The Oxford Science Lecture Series, part of the Oxford International Women’s Festival
Professor Veronique Gouverneur Ph.D., Chemistry Research Laboratory, University of Oxford
“Fabulous Fluorine”, Dorothy Hodgkin Memorial Lecture 2018, University Museum, Oxford, 6th March 2018
The Oxford Association for Women in Science and Engineering (AWiSE) is a support network for women in science and technology as well as reaching out into the wider community to show that women can do science successfully and with great enjoyment.
The 2018 Dorothy Hodgkin Lecture was given by Professor Gouverneur, Professor of Chemistry at the University of Oxford. She obtained a Masters and her doctorate in chemistry from the University of Louvain. She worked at the Scripps Research Institute for two years before taking up a post at the Louis Pasteur Institute in France. She joined the Chemistry department in Oxford in 1994 and became a Professor in 2008. She described how she had always wanted to be a chemist, to learn how to make molecules and to improve their function. Her mother was a primary school teacher and her father a chemical engineer who subsequently became a diplomat. Although she spent time at the Scripps, Professor Gouverneur declined an Associate Professorship there in order to return to Europe. She knew from early on that she wanted to be an academic research chemist but it took her two to three years to realise that she wanted to work with fluorine.
Professor Gouverneur began her lecture by talking about Dorothy Hodgkin and her passion for archaeology, commenting that it showed Dorothy’s love of pattern, as evident by her skill in interpreting protein crystallography patterns. When Dorothy deduced the structure of penicillin it was at a time when there was immense competition to find the answer. If you know the structure of a drug it helps with the design of the synthesis but also means you can design analogues and optimise the delivery and therapeutic effect of the drug as structurally related compounds may be more potent or more easily absorbed by the body. Out of 4000 natural halogenated compounds, only ten contain fluorine. So why doesn’t nature like fluorine? The earth’s crust and the sea both contain fluorine, but it is very rare in biology. Nature uses haloperoxidases and hydrogen peroxide to attach chlorine to molecules and can oxidise chlorine, bromine and iodine, but not fluorine. Despite this problem with fluorine in nature, 20-25% of drugs, 30-40% of agrochemicals and many, many polymers contain fluorine. For example, Prozac contains a CF3 group which changes the pharmokinetics and helps the molecule to be lipophilic so that it can cross the blood-brain barrier.
In contrast, there are many ways to add fluorine to a molecule in the lab, which is a ‘playground of reactivity’. Professor Gouverneur said that to synthesize a drug you should start with a small fluorinated compound and build up from there. It is more problematical if you start with a lead compound as you need to add fluorine in a range of sites which can be very labour intensive. In Oxford, she developed a new type of chemistry which can add fluorine to a molecule in multiple places. She said that synthesis of vitamin B12 took over 100 post-doctoral researchers, it is a much easier to have a site-selective technique to change a C-H bond to a C-F or C-CF3 bond. This technique has resulted in a large number of collaborations with the Pharmaceutical Industry to develop drugs that had previously been hard to synthesize.
Having broken ground in fluorine chemistry, in 2001 Professor Gouverneur realised that lots of research groups were now working in that field and so she looked for a new area of research to make her own. She decided to try to do chemistry with the unstable fluorine isotope 18F which is prepared in a cyclotron and useful for Positron Emission Tomography (PET). A PET scan using an 18F analogue of glucose shows regions of tissue with high glucose metabolism, such as tumours, and so can show whether a treatment regimen is reducing the tumour size………….
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