Active Trans-Membrane Transport through Transition Metal Catalysed Iterative C-H Functionalisation (May Change)

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Autonomous chemically-fuelled directional motion underpins the function of many of nature's magnificent biological motor proteins. Mimicking or replicating such behaviour in artificial small molecule systems is a hugely exciting challenge. Numerous artificial systems have been developed which allow the passive transport of molecular cargo across lipid bilayers.1 However, systems which exhibit active transport are much less well developed. The aim of this project is to use a recently developed novel methodology, involving iterative functionalisation of hydrophobic molecular tracks to create a system capable of actively transporting molecular cargo across a protocell membrane.By exploiting two processes reported in the literature, it has been possible to achieve rhodium catalysed iterative C-H functionalisation of biphenyl, and terphenyl, boronic acid tracks. This process combines-for the first time-transition metal-catalysed directing group-assisted C-H functionalisation with [1,n] transition metal migrations. Finding a methodology to efficiently synthesise longer polyphenyl boronic acid tracks will be a key starting point for this project. Investigation and optimisation of the rhodium catalysed iterative C-H functionalisation of these longer tracks will follow. This project will also involve the development of new transition-metal catalysed iterative functionalisation methodologies.Exploiting the Gobbo group's extensive expertise in the development and investigation of synthetic protocells, we propose that the hydrophobic molecular tracks could be inserted across a protocell membrane to achieve active transport of molecular cargo under chemically-fuelled conditions.In biological systems, transport across membranes often represents a crucial step in complex chemical cascades or signalling pathways. In this project, such sophisticated chemical networks will be used as inspiration for the development of novel synthetic cells with transition metal catalyst-mediated chemical signalling properties.1) S. Chen, Y. Wang, T. Nie, C. Bao, C. Wang, T. Xu, Q. Lin, D. H. Qu, X. Gong, Y. Yang, L. Zhu and H. Tian, J. Am. Chem. Soc., 2018, 140, 17992-17998.2) M. Lautens, W. Klute, W. Tam, L. F. Tietze, A. Padwa, M. D. Weingarten, D. F. Harvey, D. M. Sigano, M. Malacria, E. Negishi, C. Copéret, S. Ma, S.-Y. Liou, F. Liu, T. Satoh, Y. Kawamura, M. Miura, M. Nomura, M. Catellani, L. Ferioli, F. Cugini, G. J. Bocelli, R. C. Larock and P. L. Johnson, Angew. Chem., Int. Ed. Engl, 1996, 96, 42. 3) S. Ma and Z. Gu, Angew. Chemie Int. Ed., 2005, 44, 7512-7517.