Photoelectrochemical hydrogen production has made huge progress since the first report of TiO2 ability to split water by Fujishima and Honda in 1972. Still photoelectrochemical cells remain at the lab level, except for one prototype of photo-assisted electrolyzer developed by ENGIE’s R&D laboratory CRIGEN and a US start-up, Nanoptek, now at the pilot level, that exploits a TiO2 photoanode to enhance the performance of an alkaline water-splitting electrolyzer. While the former system requires electrical feed from the grid, the PROSPER-H2 project aims at developing an alternative technology for a self-sustained water-splitting photoelectrochemical cell producing hydrogen out of the grid through (i) developing novel electrodes and photoelectrode materials to achieve high overall photoelectrochemical performances and stability for light-driven hydrogen production, (ii) engineering the system of materials to make a safe system working under neutral or near neutral conditions, (iii) modelling the whole device as well as optimizing light management and finally (iv) prototyping two photoelectrochemical cells at scale and testing them under realistic conditions. PROSPER-H2 will combine efforts of ENGIE and 5 laboratories at CEA with expertise in electrocatalysis, photonics, photo-electrocatalysis, materials science, multiscale-multiphysics modelling and chemical engineering to tackle the key above-mentioned scientific challenges and produce two pre-industrial PV-biased and tandem PEC prototypes for the decentralized production of solar hydrogen.Furthermore, the consortium will address RSE implications of such technology through life-cycle analysis, technoeconomic and sociotechnical studies.

Although sugars play a crucial role in many biological processes, their uses in therapeutics remain limited due to their low stability. That’s why organic chemists are constantly pushed to develop new access to original analogues. In particular, replacement of natural anomeric link by C-C mimics (C-glycosides) is widely explored due to their higher chemical and enzymatic stability as well as their conformational similarity compared to natural C-O and C-N analogues. These specific aspects have made these structures potentially valuable enzyme inhibitors. Current synthetic routes of C-glycosides involve several steps and use frequently strong bases, which narrow their development. This last decade, access to complex molecules via C-H functionalization reactions is became very attractive since this strategy avoid to go through pre-functionalized intermediates. In order to circle regioselectivity issues inherent to these transformations, the uses of directing group is commonly chosen in C-H functionalization catalyzed by metallic complexes. Despite the interest of this type of reaction, examples of metal-catalyzed C-H functionalization of sugar-type substrates are scarce and involve in the most of the case intramolecular radical processes. In this project, our goal is to develop new general and efficient synthetic routes to C-aryl-glycosides of interest via metal-catalyzed C-H functionalization reaction of the C-H anomeric bond. These structures showed already several interesting biological activities in diabete 2 treatment for example. The challenge associated to this project is to mono-functionalize complex sugar substrates possessing many similar C-H bonds. Our strategy consists in introducing a directing group on the desired starting glycoside. The position of this directing group is crucial and will be soundly chosen. The first part of the project is interested in the synthesis of C-aryl-glycoside carboxamides as N-acetyl-glycoside mimics. These structures will be obtained via a metal-catalyzed C-H functionalization reaction of unsaturated glycal substrates directed by an amido-group in C2 position. This directing group will be previously installed via a pallado-catalyzed aminocarbonylation process recently developed in our laboratory, between a 2-iodoglycal and an amine in presence of « CO » source. The second part of the project tends to develop access to C-aryl-glycosides via a metal-catalyzed functionalization from saturated glycosides. Our strategy consists in introducing a silylated directing group, easily installed on hydroxyl, on the anomeric hemiacetal function. This type of directing group offer the possibility to access to two types of structures: C-glycosides and keto-glycosides, depending on the cleavage method used at the end of the reaction. In a third part, due to environmental concerns which tend to reduce number of synthetic steps in complex molecule synthesis, the development of metal-catalyzed dehydrogenative C-H functionalization reactions will be planned on the same starting substrates envisaged in the two first methodologies. In this last part, the objective is to couple our glycosides with non pre-functionalized aryl partners. Post-functionalization, deprotection of obtained compounds as well as application of the developed methods to the synthesis of molecules of therapeutical interest will be investigated at the end of each part.

