The direct transformation of C-H bonds into C-N bonds via nitrene insertion is an atom-economical reaction that allows a streamlined access to highly valuable molecules for life sciences and fine chemicals. Dirhodium complexes are among the best catalysts for the C(sp3)-H insertion of nitrenes into alkanes, despite intensive research efforts toward the use of more abundant transition metals. Whereas the catalytic intramolecular nitrene insertion occurs with very good levels of regio- and chemo-control, reactivity and selectivity in the intermolecular version remain a challenge. The design of chiral catalysts able to efficiently discriminate between two enantiotopic C-H bonds under oxidizing conditions is also challenging. This proposal aims to tackle these issues through the incorporation of redox-active ferrocenyl ligands into dirhodium catalysts. The study should allow us to gain a better understanding of the intermolecular C-H amination mechanism from the angle of catalyst design and the influence of the ligands’ electronic properties on their efficiency and selectivity. It should also make it possible to carry out the reactions with softer oxidants than classical hypervalent iodine compounds via the electron-relay of ferrocene, and to give access to new chiral catalysts. The CHamRhOx project is mainly of fundamental nature, aimed at removing bottlenecks and extending the applicability of the intermolecular C(sp3)-H amination reaction. It particularly addresses problems of relevance to sustainability since it associates the use of – potentially asymmetric - catalysis with the objective of using more ecofriendly reagents. Preliminary results, recently obtained by a team of the consortium, showed that a dirhodium complex bearing a ferrocenyl ligand could perform an intermolecular C-H amination reaction, while keeping the same level of diastereoselectivity as the reference complex without ferrocene. The project will be implemented by a multifaceted approach that includes synthesis, coordination chemistry, analytical studies and thorough catalytic studies of C-H amination.

"Copperation" project aims to develop and synthesize fluorescent ligands capable of selectively extract copper (I) ions (Cu) contained in the amyloids-ß peptides (Aß), thus inhibit the production of toxic reactive oxygen species (ROS) in the context of Alzheimer's disease. The fluorescence properties will allow (i) in cellulo complex localization studies of these molecules; (ii) mechanistic studies during the extraction processes of Cu from Aß and during the evaluation of the impact of the ligands on ROS production (in vitro and in cellulo). The ability of ligands to rebalance Cu between intra- and extracellular compartments for therapeutic purposes will also be studied, as well as their effects on restoring cell survival under or without oxidative stress.

When molecules are strongly coupled to confined electromagnetic fields within micro- and nano-structures (e.g. Fabry-Pérot or plasmonic nanocavities), new hybrid light-matter states – known as polaritons – are formed; the coupled {molecules + cavity} system having to be thought as a single entity with new energy levels and exhibiting new physico-chemical properties. This field of “molecular polaritonics” has seen a spectacular progress in the past decade and represents today a powerful strategy to explore the synergetic effects that can exist between optical resonant cavities and molecular bistability property. In this context, the SCOPOL project aims at achieving and exploiting light-matter strong coupling of spin-crossover (SCO) molecules, which exhibit reversible switching between their low-spin (LS) and high-spin (HS) electronic configurations, to electromagnetic modes within various optical nanocavities. The aim of the project is twofold. (1) On one hand side, we seek to use the SCO bistability to switch between strong-coupled and uncoupled regimes in the cavity through various external stimuli (temperature, light irradiation, etc.) and then scrutinize possible applications in reconfigurable/adaptive optics. (2) On the other way around, we seek to use the strong-coupling regime, which deeply modifies the energy landscape of the coupled system, to fine tune the phase stability (spin-transition temperature, abruptness of the transition, hysteresis width) and the spin-state switching properties of the SCO molecules. This property could be the “Holy Grail” in the spin-crossover field allowing, for instance, custom-designed spin-transition properties or light-induced spin-state switching at room temperature. SCOPOL is a strongly interdisciplinary project, which is based on the complementary skills of the host teams at the LCC-CNRS and LAAS-CNRS, combining in-depth knowledge of spin-crossover nanomaterials and a cutting-edge nanotechnology platform for photonic device fabrication. In this frame, conventional SCO-embedded metal-mirror-based Fabry-Pérot (FP) and plasmonic cavities will be fabricated, with purposefully adjusted size and shape, to explore the interplay between SCO and light-matter strong coupling. As a second step, more advanced nano-photonic devices will be developed (FP resonators with 3D cavity mode, sub-wavelength-grating structures), with higher quality factors and further confined cavity volume, which will not only allow for more flexibility in the integration and control of SCO materials, but also provide scope for proof-of-concept applications. In a third step, the tuning of SCO properties will be investigated, more specifically by coupling selected molecular vibrational transitions to cavity modes (in the infrared spectral region), as a means to control the LS-HS energy gap and thus the switching properties of SCO molecules. SCOPOL is an exploratory fundamental scientific project, which is also motivated by future technological applications. In particular, using a novel paradigm (formation of hybrid light-matter states), this project aims to turn these switchable molecules into active elements in photonic devices, which will open new avenues for a variety of applications, especially in the context of spatial light modulator technologies as well as for photonic integrated circuits.

Inspired from nitrogenases, chemists focus on implementing mild artificial N2-fixation. The unique reactivity of these enzymes arises from the combination of a bimetallic Fe unit, activating N2 via a “push-push” mechanism, with H-bond donors (Lewis acids), interacting with N2 and enhancing its reactivity via a “push-pull” pathway, and sulfur ligands with acido-basic properties propitious for catalysis. PUNCh proposes to combine these three elements in nitrogenase model chemistry, with expected beneficial effects for catalytic applications. Its strategy includes the investigation of bimetallic thiolate-bound complexes for the activation of N2, structure-function correlation studies on group 6 N2-complexes with p-block Lewis acids, and the synthesis of “mixed” metal-thiolate/group 6-N2/Lewis acid systems. All the required skills are available in the consortium: synthesis/reactivity/characterization of complexes, electro/photo- and quantum chemistry.

The fight against malaria faces to the emergence and massive spread in Asia of resistance of the parasite Plasmodium falciparum to the antimalarial drugs artemisinins. Artemisinins are the core component of Artemisinin-based Combination Therapies (ACTs) combining an artemisinin derivative with another antimalarial molecule. In 2020, artemisinin-resistant parasites are now also reported in South-America, and in Africa where by 2040 artemisinin resistance will lead to an increase in the incidence of several million cases. Worryingly no current drugs can replace ACTs in the short to medium term. To date, artemisinin resistance is only tracking once emerged. My project aims to explore the biology of parasites under artemisinins pressure in order to identify predictive markers of the acquisition of artemisinin resistance in the parasite Plasmodium. Such tools could alert as soon as possible to improve decision-making process for malaria treatment policies.