Highlights

During this project, we explored the interconversion between distinct electronic structures, Cu(III)(phenolate) and Cu(II)(phenoxyl), in model complexes of galactose oxidase designed to catalyze the aerobic oxidation of alcohols. By optimizing the design, we synthesized and fully characterized each of the two electronic isomers using spectroscopy, electrochemistry, and quantum chemistry. We demonstrated an easy conversion of the Cu(III) species, when it serves as the starting electronic isomer, into a Cu(II) radical in the presence of a substrate. All the complexes proved to be catalysts with distinct efficiency and chemoselectivity.

The effect of the substitution of a guanine base by the oxidative lesion 8-oxo-7,8-dihydroguanine (OG) on the affinity of the DNA aptamer selected against L-argininamide (L-Rm) was studied by fluorescence anisotropy. Results shown that, depending on the OG position, the substitution either reduces, does not affect or increases the affinity. Specific oxidation of the OG-containing aptamers by an Ir(IV) salt was carried out to promote crosslinks formation with the L-Rm target. Results shown that crosslinks occur with the OG-containing aptamers but also with scramble sequences not supposed to bind L-Rm. Efforts to reduce formation of such unspecific crosslinks were only partially successful, as they failed to demonstrate that part of these adducts originated from specific recognition of aptamers towards L-Rm.

We designed mimics of rituximab, a monoclonal antibody (mAb) used to treat some lymphomas, for which CD20 antigen is well-known. For this purpose, selective aptamers of the CD20 antigen were selected by the SELEX (Systematic Evolution of Ligands by EXponential enrichment) method coupled with capillary electrophoresis (CE). After their characterization by isothermal titration calorimetric, the sequences were optimized in order to reduce their molecular weights. The most refined compounds were studied through biological experiments to validate the specificity of aptamer derivatives, from cells expressing or not the CD20 antigen. Two aptamers were selected, and dimeric constructions were performed by chemoselective ligations. These compounds should allow an increase in affinity towards the targeted cells.

Viral infections can be the source of pandemics, and the recent example of Covid-19 has reminded us that it is necessary to look for new therapeutic solutions. Antiadhesive therapy against influenza viruses, which consists of preventing the adhesion of the virus to host cells using molecular decoys, was investigated by designing nanostructured lipid particles whose surface was decorated with sialylated glycans. A bacterial process based on synthetic biology allowed the production of sialic acid-containing oligosaccharides and mimetics.1 Those molecules were used to functionalize lipid nanoparticles either by a grafting onto approach or by a one-pot formulation when assembling the nanoparticles.

The project Hybridimer aimed at (i) developing the self-assembly of hybrid nano-architectures made of QDs linked in a well-controlled manner to organic fluorophores or to gold nanoparticles (nanospheres and nanorods) by means of DNA strands, (ii) characterizing and investigating the nano-optical properties of these hybrid structures.

In this project, we made significant advances in (i) polymer synthesis (the first green synthesis of dextran methacrylate), (ii) the fabrication of dextran microneedles in which electrode integration is enabled by an original wet- and dry-state method, and (iii) demonstrating the beneficial microenvironment of dextran hydrogels on enzymatic glucose biosensors. We successfully realized the first biopolymer hydrogel-based microneedle patches with a fully integrated 2nd generation glucose biosensor for “online” detection in artificial interstitial fluid (ISF) and skin models for more than 10 days. The transdermal biosensor benefitted from the hydrogel for skin perforation and glucose-containing ISF extraction to the embedded electrodes. Cytotoxicity tests highlighted beneficial biocompatibility.

This project addresses the challenge of converting solar energy into on-demand fuel. The goal is to design enhanced hydrogen production photocathodes by developing innovative push-pull organic dyes associated with identified cobalt catalysts. Inspired by previously developed photovoltaic dyes, the project adapts properties for DS-PECs applications, strategically aligning dye characteristics with electrode material and catalyst. The synthesis of innovative dye-catalyst dyads yields promising outcomes, featuring strong visible-range absorption and effective coupling with NiO and known catalysts. These advancements, along with the development of lithium-doped electrodes, showcase superior photo-electrocatalytic performance compared to literature references.

The CAZy database houses over 600,000 DNA sequences for glycoside hydrolases (GH), with less than 3% characterized for function and only 0.23% having a known structure. The diverse GH biodiversity presents potential biological targets for addressing diseases and plays a role in bio-catalysis for transforming bio-sourced glycopolymers in industries. The project focused on developing a method to selectively identify α-glucosidase enzymes in biological extracts. Bio-chips functionalized with iminosugars, nitrogen-containing glycomimetics, were employed for their selectivity toward α-glucosidases using surface plasmon resonance imaging (SPRi).

Dynamic nuclear polarization (DNP) significantly improves the sensitivity of solid-state NMR by transferring the large magnetization of added unpaired electrons to the nuclei of the sample, thus increasing their NMR signal.