Exploiting molecular length as a means of enhancing control and selectivity of anion relay transporters Toby G. Johnson, Amir Sadeghi-Kelishadi, Andrew Docker and Matthew J. Langton University of Oxford, UK In nature, ion transport across cellular membranes is mediated by either mobile carrier ionophores or transmembrane channels. Naturally occurring transporters are highly adapted to selectively bind specific ion and some complex transmembrane proteins are capable of responding to external stimuli to controllably switch transport ON and OFF. To date, most synthetic transporters utilise these same biotic mechanisms of transport, but exceptional new systems based on the motions of molecular machines are being developed. 1,2,3 Our aim is to exploit the unique properties of relay transport, to develop systems which mimic the selectivity and control achieved in nature. Recently we have shown that incorporation of a photoswitchable azobenzene unit into the carrier arm of a relay transporter allows reversible control over transmembrane transport. 4 We demonstrate that visible light can be used to control the rate of ion transport by changing the length of the telescopic carrier arm, and thus the ability to “pass” the ion between transporters anchored on opposite sides of the membrane. Crucially two molecules are required to work cooperatively for the relay transport of ions across the bilayer, where anion exchange was found to be rate limiting. This work suggests that confining ensembles of molecular machines within membranes provides a powerful method to control their relative position and orientation, to access systems in which multiple molecular machine-like components work in concert. The implications of the relay mechanism on the selectivity of ions transported across the bilayer are currently under investigation, to determine if this abiotic mechanism may provide an alternative means of enhancing selectivity. 5 We have synthesised a halogen bonding relay transporter, which displays unprecedented activity and significant selectivity for the transport of Cl - over OH - ions. Enhancing selectivity is of significant interest for the application of synthetic ionophores as future therapeutics and one which relay transporters are demonstrating great promise for. Relay transporters are only just beginning to be explored, but this underinvestigated mechanism is expected to enable major advancements in the field of membrane supramolecular chemistry.
References 1. L. E. Bickerton, † T. G. Johnson, † A. Kerckhoffs † and M. J. Langton, Chem. Sci ., 2021, 12 , 11252-11274. 2. B. A. McNally, E. J. O’Neil, A. Nguyen and B. D. Smith, J. Am. Chem. Soc. , 2008, 130 , 17274-17275. 3. C. Wang, S. Wang, H. Yang, Y. Xiang, X. Wang, C. Bao, L. Zhu, H. Tian and D. H. Qu, Angew. Chemie - Int. Ed. , 2021, 60 , 14836-14840. 4. T. G. Johnson, A. Sadeghi-Kelishadi and M. J. Langton, J. Am. Chem. Soc. , 2022, 144 , 10455-10461. 5. T. G. Johnson, A. Docker and M. J. Langton, Manuscript under preparation .
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