This project aims at investigating the chemistry of a-aminoendoperoxides. This class of reactive molecules has a great potential for the development of powerful and original methods in organic synthesis, and for applications to the synthesis of complex nitrogen-containing polycyclic systems. Their reactivity has been scarcely studied so far and remains essentially unexplored. The foundations of our proposition lie on the scientific expertise of the three partners, whose know-how will be engaged in a synergic fashion. Beyond the synthesis of aminocyclopropanes by the Kulinkovich-de Meijere reaction, that we know well, and the electrochemical oxidation method that we have recently developed, we will focus a great deal of our efforts to new, particularly ambitious aspects of this chemistry: the improvement and the extension of the Kulinkovich-de Meijere reaction using the advantages of electrochemistry, the generalisation of the controlled oxidation of cyclopropylamines to other types of cyclopropanes with a low ionisation potential, or the development of alternative methods relying on photocatalytic processes, even more liable to fulfil the requirements of the current global context targeted towards sustainable development. We will synthesise a range of novel natural product-like or drug-like molecules. Their biological activities will be systematically scrutinised.

This project is aimed at characterizing at the molecular and nanomolecular levels the processes involved in the translocation of cationic peptides, such as the cell penetrating peptides (CPPs), and in the permeabilization of membranes such as the antimicrobial peptides (AMPs). These studies will be conducted on different types of model membranes with various controlled phospholipidic compositions. In recent years, the interest of the scientific community for CPPs has grown because they are able to efficiently cross the cell membrane and thus to shuffle active molecules into cells. The penetration of cationic peptides through cell membranes is a complex process, associated with the high molecular diversity of the peptide sequences. Despite the development of numerous both in vivo and in vitro studies, mainly based on fluorescence techniques, the mechanism(s) involved in the trans-membrane transfer of cationic peptides is still under debate. In this context, we propose to develop a new system based on the combination of electrochemical and fluorescence techniques to analyze the consequences of peptides / lipids interactions on the supramolecular scale by following simultaneously the translocation of cationic peptides through membranes (CPPs) and the alteration of membrane permeability via the formation of pores (AMPs). We propose to develop a novel method for a fast screening of peptides families to differentiate these two extreme properties. This project is primarily aimed at developing new advances in analytical techniques via the coupling of molecular electrochemistry with electrochemical impedance spectroscopy (EIS) and fluorescence techniques such as confocal microscopy or TIRF microscopy (Total Internal Reflection Fluorescence). This project will focus on the following items: (i) synthesis of a family of cationic peptides with a fluorescent probe or redox properties and studies of bio-physico-chemical properties, (ii) electrochemical studies of the interactions between these peptides and model membranes such as phospholipid vesicles of defined composition, (iii) characterization of specific peptides / lipids assemblies by electrochemical impedance spectroscopy (EIS) and electrochemical microscopy (SECM), (iv) electrochemical studies of nano-flow cationic peptides either with antimicrobial or cell penetrating properties through a lipid bilayer suspended above a micro-hole or obtained by "patch" of giant vesicles (v) development of analytical tools combining electrochemistry and fluorescence (TIRF and confocal microscopy) to obtain kinetic information and spatial resolution on the translocation process in both ranges of short and long time.