UltimSMM project proposes original synthetic pathways to generate ideal lanthanide-based sandwich metallocene complexes towards ground-breaking insights into the field of lanthanide Single Molecule Magnets (SMMs). Bulky cyclopentadienyl-based trivalent dysprosium complexes have recently led to impressive progress in the field of lanthanide SMMs, however, so far the perfect geometry has not been obtained in these sandwich complexes (Cp-Dy-Cp angle of 180°). This project aims to synthesize such unprecedented linear trivalent complexes based on pentaarylcyclopentadienyl ligands starting from zero-valent lanthanides and exploring straightforward C-FG bond cleavage (FG = P, Si, halides) routes driven by prospective quantum chemical calculations. The reactions will be performed in solution or, for the first time, under solvent-free ball-milling techniques. Variation of the aryl groups, introduction of heteroelements in the cyclopentadienyl ring and employing lanthanide metals beyond dysprosium are among the target modifications, providing complexes designed to lead the race in the field of high-temperature nanomagnets.

The combination of Bone Marrow Mesenchymal Stromal Cells (BM-MSC) with active injectable carriers brings about innovative solutions to current issues in the field of tissue engineering. In particular, repair of adult articular cartilage lesions remains a clinical challenge because of the limited self-healing capacity of cartilage. We demonstrated previously that the open porosity of homemade collagen microspheres allows for the entrapment and progressive release of TGF-β3, which efficiently triggered the chondrogenic differentiation of BM-MSC in vitro and in vivo, and the production of neo-cartilage tissue. However, one major hurdle in MSC-based therapies for cartilage repair is their late hypertrophic differentiation and subsequent tissue calcification, characterized by the secretion of specific markers such as type X collagen, alkaline phosphatase, osteocalcin and metalloprotease 13 (MMP13). To tackle this challenge, we identified Runx2, which plays a central role in chondrocyte hypertrophy, as the main molecular target to be repressed. Indeed, Runx2 has been widely described to up-regulate the expression of hypertrophic markers. We previously demonstrated that the transient down-regulation of this factor can be achieved with a specific siRNA targeting Runx2. Hence, the strategy of the Spacecart project is to use the transient down-regulation of Runx2 with siRNA (siRunx2) to prevent calcification and ultimately bone formation. We intend to deliver siRunx2 from collagen microspheres also used as an injectable support for BM-MSC and as a TGF-β3 reservoir. However, efficient down-regulation of Runx2 with siRNA requires transfection vectors to bring the nucleic acid to its nuclear target within the cells. Also, to maintain efficient chondrogenic differentiation of BM-MSC, it is important that Runx2 be repressed only after induction of the chondrocyte phenotype, i.e. approximatively day 14, thus calling for delayed delivery of the siRNA. For this project we have designed modified DOTAP-DOPE lipoplexes as the nucleic acid vector. These vectors will be loaded into collagen microspheres and anchored to the matrix via MMP13-sensitive peptides. The action of MMP13 secreted by MSCs will therefore trigger the local delivery of siRNA to the cells at the early stage of hypertrophic differentiation commitment. This cell-elicited spatio-temporal control of siRNA release is expected to help maintain the phenotype of mature chondrocytes in the long term and achieve fully functional hyaline cartilage regeneration. Our work plan includes three experimental tasks dedicated to 1) the design and synthesis of an optimal MMP13 peptide substrate and its use as cleavable linker between the collagen microspheres and siRNA vectors, 2) the investigation of the down-regulation of Runx2 in BM-MSC and its outcome on in vitro chondrogenesis and hypertrophy inhibition and 3) the study of neocartilage production in vivo in the absence of ossification in the long-term. Our consortium gathers complementary expertise in the fields of biomaterial elaboration and functionalization, peptide design and synthesis, and MSC-based therapy of cartilage pathologies. The main originality of our research project is to use the secretion of MMP13 by BM-MSC undergoing hypertrophic differentiation, to locally trigger the delivery of an anti-hypertrophic siRNA. We believe that our integrative approach is original and has a strong innovative potential. In addition, such highly specific self-induced retro-control of the cell behavior can potentially be transposed to other therapeutic indications by adapting the peptides to the enzymatic secretion profile of the specific cells. Therefore, we expect that Spacecart will have an impact on the broad community in the field of biomaterials and tissue engineering.

