Redox enzymes are at the heart of a wide range of bioenergetic processes essential for all living organisms. They operate under mild conditions with high specificity, low overpotential and high turnover rates. Deciphering “how redox enzymes operate” is a prerequisite before harnessing their outstanding properties. Surface Enhanced InfraRed Absorption (SEIRA) spectroelectrochemistry probes redox enzymes in situ and in operando revealing information on secondary structure elements, orientation, catalytic mechanisms, redox chemistry and functionality. However, despite this outstanding potential, SEIRA spectroelectrochemistry faces limitations mainly arising from the nature of the biological samples. In fact, it is nearly impossible to exclusively rely on intrinsic IR markers of the protein to elucidate structural or environmental variations at a local level. Consequently, evaluating the immobilised redox enzyme orientation or observing protein dynamics is difficult as it is hampered by the global response of the protein amide bands. As well, monitoring catalysis at the redox active site is restricted to only a handful of enzymes. To lift off those limitations I propose to edit redox enzymes with site-specific vibrational probes (VPs). In this project, I will combine state of the art SEIRA spectroelectrochemistry to the introduction of site-specific VPs in laccase as a model of redox enzyme. Laccase catalytic activity couples the one electron oxidation of a wide range of organic and inorganic substrates to the four-electron reduction of molecular oxygen into water. We will decipher the orientation – activity relationships of laccase upon immobilisation onto electrodes. We will subsequently monitor its structural dynamics at a localised level and ultimately probe the various states of its catalytic cycle. This project will pave the way for the spectroelectrochemical characterisation of poorly or yet uncharacterised redox enzymes.

The basic research described in this proposal concerns studies in fundamental organic chemistry in the field of organocatalysis. Despite the considerable progresses of the science of organic synthesis and the advent of organocatalysis, general methods to generate chiral “all carbon” quaternary centers with high levels of stereoselectivity are rare, and this synthetic issue remains a challenge. Chiral “all carbon” quaternary centers can be found in spiro bicyclic compounds, a class of molecules with spectacular chemical and conformational properties. We propose to develop a general and flexible stereoselective organocatalytic approach to spiro compounds containing a chiral “all carbon” spiro carbon atom using the reactivity of zwitterionic ketoenolate equivalents mediated by Lewis base catalysts (NHCs and isothioureas). We also propose to develop a new class of organocatalysts for iminium activation with enhanced catalytic activity and stereoselectivity when compared to state of the art organocatalysts. These new organocatalysts have been rationally designed around a conformationally constraint spiro bicyclic core containing a chiral “all carbon” spiro carbon atom, and they may be prepared by the method we propose to develop using the reactivity of zwitterionic ketoenolate equivalents. We anticipate that our designed organocatalysts for iminium activation will allow for unprecedentedly efficient and stereoselective reactions, more specifically for the preparation of molecules with chiral “all carbon” quaternary centers.

The CHLOR2NOU project aims to develop new monitoring tools for CLD and its TPs, to provide new knowledge on the fate and risk of CLD TPs, and to explore realistic alternative approaches for pollution remediation. The postulate of the non-degradability of CLDs commonly admitted for several decades has had a strong negative impact on pollution management by ruling out the possibility of CLD degradation. The representation of CLD in the FWI society and in the scientific community is therefore of paramount importance. The CHLOR2NOU project is divided into 7 Work Packages that bring together scientists from various background: the WP1 with the synthesis of CLD TPs, CLD baits and fluorescent macromolecular cages; the WP2 that deals with innovative analytical methods: (i) routine laboratory method for the detection of CLD TPs in environmental and food matrices, (ii) immunoassay using a CLD-selective antibody, (iii) a semi-high-throughput detection protocol based on the recognition of CLD by a fluorescent macromolecular cage; the WP3 dedicated to toxicological and ecotoxicological studies in order to define the toxicity profile of CLD TPs; the WP4 with several analytical campaigns to obtain a first estimate of the possible exposure to CLD TPs; the WP5 that aims at studying the fate of CLD TPs, in particular in FWI soils, while defining degradation indicators; the WP6 that is focused on the study of realistic agronomic and environmental conditions capable to favor CLD degradation; the last WP centered on the representation of CLD in the FWI society at large. A co-construction method will be used to help the population and stakeholders to better assimilate the scientific results.

In this project, we will develop new chiral transition metal catalysts bearing N-heterocyclic carbene (NHC), cyclic alkyl amino carbenes (CAACs) ligands and other carbene ligands containing a sole axial chirality. In an original and unique manner, the complexes will be prepared from readily available achiral NHC precursors. Thus, the enantiopure complexes will be obtained by preparative chiral HPLC resolution which will provide access to both enantiomers with high optical purity (>99%). The design of the atropisomeric carbenes structures will be supported by DFT calculations which will be performed at an early stage. This project will tackle some fundamental aspects related to chirality including mechanistic aspects of carbene transmetalation, looking to understand the fate of the chiral information during this process. Beyond these fundamental studies, the aim is to create new series of efficient and inexpensive chiral catalysts in order to perform original enantioselective transformations.

The goal of the MultiChiral project is the design of a unified enantioselective strategy combining organocatalysis with conversion of chirality for accessing original molecules featuring multiple stereogenic elements, with a special focus to the challenging control of axial and helical chiralities. The general pathway involves the organocatalytic enantioselective cyclization of simple well-designed achiral precursors into partially saturated cyclic intermediates bearing either central/helical or central/axial chiralities. They will be transformed during an aromatization step that converts the central chirality into the axial chirality, generating molecules with either axial/helical, di-axial, tri-axial or di-axial/helical chirality. The absolute configuration of final products will be characterized using chiroptical spectroscopies and single crystal X-ray diffraction (SCXRD). The second axis of the project will focus on the crystalline state of the heterohelicenes and more specifically on obtaining chiral supramolecular organizations by screening the crystallization conditions. The chiral properties of these materials will be studied in detail using the complementarity of SCXRD, chiroptical spectroscopies and DFT calculations. A very close collaboration between synthetic organic chemists, theoretical chemists, and physical chemists will be required for the success of this project.