Often designed as hydrogels of modified polysaccharides (PS), biomedical adhesives are pertinent alternatives to suture. Biocompatible and offering adapted mechanical properties, their underwater adhesion needs to be strong. PolysacAdh proposes to design biocompatible hybrid hydrogels of un-modified PS by complex coacervation. Known for limiting bacteria growth, chitosan (CS), cationic PS, will be used as major constituting polymer. To form complexes with CS, hyaluronic acid (HA) or alginate (ALG) will be the guest anionic polymers. When its degree of acetylation (DA) is high enough (>45-50%), CS has a specific solution behavior: contrary to low DA CS, it soluble in aqueous solution at physiological pH. Upon addition of HA or ALG, the interpolymer interactions are favored detrimentally to the interactions with water. In order to prevent the formation of kinetic complexes, the hydrogels will be prepared from homogeneous solutions of high ionic strength (screened interactions); the latter will be dialyzed to control the formation of the interactions. The mechanical properties of the formed materials, the chemical structure of the polymers (molar mass, DA, choice HA or ALG, mannuraonate/guluronate ratio of ALG), the relative concentrations CS/HA or CS/ALG, the content of the dialysis bath (pH, presence of multivalent cations) and the presence of nanoparticles (chitin nanofibrils or CS-coated magnetite) will be studied. In contact with controlled polysaccharide-grafted surfaces (biomimetic of the extracellular matrix), the structural, mechanical and adhesive properties of these systems will be optimized. PolysacAdh is divided in three main work packages. 1) Preparation and characterization of hydrogel adhesives based on PS complexes: the conditions for obtaining hydrogels by complex coacervation will be studied. The parameters cited above will be optimized to get the most interesting mechanical and tack (on various substrates, in-air or immersed) properties. The syneresis and the mechanical properties of the hydrogels will be evaluated; the microstructure will be analyzed by scattering techniques, and Raman spectroscopy will be used to find a signature of the interactions. 2) Preparation and characterization of hybrid hydrogel adhesives based on PS complexes: focusing on the most promising hydrogels obtained in (1), the interactions will be diversified by the addition of nanoparticles, incorporated prior to the dialysis step. The aim of their presence is to reinforce the interactions and the dissipative properties of the hydrogels, as well as the interactions with the substrates. 3) Modification and characterization of PS thin films presenting a tunable adhesion: starting from CS-grafted films with various DA (already made, PhD ending in 2021), PS-coated substrates whose surface is controlled (top surface being either CS of controlled DA, HA or ALG, or mixt layers) will be developed. By using the layer-by-layer technique on the grafted CS, the substrates will present a top layer adapted for testing the hydrogel adhesives formed in (1) and (2). These surfaces will be characterized by contact angle measurements, ellipsometry and infrared spectroscopy. Their behavior in solution will also be characterized by quartz microbalance and their swelling by neutron reflectivity. The used substrates (glass, quartz, silicon) show a similar surface chemistry and will be adapted to the characterization technique. To carry out the project, a PhD student will be involved in (1) and (2) and a one-year post-doc will take care of (3). The budget also includes 22 k€ of equipment, 70 k€ of materials and functioning, 6 k€ of travels and 30.6 k€ of overheads.

ENigM proposes a family of evolutionary mimics of nitrogenase cofactor FeMo-co, for the understanding of the structure/properties relationship accounting for the exceptional reducing power of this complex structure. As a benchmark reaction, we choose the reduction of CO2, as it will enlarge and complete the information provided in the frame of N2 reduction usually considered in the field of nitrogenase mimics. This work will allow for the identification of systems able to perform the multi-electron reduction of small molecules, as the conversion of CO2 to formate, methanol or methane. The initial platform shows several structural analogies with FeMo-co: coordination sphere made of carbon and sulfur only, strongly charged carbon bridging between two iron centers. The easy modification of the ligand brings a strong modularity to our system, without the risk of denaturing the central metal-carbon interaction. A methodological ground will be established : redox and acido-basic properties of the initial platform, reactivity in the presence of CO2. This family of FeMo-co mimics will then be extended by stepwise increase of the number of metallic centers, while studying the properties of the obtained clusters.

