MARCEL 2.0 proposes an original concept where metallic nanocatalysts (Au, Ag, Cu nanoparticles) are functionalized with molecular hosting cavities bearing metallic complexes in order to direct the reactivity in ORR and CO2RR electrocatalysis. Both of these processes are complex and require efficient and highly selective catalysts as the metalloenzymes. Inspired form such biological systems whose functioning is based on confinement and supramolecular effects, MARCEL seeks the rational control of forming and stabilizing intermediates to guide specific reaction pathways. This innovative design that relies on surface supramolecular effects will be further combined to plasmonic effect in order to enhance the electrocatalytic performance. The reactivity and interfacial phenomena will be thoroughly investigated by combining experimental (electrochemistry, in situ spectroscopies) and computational analyses.

The Mol-CoSM project, gathering three complementary french groups (Brest (1), Versailles (2) and Nancy (3)), deals with the design of new multifunctional complexes combining, in a synergetic way, molecular switching and fluorescence. Thus, in addition to the extensive synthetic work to the design new series of multifunctional systems, this project has three orientations: (i) the control of the fluorescence yield according to the nature of the fluorophore; (ii) the control of the switching parameters, such as the transition temperature and the cooperativity; (iii) the understanding of the electro-vibrational interactions between the fluorescent motif and the SCO center, so as to enhance the bi-functionality, to produce thermal bistability, both on the magnetic and fluorescent properties. The final objective is to propose new systems with enhanced multi-functionalities for potential applications such as new generations of magneto-optical switches and molecular multi-sensors.

CATHOMIX explores the harnessing of living, free and renewable electroactive microbial catalysts as mixed biofilms on biocompatible cathodes efficiently delivering electrons directly or in the form of H2 to a N2 fixing metabolism (the biological reduction of N2 to ammonia NH3). The ultimate objective of the project is to characterize and demonstrate in the laboratory the generation of ammonium (NH4+) at a microbial cathode powered with renewable electricity while using the microbial catalysed oxidation of waste at the anode of the device. At the cathode, the reduction of H2O to H2 is catalyzed by designed inorganic or biomimetic electrocatalysts based on non-noble metals. The cathode will be colonized with a mixed biofilm selected and enriched to target the fixation of N2 by the direct use of electrons or indirectly through electrogenerated dihydrogen. CATHOMIX will cross TRL 1-2 to TRL 3-4. The intermittence of power on energy efficiency and microbial ecology will be studied, quantified, modelled and managed.

Methane is a greenhouse gas that remains in the atmosphere for approximately 9-15 years. It is over 20 times more effective in greenhouse effect than carbon dioxide over a 100-year period. Methane is also a primary constituent of natural gas and an important energy source. To reduce its greenhouse gas effect and to increase its potential as a petroleum alternative for fuels and in the petrochemical industry, its transformation into a liquid form such as methanol is of current interest in chemistry. Currently, industrial methanol production is accomplished by the steam reforming of methane, which requires high temperatures and pressures. Therefore, alternative processes such as the selective direct oxidation of methane to methanol are of considerable interest. However, methane has the strongest C-H bond of any hydrocarbon (104 kcal/mol), thus its selective oxidation to methanol without further oxidation is extremely challenging. In nature, methane monooxygenases (MMO) accomplish the direct conversion of methane into methanol at ambient temperature and atmospheric pressure allowing the harnessing of methane as an energy source and for the synthesis of the molecules required for life. MMO exists as soluble and particulate forms. The soluble enzyme (sMMO) contains a (mu-oxo)FeIIFeII active site which reacts with dioxygen to produce a bis(mu-oxo)FeIVFeIV as active species in methane oxidation. Inspired by sMMO active site, chemists have attempted to understand or reproduce the reactivity of sMMO by studying small metal complexes as active site models. Thanks to this approach, several structural and functional models for the sMMO active site, have been reported providing a better understanding of sMMO functioning and mechanism as well as the development of promising catalysts for oxidation. Compared to sMMO, the knowledge on the particulate form (pMMO) is recent and pMMO has been the subject of a controversy about the metal content and the structure of its active site. Nevertheless, the most recent results propose a dinuclear copper center, which reacts with dioxygen to produce a Cu2/O2 as active species in methane oxidation such as (mu-eta2:eta2-peroxo)CuIICuII or bis(mu-oxo)CuIIICuIII. However, DFT calculations suggest that a 1-electron reduced mixed-valent bis(mu-oxo)CuIICuIII species has greater oxidizing power to cleave the methane C-H bond rather than either the symmetric (mu-eta2:eta2-peroxo)CuIICuII or bis(mu-oxo)CuIIICuIII. This proposal aims at designing new copper-based catalysts efficient for alkane oxidation. The design of theses new catalysts comes from the inspiration of the structure and the functioning of the copper-containing pMMO. A mixed-valent bis(mu-oxo)CuIICuIII species has been recently proposed to occur as highly reactive intermediate during the hydroxylation of methane into methanol. The first part of COMEBAC will be devoted to the synthesis of ligands able to stabilize a mixed-valent bis(mu-oxo)CuIICuIII species in order to characterize it by spectro-electrochemistry. The second step will concern the study of its reactivity toward organic substrates (alkanes, alkenes …). Electrochemical studies coupled with theoretical calculations, as an electronic mapping, will be involved in all aspects of the project, towards the conception of the best ligands for the stabilization of the mixed-valent (mu-oxo)CuIICuIII species and optimization of the reactivity in alkane oxidation. COMEBAC is a basic research project the results of which can be reasonably considered to impact the field of hydrocarbons remediation or that of aliphatic alcohols production, and even more generally in oxidase/oxygenase mimicry.

