Stimulus Responsive Coordination Chemistry within Lipid Bilayers

We are developing responsive supramolecular systems that can be embedded into the membrane of artificial (or living) cellular compartments and used as chemical tools to control a range of different functions, including transduction and amplification of chemical signals, catalysis of reactions at the bilayer interface and transport of molecular cargo across the membrane.

We are interested in developing stimuli-responsive ionophores, in which application of an external trigger (light, redox, enzymes) is used to switch on ion transport across a membrane. For example, we have developed light activated anion transporters that operate via a new concept of photo-regulated carrier mobility, in which photo-cleavage of an anchoring group which inhibits mobility can be used to activate chloride transport (see figure left). Notably, this approach does not involve the direct functionalisation of the ion binding site and thus can be applied to a wide range of ionophores without de novo design of the binding site (Chem. Sci., 2022). We have also developed a post-synthetic modification strategy to access a range of multi-stimuli responsive ionophores that operate via a hydrogen bond switch mechanism, in an unprecedented AND logic gated responsive ionophore system (Angew. Chem. Int. Ed., 2024)

We have expanded the concept of facilitated ion transport to that of catalytic ions, reporting the first example of a transport system for Pd(II) cations, which when delivered across a membrane, trigger a catalytic transformation inside vesicles. The system could also be made photo-responsive by incorporation of a suitable photocage, thus enabling light activated transport-coupled catalysis in artificial cells (JACS, 2023).

In addition, we have used a similar approach to demonstrate the first example of an artificial inter-vesicle signalling network (Angew. Chem. Int. Ed., 2023). By utilising photo-caged cationophores bound to the membrane of vesicles, a signalling system could be developed in which photo-irradiation triggers their release from the "sender" vesicles. Uptake into a larger population of "receiver" vesicles leads to turn-on of ion transport in this remote population, and amplification of the signal (see figure below). These approaches - using relatively simple synthetic components – have the potential to open up new avenues for engineering complex signalling networks and controlling catalytic reactions such as for biomolecular decaging or in-cell synthesis within both artificial and living cells.