at 100 K and 9.4 T. More importantly, we show that the DNP performance of these new polarizing media outperform the conventionally used water/glycerol mixture at temperatures above 180 K. This study establishes trehalose matrices as a promising DNP medium for experiments at temperatures >150 K where conventional water-based formulations soften and are no longer viable, thus opening new avenues for DNP enhanced solid-state NMR spectroscopy at temperatures close to ambient temperature.

International audience; In this work, a series of Type I photoinitiators (PIs) based on the naphthoquinone scaffold were designed and synthesized for the first time, in order to induce photopolymerization under visible light. As a result, these PIs exhibit excellent photoinitiation abilities in the presence of acrylates monomers upon LED@405 or @455 nm irradiation. Interestingly, some compounds have better photoinitiation performance than the benchmark Type I phosphine-oxide i.e. diphenyl(2,4,6trimethylbenzoyl)phosphine oxide (TPO) upon exposure to LED@455 nm. Chemical mechanisms supporting the photopolymerization process were investigated through different techniques as well as theoretical calculations. In addition, the new proposed structures were also investigated in two-component photoinitiating systems and exhibited a higher efficiency in free radical photopolymerization. Finally, direct laser write approach is successfully used to fabricate 3D objects.

International audience; Barium stannate titanate (BaTi0.89Sn0.11O3, BTS11) is one of the reported lead-free materials that exhibit high dielectric and piezoelectric properties near ambient temperature. In this work, BTS11 powders were elaborated via a soft chemistry method at very low temperatures using two synthesized approaches combining sol-gel and hydrothermal processes. In the first approach, the effect of the barium precursor on the purity and the crystallinity of the BTS11 powders were studied. In contrast, in the second approach, the influence of the hydrothermal temperature on the BTS11 proprieties was analyzed. As a result, pure and uniform fine powders were obtained at 180 °C. The appropriate mass fraction of BTS11, which leads to high suspension stability in water, is below 3%. These eco-friendly and pure piezoelectric powders can be used without further heat-treatment in several applications such as lead-free piezoelectric decontamination of organic pollutants and photocatalyst, hydrogen generation and as fillers in flexible nanocomposites nano-generators for energy harvesting and energy storage.

International audience; Boronate-based compounds have been used in brain cancer therapy, either as prodrugs or in combination with other modalities. Boronates containing pro-luminescent and fluorescent probes have been used in mouse models of cancer. In this study, we synthesized and developed polyphenolic boronates and mitochondria-targeted polyphenolic phytochemicals (e.g., magnolol [MGN] and honokiol [HNK]) and tested their antiproliferative effects in brain cancer cells. Results show that mitochondria-targeted (Mito) polyphenolic boronates (Mito-MGN-B and Mito-HNK-B) were slightly more potent than Mito-MGN and Mito-HNK in inhibiting proliferation of the U87MG cell line. Similar proliferation results also were observed in other cancer cell lines, such as MiaPaCa-2, A549 and UACC-62. Independent in vitro experiments indicated that reactive nitrogen species (e.g., peroxynitrite) and reactive oxygen species (e.g., hydrogen peroxide) stoichiometrically react with polyphenolic boronates and Mito-polphenolic boronates, forming polyphenols and Mito-polyphenols as major products. Previous reports suggest that both Mito-MGN and Mito-HNK activate cytotoxic T cells and inhibit immunosuppressive immune cells. We propose that Mito-polyphenolic boronate-based prodrugs may be used to inhibit tumor proliferation and mitigate oxidant formation in the tumor microenvironment, thereby generating Mito-polyphenols in situ, as well as showing activity in the tumor microenvironment.

International audience; Photopolymerization under visible light has known major breakthroughs in recent years due to the development of new irradiation setups based on Light-Emitting Diodes (LEDs) enabling now to polymerize resins with low light intensities but also by the urgent need to develop efficient photoinitiating systems perfectly fitting the light sources currently under use in 3D printers. If the use of visible light is the key parameter to increase the thickness of the polymerized films, visible light photoinitiators are also strongly colored compounds that can adversely impact the future use of photopolymers for daily applications. Indeed, colorless coatings are highly desired by industry, what can not currently be achieved by use of visible light photoinitiators. To address this issue, the development of photobleachable photoinitiating systems has become an active research field. In this review, an overview of the recent advances on photobleachable photoinitiators is provided. Face to the difficulty to access to these highly desired structures, a wide range of structures have been explored and an overview of the different structures is given.

