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

自主的化学燃料定向运动支撑着许多大自然伟大的生物运动蛋白的功能。在人工小分子系统中模仿或复制这种行为是一项非常令人兴奋的挑战。已经开发了许多人工系统，使分子货物能够通过脂质双分子层被动运输然而，表现出主动运输的系统则不太发达。该项目的目的是使用最近开发的新方法，涉及疏水分子轨道的迭代功能化，以创建一个能够主动运输分子货物穿过原细胞膜的系统。通过利用文献中报道的两个过程，可以实现铑催化的联苯和三苯硼酸轨道的迭代C-H功能化。这一过程首次结合了过渡金属催化的定向基团辅助的C-H功能化和过渡金属的[1，n]迁移。寻找一种方法来有效地合成较长的多苯基硼酸轨道将是这个项目的关键起点。研究和优化铑催化的迭代C-H功能化这些较长的轨道将遵循。该项目还将涉及开发新的过渡金属催化迭代功能化方法。利用Gobbo团队在合成原始细胞的开发和研究方面的广泛专业知识，我们提出可以将疏水分子轨道插入原始细胞膜，以在化学燃料条件下实现分子货物的主动运输。在生物系统中，跨膜运输通常是复杂化学级联反应或信号通路的关键步骤。在这个项目中，这种复杂的化学网络将被用作开发具有过渡金属催化剂介导的化学信号特性的新型合成细胞的灵感。1)陈思生，聂涛，聂涛，王超，徐涛，林清，曲德华，龚晓燕，杨艳，朱丽，田慧，安俊。化学。Soc。中国机械工程，2018,14(1)，刘建军，刘建军，刘建军，刘建军，刘建军，刘建军，刘建军。Liou， F. Liu， T. Satoh， Y. Kawamura， M. Miura， M. Nomura， M. Catellani， L. Ferioli， F. Cugini， G. J. Bocelli， R. C. Larock和P. L. Johnson, Angew。化学。, Int。英语教育，1996,96,42。(3)马淑娟、顾志强。化学Int。编辑，2005,44,7512-7517。

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.