The main research theme in the Gouverneur laboratory is fluorine chemistry.
1. Innovative Fluorine Chemistry To Understand, Diagnose And Cure Diseases
We have an extensive programme aimed at developing novel synthetic methodologies for the preparation of complex fluorinated molecules designed to understand, diagnose and cure diseases. Specifically, 19F-NMR is a valuable tool in fragment-based drug discovery; its applications include screening libraries of fluorinated fragments, studying competition among fragments, and identifying the binding mode of promising hits. Fluorine-substitution is also highly advantageous in pharmaceutical compounds as its presence can dramatically alter chemical and biological properties, including stability, lipophilicity and bioavailability; a recent survey has estimated that as many as 20% of pharmaceuticals contain fluorine. Finally, 18F-labelled molecules have wide applications in Positron Emission Tomography (PET), a molecular imaging technology routinely used in the clinic for diagnosis, and in research laboratories to inform drug development programmes. As natural fluoro-organic compounds are extremely rare, major advances rely heavily on synthetic organic chemistry. Our programme on late stage fluorination aims at enhancing our fundamental understanding of fluoride reactivity, populating the toolbox of reactions available for the synthesis of fluorine-substituted molecules including peptides and proteins, transforming the field of 18F-radiochemistry, and allowing access to 18F-labeled radiotracers enabling PET for diagnostic and drug discovery. Over the years, our research program has closed the gap in innovation between 19F-chemistry and 18F-radiochemistry, with the design of more than forty fluorination reactions including fifteen 18F-radiofluorination processes. Some of our methods are routinely employed to access 18F-radiotracers for PET applications. Our radiochemistry laboratory grew to become a high-in-demand facility for radiotracers production in Oxford. For example, 18F-Olaparib, a new radiotracer prepared applying radiochemistry developed in the group, is taken up for clinical studies. 18F-Olaparib can be used to visualise the biological effects of radiotherapy in cancer patients, determine if the dose of irradiation given to a patient is sufficient to kill the tumour, or if changes are to be made to the therapy plan.
2. Cost-effective Fluorine Chemistry and Bringing Solutions towards Circular Economy
Sustainable chemistry is a necessity that provides great opportunities for the fluorochemical sector. Circular solutions such as fluorochemical recycling or repurposing will have an overall positive impact on the environment over their full life cycle. This research theme requires innovative solutions to challenging problems including harnessing fluoride reactivity, or recycling/repurposing fluorinated polymers and other bulk fluorine-containing materials produced at an industrial scale. A recent research highlight includes the development of a new class of bio-inspired urea organocatalysts for enantioselective fluorination with metal alkali fluoride such as KF and CsF, the safest and most cost-effective fluorine source. These catalysts are now commercially available.
