Final Report Summary - TRANSPORET (Transmembrane Molecular Machines)
We have successfully adopted a physical organic chemistry approach to understanding and exploiting molecular interactions and chemical reactivity to construct and observe the non-equilibrium operation of molecular machines and supramolecular devices. We have developed DNA-based devices that exploit base-pairing interactions to perform fundamental computational logic operations, and examined the nanomechanical transport of DNA through protein nanopores. We have developed and shown the operation of one of the earliest transmembrane molecular machines built from a combination of synthetic and biological molecules. This device was shown to be capable of converting chemical fuels into nanomechanical motion across a membrane. Moving beyond a purely supramolecular approach to assembling molecular machines, we have developed new methods for introducing synthetic modifications into biological transmembrane proteins; an advancement that will pave the way to hybrid synthetic/biological transmembrane machines such as molecular-scale pumps. While developing this modification chemistry, we uncovered the ability to interrogate reaction mechanisms on the single-molecule level. Moreover, we have found that we are able to exploit the non-equilibrium application of an electric field to determine the charge state, and therefore identity of particular intermediates along single-molecule reaction pathways. In collaboration with the Lusby group (Edinburgh), we have used transmembrane signals to recognise the chirality, catalytic, non-covalent binding properties of metal complexes in electric fields. In collaboration with Webb (Manchester) and Clayden (Bristol) we have examined synthetic transmembrane signalling molecules and pore-forming molecules. Finally, we have worked with Hofkens (KU Leuven) and Feringa (Groningen) groups to develop methods of simultaneously observing and analysing the single-molecule operation of molecular machines at interfaces.