Enzymes are the ultimate enablers of precise chemical transformations. Until recently, chemists have not had the synthetic tools to efficiently assemble 3D scaffolds such as those found in enzymes – let alone the ‘active site’, which performs the key chemistry. My research seeks to utilise supramolecular self-assembly to rapidly access tunable 3D cage scaffolds. The challenge is to then desymmetrise these geometric scaffolds to generate specific 3D environments such as those found in enzymes. The developed synthetic cage structures will be tuned for molecular-sensing and catalysis applications, specifically those requiring a level of atomic precision and pre-organisation currently beyond the reach of small molecule tools.
Robust, Soluble Organic Cages
Chemical self-assembly typically requires rigid, geometrically-matched building blocks able to undergo “self-healing” (reversible bonding) to access closed (rather than oligomeric or lattice-like) structures. Due to these constraints, the resulting structures are often highly symmetric and poorly soluble. My research seeks to develop highly soluble organic cages and methods for their desymmetrisation. The soluble cages have functional handles both inside the cavity and around the periphery, and display fascinating enzyme-like behaviour – chemical reactivity that arises from the precise arrangement of the residues around the cavity. The tunability of these cages means that, in principle, libraries of enzyme-like cavities can be synthesised. This approach, if successful, will allow goal-oriented molecular sensing (for example, using dynamic covalent combinatorial chemistry to design hosts for specific guests), and even control of substrate access to reactive cavities to mimic enzyme-like specificity.