Mn(OAc) 3 /Cu(OAc) 2-mediated reaction between ynamides, derived from oxazolidone or 3-methylindole carboxylate, and cyclic α-dicarbonyl radicals led to the one-pot synthesis of 2aminofurans. The transformation involves addition of the α-dicarbonyl radical to ynamide, oxidation to ketene-iminium, and polar cyclization steps to provide original persubstituted 2-aminofurans in good to excellent yields. This work represents the first radical route for the synthesis of furans from ynamides.

International audience; The use of broken-symmetry calculations in Kohn–Sham density functional theory has offered an affordable route to study magnetic exchange couplings in transition-metal-based compounds. However, computing this property in compounds exhibiting several couplings is still challenging and especially due to the difficulties to overcome the well-known problem of spin contamination. Here, we present a new and general method to compute magnetic exchange couplings in systems featuring several spin sites. To provide a consistent spin decontamination of J values, our strategy exploits the decomposition method of the magnetic exchange coupling proposed by Coulaud et al. and generalizes our previous work on diradical compounds where the overall magnetic exchange coupling is defined as the sum of its three main and properly extracted physical contributions (direct exchange, kinetic exchange, and spin polarization). In this aim, the generalized extraction of all contributions is presented to systems with multiple spin sites bearing one unpaired electron. This is done by proposing a new paradigm to treat the kinetic exchange contribution, which proceeds through monorelaxations of the magnetic orbitals. This method, so-called the recomposition method, is applied to a compound featuring three Cu(II) ions with a linear arrangement and to a recently synthesized complex containing a Cu4O4 cubane unit presenting an unusual magnetic behavior.

International audience; Photopolymerization is facing a revolution with the development of cheap and easily available LEDs that enable to polymerize in safe and energy-saving conditions. Bodipy constitutes a unique class of renowned dyes that are well-known for to their high photoluminescence quantum yields, their exceptional molar extinction coefficients combined with a narrow absorption and emission band. In the constant search for new photoinitiating systems activable under low-light intensity and in the visible range, bodipys have been identified as a promising scaffold for the design of photoinitiators. Recently, several difluoroborane derivatives such as boranils, squaraine-derived structures or 2phenacylbenzoxazole difluoroboranes have been proposed, expending the scope of application of photopolymerization. In this review, the different bodipys, boranils, squaraine-based difluoroborate complexes and 2-phenacylbenzoxazole difluoroboranes used to elaborate photoinitiating systems and reported to date are presented. Efficiency of the newly developed photoinitiators will be compared to that of reference photoinitiating systems.

International audience; Antimicrobial peptides (AMPs) play a key role in the external immunity of animals, offering an interesting model for studying the influence of the environment on the diversification and evolution of immune effectors., alvinellacin (ALV), arenicin (ARE) and polaricin (POL, a novel AMP identified here), characterized from three marine worms inhabiting contrasted habitats (‘hot’ vents, temperate and polar respectively), possess a well conserved BRICHOS domain in their precursor molecule despite a profound amino acid and structural diversification of the C-terminal part containing the core peptide. Data not only showed that ARE, ALV and POL display an optimal bactericidal activity against the bacteria typical of the habitat where each worm species lives but also that this killing efficacy is optimal under the thermochemical conditions encountered by their producers in their environment. Moreover, the correlation between species habitat and the cysteine contents of POL, ARE and ALV led us to investigate the importance of disulfide bridges in their biological efficacy as a function of abiotic pressures (pH and temperature). The construction of variants using non-proteinogenic residues instead of cysteines (α-aminobutyric acid variants) leading to AMPs devoid of disulfide bridges, provided evidence that the disulfide pattern of the three AMPs allows for a better bactericidal activity and suggests an adaptive way to sustain the fluctuations of the worm's environment. This work shows that the external immune effectors exemplified here by BRICHOS AMPs are evolving under strong diversifying environmental pressures to be structurally shaped and more efficient/specific under the ecological niche of their producer.