In the current technological era, the so-called quantum era, great efforts are directed towards the study and application of quantum materials in the most varied technological fields such as quantum information processing, cryptography as well as extreme-conditions sensors development. In this context, diamond finds a leading role as a host platform for quantum color centers. Particularly, the nitrogen-vacancy (NV) color center of diamond has been widely and successfully studied since the 2000s finding extensive use in many quantum devices, including magnetic imaging, quantum information processing as well as quantum repeaters required for long-distance quantum communications. Nevertheless, the emission of the NV center remains mainly in the phonon broadened line, which limits the efficiency of the spin-photon coupling. This limit can be overcome with centers combining a group-IV atom to a vacancy (G4V center) such as silicon-vacancy (SiV), germanium-vacancy (GeV), tin-vacancy (SnV) and lead-vacancy (PbV) centers, due to the protection induced by the symmetry of the G4V defects. This allows the G4V center luminescence to be concentrated at about 80% of the total luminescence in the zero-phonon line (ZPL). This special property still exists when G4V centers are integrated into nanodiamonds (NDs), allowing them to be efficiently coupled to microcavities for quantum optics and to be employed as single photon source. NDs containing G4V centers are also suitable quantum sensors for high-pressure experiments above megabar and for life science. Our recent studies have shown that microwave assisted chemical vapor deposition (CVD) is a reliable technique allowing the synthesis of high quality NDs in large quantities, without the need for seeds or a substrate, and with considerable degrees of freedom on the incorporation of group-IV impurities (Si and Ge) from a solid-state source into NDs, and on the control of their emissivity. These as-grown SiV- and GeV-NDs have been successfully tested as stress nano-sensors up to pressures of 180 GPa overcoming the reliability limits of traditional and even NV-based sensors. In this scientific context lies the NanoG4V project, which has three ambitious objectives: (1) to synthesise high-quality quantum grade CVD NDs containing G4V color centers with a stable and highly emissive ZPL; (2) to optimize the optical properties of the quantum grade G4V-NDs by high-pressure high-temperature (HPHT) annealing and surface treatments with the aim of reducing color center’s inhomogeneous line distribution close to homogeneous lifetime limit; (3) to control the number of embedded G4V centers per ND and to demonstrate the proof-of-concept sensing: (i) quantum magnetometry under Tesla range magnetic fields and (ii) quantum sensing at stress >100 GPa for extreme sensing experiments. This new generation of quantum-grade G4V CVD NDs will find a wide range of applications, even beyond the extreme-conditions sensing, for example in the field of nanoscale thermometry, live-cell dual-color imaging and drug delivery particle tracking for medical science, that currently rely only on NDs synthesized by a complex HPHT procedure.

In this proposal, several reactivities of versatile, inexpensive and readily available titanium (II) reagent (?2-propene)-Ti(OiPr)2 will be examined. At first, its strong affinity towards alkynes will be exploited in unprecedented carbocyclization as well as cyclocarbonylation reactions to respectively access complex [5-7]-bridged vibsane and [5-7]-fused guaiane frameworks. As a proof of concept, the ability of titanium (II) to form seven-membered rings has recently been demonstrated in our laboratory through preliminary cyclocarbonylation attempts. This unique reactivity could further be highlighted through the synthesis of various other natural backbones possessing a seven-membered rings and readily applied to the total synthesis of thapsigargin and vibsatin, currently under investigation in our laboratory. In a second part, we will focus on the reactivity of Ti(II) towards alkoxyallenes and allenamides, leading to highly functionalized alkenic building blocks. To date, the direct complexation of low-valent titanium complexes onto O- or N- heterosubstituted allenes remains unprecedented, thus rendering the study very innovative. In the case of alkoxyallenes, a special focus will be devoted to readily available and relatively stable allene carbamates. From their reaction with low-valent titanium, access to highly functionalized O-ene carbamates is expected. Post-functionalization of the latters through nickel catalyzed cross-coupling would lead to stereocontrolled tri- or tetrasubstituted alkenes. A similar study will be performed with highly modular allenamines and allenamides, which should offer a straightforward access to a wide molecular diversity. As an ultimate goal, a diastereoselective version of the reaction will be proposed. Simultaneously to these survey, the unprecedented intramolecular cyclisation reactions of alkoxyallenes or allenamides having a tether bearing an alkyne function will be explored. Based on precedents in the literature on 1,2-diene-6-ynes, cyclization of 1,2-alkoxy (or amino) dien-6-ynes will be studied, leading to functionalized dienic building blocks. All along these works, a special care will be devoted to render these transformations scalable, safer and even more eco-friendly for an easier transposition to industrial scale. .

One of the strengths of the field of nanomedicine is its promise to bring new therapies to a site, by remote activation of nanomaterials to produce for example heat or chemical reactions, while reducing side effects. The current challenge of these "physical nano-therapies" is to improve their therapeutic efficacy. To do this, a modern track is to produce nanohybrids with several therapeutic functions, ultimately amplifying their therapeutic potential. Gold nanoparticles (NPs) (plasmonics), iron oxide nanoparticles (magnetic) and copper sulphide (plasmonic semiconductors) are the most modern theranostic agents. Each of these individual nanoparticle provides a number of modalities and functions. Among others; magnetic manipulation, MRI imaging, magnetic heating for magnetic NPs, phototothermia and detection for gold NPs, and finally photothermia and photodynamic therapy for copper sulphide. Here, we propose a new generation of optimized magneto-plasmonic nanohybrids combining the three materials into a single plasmonic (metal and semiconductor) and magnetic ternary hierarchical nanostructure to enable both magnetic therapy (hyperthermia) and two laser-assisted therapies (photothermia and dynamic photothermia). This ternary association, which is unprecedented, should give rise to synergistic physical properties due to interactions between the individual components, transcending their individual assets. Nevertheless, for such multifunctional "lab-on-a-nanoparticle" to have a clinical use one day, two challenges must first be addressed for, which are often ignored because of their difficulty in putting into practice: First, the lack of reproducibility of syntheses of multifunctional nano-objects once transposed on a larger scale. Then, the potential biological instability of these nanohybrids when they come into contact with the bio-environment, leading to biotransformations and biodegradations that can strongly impact their therapeutic properties. In this context, MicroNanoCell aims to (i) propose a modular microfluidic platform combining high throughput chemical synthesis of tri-therapeutic nanohybrids and screening of their biotransformations under biomimetic conditions; (ii) to compare bio-microfluidic screening with intracellular fate by proposing observations and measures, in situ, at the heart of living cells, of nanobiotransformations of hybrids; and finally (iii) to explore completely new strategies taking advantage of the complexity of the cellular environment to (re) model nanohybrids into unique bio-validated structures, either by microfluidics or by using multicellular spheroids as bio tools.