Fluorinations with implications: enhancing the potential of biologically and medicinally interesting molecules through targeted fluorine introduction

The process of developing bioactive compounds into drugs is notoriously difficult, costing the pharmaceutical industry years and billions of dollars per drug. The motivation of our research programme is to develop methodologies to improve and accelerate such efforts. The application encompasses three projects, all focused on improving physical properties of bioactive compounds. It is indeed only a recent but very firm realisation that physical properties are as important as bioactivity for a given compound to make it as a drug.
One of these, lipophilicity, a measure for the ease with which molecules enter cells, has proven to be a crucial parameter in drug development: no matter how bioactive the molecule, if it cannot enter cells it is unlikely going to cure disease. One project regards carbohydrates, which are extremely important biomolecules, but have very undesired physical properties. We aim to investigate fundamental aspects of the relationship of carbohydrate structure and lipophilicity and hydrogen bonding (the most important way molecules interact with proteins) to be able to improve carbohydrate properties. A second project aims at refining the very interpretation of lipophilicity, by disentangling the individual contributions of different forms of a molecule. The third project is focused on the shape of molecules: we propose a novel way to control how peptide chains fold. All projects involve “precision fluorination” of molecules aimed at modifying properties.