International audience; The structure of the Viologen-Phenylene-Imidazole (VPI) guest, previously shown to be bound by cucurbit[7]uril (CB[7]) with binding modes depending on pH and silver ions, has been extended by adding hydrophobic groups on the two extremities of VPI before investigations of CB[7] binding by NMR, ITC, X-ray diffraction, UV-vis and fluorescence spectroscopies. With an imidazole station extended by a naphthalene group (VPI-N), binding modes of CB[7] are similar to those previously observed. However, with the viologen extended by a tolyl group (T-VPI), CB[7] preferentially sits on station T, shuttling between the T and P stations at acid pH or after Ag + addition. The CB[7]•T-VPI complex thus behaves as a metal-actuated thermodynamic stop-and-go molecular shuttle featured by fast and autonomous ring translocation between two stations and a continuum for fractional station occupancy solely and easily controlled by Ag + concentration.

International audience; This study established a comprehensive picture of airborne metal pollution in the industrial urbanized area of the East of Algiers (Algeria). Thalli of the epiphytic lichen Pseudevernia furfuracea were transplanted from a remote unpolluted forest (Theniet El-Had) to eighteen biomonitoring sites in the Rouiba−Reghaia region exhibiting contrasting anthropogenic activities, including the wooded Reghaia Nature Reserve. Thirty-three metals and rare earths, and Br in lichen thalli were determined after 3 months exposure by X-ray fluorescence and instrumental neutron activation analysis. All biomonitored element concentrations exhibited dramatic increases compared to the control region, and calculation of contamination factor index unveiled that Sb, Pb, Ti, V, Ce, La, Ga, Cr, Cs, Cu, and Cd had the highest contamination levels in almost all the study sites. The degree of ambient pollution was assessed using enrichment factor, pollution load index, cluster analysis, and principal components analysis. A multiple correspondence analysis showed Pb, Sb, and Ga to be highly enriched with heavy contamination in all study sites, even in the Reghaia Nature Reserve.

International audience; With an increasing interest in the synthesis of (bio)degradable polymers, the synthesis of (bio)degradable vinyl polymer particles is attracting growing attention. In this work, degradable poly(methyl methacrylate) (PMMA) particles were synthesized by radical emulsion polymerization in water. A cyclic ketene acetal, 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) was used as a co-monomer to introduce cleavable ester functions into the PMMA backbone. The stability of BMDO in aqueous media was studied and the degradation mechanism discussed in order to better comprehend the use of BMDO in emulsion and understand the incorporation of BMDO into the copolymer chains. Stable latexes containing various amounts of BMDO inserted units (from 2 to 6.4 mol%) were obtained. The degradation of the resulting copolymers was carried out in a basic medium and an average molar mass loss of 90% was observed.

International audience; This chapter introduces a powerful class of machine learning approaches called kernel methods, which present an alternative to arguably more widely known neural network approaches. Kernel methods can learn even highly nonlinear problems by making an implicit transformation from a low-dimensional input space into a higher-dimensional feature space. This is in contrast to neural networks, which make explicit use of nonlinear functions to learn nonlinear problems. Alternatively, kernel methods can be seen as approaches exploiting similarities between data points. In this chapter, you will learn the fundamentals of kernel methods, their capabilities, and limitations and see how they can be used for both supervised and unsupervised learning. As usual, you can try your hand in solving chemically motivated machine learning tasks using kernel methods for several case studies.