The use of renewable resources is essential for a sustainable society. Developing clean catalytic processes to produce value-added chemicals from renewable materials such as wood or plants has become a major goal for chemists. The bio-feedstocks issued from lignocellulose after either enzymatic fermentation or acidic deconstruction consist mainly of water-soluble molecules containing many oxygenated groups ((di)acids, alcohols, ethers), which must be subsequently transformed to find applications as monomers, solvents, etc. For this purpose, the design of new water-stable catalysts able to withstand rather harsh reaction conditions in term of pH, temperature and pressure is required. The NHYSCAB project aims at the synthesis of hydrothermally stable promoted metallic catalysts, based on a supported noble metal (e.g. Pd, Ru) modified with an oxophilic promoter (Re or Mo). They will be used for catalytic hydrogenation/hydrogenolysis of biosourced molecules in aqueous phase, at temperatures in the range 100 to 200°C and hydrogen pressure in the range 50 to 150 bar, at acidic to neutral pH. This project is based on the collaboration between two complementary public partners, IRCELYON (coordinator) and ICGM Montpellier, which are internationally recognized for their expertise in the fields of biomass catalytic upgrading and of non-hydrolytic sol-gel (NHSG) synthesis of mixed oxides, respectively. The first part of the project consists in the design of advanced mesoporous catalyst supports using the NHSG process which offers powerful synthetic routes to hydrothermally stable mesoporous oxides (TiO2, ZrO2) and mixed oxides incorporating the promoter species (Re-Ti, Mo-Ti), which after an appropriate thermal treatment are dispersed at the surface of the oxide. The hydrothermal stability of these supports will be assessed under the reaction conditions. Noble metal will be deposited on the stable supports with well-defined compositions and structures in order to prepare efficient promoted metallic catalysts. The second part concerns the evaluation of the synthesized catalysts in the reference reaction of aqueous-phase hydrogenation of biosourced acids (succinic acid and levulinic acid) to the corresponding diols (1,4-butane- and 1,4-pentane- diols). The catalysts will also be evaluated in the challenging hydrogenolysis of tetrahydrofurfuryl alcohol from the furfural platform into the corresponding 1,2- or 1,5- pentanediols. The expected products can find many applications, including as monomers. The design of well-defined, thoroughly characterized solids is essential to optimize the selective synthesis of targeted chemicals. Therefore, extensive characterization of the solids (supports and catalysts) will be performed at different stages (oxides, mixed oxides, supported metallic catalysts, before and after reaction) and their stability will be investigated under the reaction conditions. These will allow us to determine the texture/structure/composition of the solids, to validate their stability and to correlate the characteristics of the catalysts and their performance. To reach the highest activity or selectivity, the study will focus not only on the catalyst design but also on the optimization of reaction conditions. After screening of catalyst compositions using a batch reactor, the catalytic reaction will be conducted in a continuous trickle-bed reactor to further study the stability of the selected catalytic systems.

Metal-Organic Frameworks (MOFs) form a family of porous inorganic-organic ordered hybrid materials which have generated huge interest in the scientific community. Whilst sorption, magnetic, catalytic and drug delivery properties have been largely documented, the basic mechanical properties of these materials have not received as much interest. However, the fact that several structures are highly flexible may be of interest to exploit as dampers or springs as an alternative to previous work carried out on hydrophobic silica based materials. The advantage of MOFs being that the almost infinite possibility to modulate the structure and chemical/physical properties of these materials means that the mechanical properties can equally be tuned. The aim therefore of this fundamental project is twofold : 1) To study the thermodynamic and mechanical properties of selected flexible MOFs in view of (i) establishing pore volume phase diagrams as a function of pressure and temperature, (ii) determining the transition energies between the various phases and (iii) characterizing the structural behaviour under operating conditions up to high temperature and moderate pressure, to compare with theoretical calculations; 2) To evaluate the possibility of using these materials for mechanical storage of energy as dampers or springs. This challenging interdisciplinary project that involves the synthesis of materials, the characterization of the properties of interest and modelling, will be conducted by a subtle combination of innovative experimental tools and advanced molecular simulation approaches, which is expected to yield breakthrough in this domain. It will also bring microscopic insight into the mechanism in play during the phase transition under thermal and mechanical stimuli.

The SURHYMI project aims at developing a sustainable and integrated approach for the synthesis of hybrid mesoporous films and membranes densely and homogeneously functionalized by polymers, designed as platform materials for the elaboration of micropollutant removal devices. The control of the textural and chemical properties of the supported films and membranes (pore diameter and topology, and functions (acid, basic, cyclodextrin) in the mesopores), will allow to evaluate their performances in the reversible sorption of anionic, cationic and hydrophobic micropollutants based on electrostatic interactions or host-guest complexes. Novel polyion complex micelles (PIC) as well as host-guest inclusion complex (InC) micelles will be evaluated for the first time for their ability to controllably form a variety of ordered mesostructures by the sol-gel route, first as powders by macroscopic precipitation and then as films and membranes by deposition-evaporation. PIC micelles will be formed by electrostatic complexation between double-hydrophilic block copolymers (DHBC) and oppositely charged polyions, auxiliaries of micellisation. Poly(acrylic acid) and poly(aminoethylacrylamide) based DHBCs will be synthesized by RAFT in acidic media in order to protect the chain-transfer agent. Then, they will be used as platform polymers for the preparation by amidation reactions of a range of new DHBCs with beta-cyclodextrin (CD). Polymers with beta-CD functionalities will enable the formation of inclusion complex micelles (InC) with ditopic/multitopic guest species, which will be studied as silica structuring agents. PIC and InC assemblies will be evaluated for the first time as structuring, functionalizing and porogenic agents of functional mesoporous supported films and membranes. The new methodology developed should allow the preparation of materials whose mesopores will be intrinsically functionalized in a homogeneous and dense way by the targeted and previously prepared functions. The films will be prepared by evaporation induced assembly (EISA process). Depositions will be performed first on dense substrates, then on porous substrates. The disassembly of PIC and InC will allow the elution of the micellisation auxiliaries and will reveal the intrinsic functionalization of the layers with the three types of functions, acid, basic, and CD. The porous textures, thicknesses, density profiles and permeability of the functional films will be characterized. The influence of these properties will be evaluated for the sorption of model micropollutants as a function of physicochemical parameters (pH, concentration, ionic strength). Four organic micropollutants (hydrophilic cationic and anionic, as well as hydrophobic) were selected to demonstrate the specific and reversible character of the sorption mechanism in hybrid mesoporous silica-based platform materials. The kinetics, reversibility and repeatability of the sorption process will be studied as well as the chemical and structural recyclability and aging of the adsorbent materials. These results will be transferred to supported membranes to evaluate their filtration performance, chemical and structural stability and the mechanical properties of the prepared membrane materials.