Organic cage catalysts for selective chemical transformations

Chemists remain astounded by the superior selectivity achieved by Nature's biomachines: enzymes. In order to better understand these large protein catalysts, chemists are studying cage-shaped molecules that act as enzyme mimics. These models - smaller than enzymes, but larger than "small molecule catalysts" - are like enzyme "active sites", which perform the key chemical bond making and breaking, and allow us to study in isolation nuanced contributions to enzyme selectivity, such as electric field orientations.

We have recently designed a new class of cage molecule with a carefully functionalised interior that closely mimics a dominant class of enzymes. In this synthetic organic chemistry project, we propose to synthesise and develop these molecular cages as selective catalysts. We will use physical organic chemistry and computational modelling techniques to understand how they function as catalysts, and tie this understanding back to enzymes.

As well as their value as models, we expect these cage molecules to be applied as useful catalysts in their own right. Since they share the 3D scaffolds available to proteins, we will tune the cages to effect transformations not currently possible using solution phase synthetic chemistry. Likewise, since the cages are soluble in organic solvent, we can pursue reactions not feasible for aqueous-based enzymes.

In particular, as part of our goal to further sustainable synthesis, we will explore challenging regioselective transformations of biomolecules relevant to medicinal chemistry, such as lipids.

The project will involve training in a wide-range of synthetic, analytic, and modelling techniques, including supramolecular synthesis and size-exclusion separation methods, kinetic and binding measurements, and DFT and molecular dynamics modelling.