International audience; Chemistry on-the-fly is an interesting concept, extensively studied in recent years due to its potential use for recognition, quantification and conversion of chemical species in solution. In this context, chemistry on-the-fly for asymmetric synthesis is a promising field of investigation, since it can help to overcome mass transport limitations, present for example in conventional organic electrosynthesis. Herein, the synergy between a magnetic field-enhanced self-electrophoretic propulsion mechanism and enantioselective redox chemistry on-the-fly is proposed as an efficient concept to boost the stereoselective conversion. We employ Janus swimmers as redox-active elements, exhibiting a well-controlled clockwise or anticlockwise motion with a speed that can be increased by one order of magnitude in the presence of an external magnetic field. While moving, these bifunctional objects convert spontaneously on-the-fly a prochiral molecule into a specific enantiomer with high enantiomeric excess. The magnetic field-enhanced self-mixing of the swimmers, based on the formation of local magnetohydrodynamic vortices, leads to an significant improvement of the reaction yield and the conversion rate.

International audience; Photopolymerization under visible light is an active research field whose intense research activity is supported by the recent advances in 3D and 4D printing. Within this perspective article, emerging trends in visible light photopolymerization for photocrosslinking applications will be presented. Notably, the performant multicomponent photoinitiating systems extensively used in the past are now progressively discarded in favor of mono-component systems easier to handle. The reduction of side-products formed during polymerization, the reduction of oxygen inhibition, the formation of dyes by intermolecular charge transfer interactions or the development of more ecological polymerization processes using sunlight as the irradiation source have recently been the focus of intense research efforts. Furthermore, emerging trends in processes favoring the elongation of the polymer lifetime such as self-healing will be presented and this perspective article aims at presenting the most recent breakthroughs in these attempts. To end, the future vision of visible light photopolymerization for photocrosslinking applications will be discussed.

International audience; As a local characterization technique endowed with atomic resolution, solid-state NMR spectroscopy provides unique insights on the atomic-level structure and dynamics of inorganic and hybrid materials. In particular, two-dimensional through-bond and through-space correlation experiments allow the observation of covalent bonds and proximities between identical or distinct isotopes, thus providing detailed information on the arrangement of atoms in the materials. Compared to biological and organic samples, inorganic and hybrid materials contain additional NMR-active nuclei, and notably quadrupolar isotopes with nuclear spin I ≥ 1, such as 11 B, 27 Al and 71 Ga, which are often subject to large quadrupolar interaction. Therefore, specific NMR correlation experiments have been developed to probe the local environment of these quadrupolar isotopes. We provide here an in-depth overview of correlation experiments, which have been employed for the characterization of inorganic and hybrid materials. We present first the through-space and through-bond correlation experiments to probe connectivities and proximities between identical nuclei, and then their counterparts for distinct isotopes. In both cases, we describe the experiments employed for spin-1/2 and quadrupolar isotopes. We indicate the state-of-the-art technique and the isotopes, for which they have been applied. Finally we present how these correlation NMR experiments have provided essential information on the atomic-level structure of different classes of inorganic hybrid materials, including (i) microporous materials (aluminophosphates, zeolites, metal-organic frameworks (MOFs)), (ii) metal oxide catalysts, such as amorphous silica alumina as well as supported metal complexes on alumina or silica, (iii) minerals and biomaterials and (iv) glasses.

N-acetylcysteine (NAC) has been used as an antioxidant drug in tumor cells and preclinical mice tumor xenografts, and it improves adaptive immunotherapy in melanoma. NAC is not readily bioavailable and is used in high concentrations. The effects of NAC have been attributed to its antioxidant and redox signaling role in mitochondria. New thiol-containing molecules targeted to mitochondria are needed. Here, mitochondria-targeted NAC with a 10-carbon alkyl side chain attached to a triphenylphosphonium group (Mito10-NAC) that is functionally similar to NAC was synthesized and studied. Mito10-NAC has a free sulfhydryl group and is more hydrophobic than NAC. Mito10-NAC is nearly 2000-fold more effective than NAC in inhibiting several cancer cells, including pancreatic cancer cells. Methylation of NAC and Mito10-NAC also inhibited cancer cell proliferation. Mito10-NAC inhibits mitochondrial complex I-induced respiration and, in combination with monocarboxylate transporter 1 inhibitor, synergistically decreased pancreatic cancer cell proliferation. Results suggest that the antiproliferative effects of NAC and Mito10-NAC are unlikely to be related to their antioxidant mechanism (i.e., scavenging of reactive oxygen species) or to the sulfhydryl group-dependent redox modulatory effects.