Next generation ruthenium catalysts for asymmetric C-H functionalization

Nature uses a standard alphabet of 20 amino acids, specified by the genetic code, to create enzymes capable of catalyzing a diverse array of complex transformations. As a consequence, our existing enzyme production and engineering strategies rely exclusively on these natural amino acid building blocks, which contain limited functionality and are not suitable for the creation of artificial enzymes with truly novel activities.

Within this project, we will exploit state-of-the-art techniques in protein engineering to install 'chemically programmed' ligands capable of binding a ruthenium co-factor into existing enzyme scaffolds, in order to create artificial enzymes for selective 'catalyst controlled' functionalizations of unactivated C-H bonds. This strategy combines the benefits of small molecule- and enzyme- catalysis by allowing optimization of the local co-ordination environment surrounding the catalytic centre whilst maintaining the tuneable protein environment required for selective substrate orientation and stabilization reactive intermediates.

This project brings together chemo and biocatalysis to deliver a step change in the development of tools that can be used for the selective C-H functionalization of aromatic molecules. By nature, these new tools will be compatible with polar functionalities typically present in biologically active molecules, thus ensuring applicability to 'real world' molecules, rather than just simple model substrates.