Since the outbreak of Ebola, in 2014, MMN-ESPCI and CIBU-PASTEUR have worked together to develop a portable test, dedicated to the detection of nucleic acids of pathogens, viruses and bacteria, exploiting the latest developments of microfluidic paper technology and molecular diagnostics. Together, we published three papers and delivered one patent. Since then, the collaboration ESPCI-PASTEUR has been very active. Recently, we succeeded to demonstrate a portable system, based on LAMP-QUASR (Loop Amplification coupled to a sensitive detection of the amplicons) in which RNA extraction is performed, amplified, the product of the reaction being detected with a smart phone. Important to note, all the components of the reaction are lyophilized, minimizing the number of pipetting steps and enabling storage at room temperature. Since February 2020, we work at applying our technology to the detection of the SARS-COV2 virus. Our technology will allow to perform millions of decentralized tests, with a minimum of equipment, thus accessible to medical offices, small labs or small clinics, with a 45 min response, sensibility and specificity comparable to PCR, with no need to send the sample to medical laboratories equipped with expensive PCR machines. The objective of the proposal is to develop our effort on this technology, including a feasibility study (prototyping/selection of reagents/first testing on clinical COVID sample), development phase (optimization/verification) and industrialization toward mass production enabling its use at large scale for the benefit of the population and the acceleration of a return to a normal situation.

Despite important progresses made over the past few years towards the development of new molecular structures the electrocatalytic reduction of CO2, such catalysts still mostly remains far from potential industrial applications, mainly due to a lack of control of the reactivity and stability of the molecular centre. MatriCORe will focus on the development of new macromolecular architectures for CO2 reduction, through a bio-inspired approach. The project will consist in integrating, within multifunctional polymer structures, various chemical groups capable of assisting the molecular centre during catalysis, mimicking the peptidic network around an enzyme active site. Integration of these matrices to electrode materials will allow rationalising the impact of each assisting function to the catalysis. This strategy will enable the generation of new molecular assemblies for efficient electrocatalytic CO2 reduction.

Although life is intrinsically related to biochemical and structural changes over time, the focus of structural biology has always been the detailed investigation of the highly populated compact ground states of biological macromolecules, yielding a static picture, and neglecting the dynamic nature of biology at the molecular level. At ambient temperature, proteins sample an ensemble of conformations as a result of their thermal energy. It is well known that states that are only sparsely and transiently populated can play critical roles in biochemical processes such as ligand binding, enzyme catalysis, protein misfolding, and amyloid formation. The multiplicity of states that are accessible to a protein is best described by a multidimensional energy landscape that describes the relative probabilities of the conformational states (thermodynamics) and the energy barriers between them (kinetics). The energy landscape not only depends on the particular protein but also on its environment. The interior of a cell, of course, is an extremely complex and crowded environment in which proteins and other macromolecules are present at concentrations of 300-400 mg/ml. The protein energy landscape also provides a description of the various conformtions that are sampled by a protein in the process of folding. Depending on the particular protein, there may be intermediate states represented as subsidiary minima on the energy landscape, and there may be more than one pathway for a protein to fold to its native state conformation. The folding problem of how proteins find their unique native states simply from the information contained within their amino-acid sequence remains a central unresolved question of modern science. Closely related to the protein folding problem is the question in which way proteins or protein fragments self-assemble into ordered functional macromolecular complexes, or insoluble aggregates associated with amyloid disease. It is generally believed that precursors of fibril formation are not the compact native protein states, but partially unfolded excited states that are populated at low level under native physiological conditions. Among the techniques nowadays available for detailed structure investigation, liquid-state NMR has the particular advantage of allowing the study of molecular structure in native-like solution conditions, cellular extracts, or even living cells. Multidimensional NMR is also ideally suited to access molecular dynamics and kinetics occurring over a wide range of time scales from picoseconds to seconds, hours and days, together with atomic resolution information for excited protein-state conformations. In addition, NMR enables atomistic descriptions of highly flexible conformational ensembles inter-converting on a sub-milliseconds time scale, as commonly encountered in natively unstructured protein fragments or partially denatured protein states. This versatility makes liquid-state NMR a unique tool for studying the 'invisible' manifold of high-energy excited molecular states, as well as conformational preferences in otherwise unstructured molecules. The research project proposed here aims at combining and further developing multidimensional NMR methods to study the structural, dynamic, and thermodynamic features of low-populated excited or transient intermediate protein states of different protein systems implicated in various biological functions. The high-resolution NMR studies will be complemented by low-resolution spectroscopic methods: fluorescence, circular dichroism, absorbance, and infrared correlation spectroscopy. These low-resolution techniques provide additional kinetic information of high precision for one or a few sites in the molecule, or an average of the entire system. The combined interpretation of different spectroscopic data shall provide a more comprehensive picture of the energy landscapes of these proteins, and thus a better understanding of the mechanisms of molecular recognition, protein folding and misfolding.