Rational: Venous thromboembolism (VTE), clinically presenting as deep vein thrombosis (DVT) or pulmonary embolism (PE), is the third most frequent acute cardiovascular disease after myocardial infarction and stroke, and is associated with high mortality (around 10%). The frequency and the severity of VTE have not changed over the past 20 years despite major advances in diagnostic tests and therapeutic improvement. Particularly, distinguishing recurrent VTE from residual clot is of foremost importance. Indeed, therapeutic implications differ significantly whether the patient is facing an acute VTE versus a relatively passive residual thrombus whereas it remains challenging with the current imaging modalities to have a definite diagnosis. In deed, current imaging techniques although well validated for the exclusion of VTE at the acute phase, do not provide any information about the composition of the thrombus and can not distinguish between residual and newly formed clots. Molecular imaging has emerged at the end of the last century as a new in vivo imaging method allowing the visualization, characterization, and measurement of biological processes at a cellular or molecular level. In the setting of VTE, molecular imaging allows noninvasive direct targeting of the thrombus with high specificity and sensitivity with a potential of whole-body imaging. Targeting directly the active venous clot may allow a direct visualization of a specific part of the thrombus. Many studies since the end of the 1970s have already investigated the role of molecular imaging for the diagnosis of VTE targeting various contributors of thrombosis, as well as the different components of the venous clot. However, studies were performed using conventional planar or single photon emission computed tomography (SPECT) imaging, resulting in insufficient spatial resolution and detectability. Nuclear medicine and molecular imaging have undergone a technologic revolution with the development of an increasing array of new positron emission tomography (PET) tracers. Technical advantages of PET compared to SPECT include higher sensitivity, higher spatial resolution (4 mm for PET vs. 12 mm for SPECT), and superior quantitative capability. Objectives: The objective of this project is to develop new radiotracers for VTE diagnosis using PET technology, derived from tracers already assessed in humans with SPECT technology and to test them in pre-clinical models of thrombosis. Research hypotheses and methodology: We have selected three biomolecules corresponding to different constituents and steps of thrombus formation, that may potentially distinguish fresh (i.e recurrent VTE) from old thrombi (i.e residual clot), which is of foremost importance for clinicians. The challenge of this project is to find the appropriate combination of [targeting biomolecule/radionuclide with the suitable half-life/corresponding radioisotope-chelating agent] for a safe use and to propose the relevant biological and radiopharmaceutical approach from in vitro to in vivo studies.The three radiotracers will be produced by combining selected biomolecules targeting early and late thrombotic processes, and labeled with 64-copper (WP1). The binding capacity of synthetized radiopharmaceuticals to venous clots will be evaluated using ex vivo models of thrombus formation (WP2). Biodistribution, pharmacokinetic and binding capacity of synthetized radiopharmaceuticals to a clot will be evaluated in a mouse model of venous thrombosis (WP3). Expected results: We expect to improve the sensitivity of existing tracers using PET technology that will greatly facilitate their translation into humans, leading to the development of the world’s first PET radiopharmaceutical dedicated to recurrent VTE diagnosis with high specificity and sensitivity that could strongly modify patient care.