Dynamically Adaptive Metal-organic Nanopores

Lead Research Organisation: University of Cambridge
Department Name: Chemistry


We propose to prepare and study a new class of synthetic ion channels based on dynamic metal-organic complexes that possess a pore-like central channel that will allow for substrate transport across a lipid bilayer.
These complexes are obtained through the condensation of simple organic building blocks around octahedral metal ion templates. The modular nature of these complexes and the dynamic nature of their imine bonds will allow us to tune the assemblies to confer different physical properties upon them, while retaining their overall structures. Through tuning we will identify the key characteristics of complexes that can be inserted into lipid bilayers. This project builds upon preliminary investigations that have shown that heptyl-chain-bearing derivatives allowed chloride ions to pass across a membrane, providing a point of departure for our investigations.
In other key precedent work we established that it is possible to induce reconstitution of the complexes into entirely different structures in the presence of different templating anions. We will investigate ways to exploit this phenomenon as an approach to controlling flux across a membrane by reversibly triggering reconstitution to form complexes that do not possess central channels, thus inhibiting ion transport.
Development of these tuneable, gating ion channels will pave the way to new industrial processes that are driven by the effective separation of high value compounds from impure mixtures, and new chemical transformations involving the selective gating of intermediate species between vesicular reaction chambers. In future, our technologies may also facilitate new treatments for those who suffer from forms of channelopathy.

Planned Impact

Beyond the academic community, the development of new synthetic ion channels in this project will have an impact on industry and the general public.

Industry: A key aim of this project is to develop a methodology for the generation of new types of reconfigurable membrane materials that could address some of the fundamental problems encountered in chemical industry, one of the largest manufacturing industries in the UK. Separations are central to a plethora of industrial processes and the use of membrane technologies that can selectively isolate valuable species from a mixture provides a low energy, high efficiency alternative. Pores and porins play key role in intercellular communication and drug development. Creating artificial gating pores will pave the way to the development of medical technologies that could treat those who suffer from forms of channelopathy.
Intellectual property (IP) will be protected and exploited in accordance with the published policy of the University of Cambridge to the benefit of all individuals and institutions involved. After the protection of any relevant IP, dissemination will be through publication in top international journals and domestic and international presentations. We will make sure that relevant IP is patented, potential licensees are recognised, and that possibilities for launching spin-outs are also properly identified.

General public: Appreciation and public support for scientific progress have underpinned technological progress in the UK ever since the practice of science became professionalised in the 19th century. We are committed to maintaining our side of this dialogue through explaining to the public what we do and why. One mechanism for this is press coverage of our research programme. The Nitschke group's 2009 Science paper generated a dozen stories in newspapers, TV, and radio across more than five countries, all with a positive bent. Another mechanism is structured outreach events; JRN will present his group's research to the 2014 international 'Pint of Science' festival (http://www.pintofscience.com/).

Education: In the context of undergraduate education, one of the Nitschke group's self-assembled systems are highlighted in a first-year undergraduate chemistry textbook (Chemistry: The Molecular Science, 4th ed, C. L. Stanitski, P.C. Jurs, M. Sanger, Brooks/Cole, Stamford CT USA, 2011; p. 1024) and has already been adapted for use in undergraduate practical exercises (at Harvey Mudd College in California).


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Percástegui E (2017) Anion Exchange Renders Hydrophobic Capsules and Cargoes Water-Soluble in Angewandte Chemie

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Percástegui EG (2017) Anion Exchange Renders Hydrophobic Capsules and Cargoes Water-Soluble. in Angewandte Chemie (International ed. in English)

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Plajer AJ (2019) Tailoring the Binding Properties of Phosphazane Anion Receptors and Transporters. in Journal of the American Chemical Society

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Plajer AJ (2020) Conformational Control in Main Group Phosphazane Anion Receptors and Transporters. in Journal of the American Chemical Society

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Ramsay WJ (2016) Subtle Ligand Modification Inverts Guest Binding Hierarchy in M(II)8L6 Supramolecular Cubes. in Journal of the American Chemical Society

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Rizzuto FJ (2016) Peripheral Templation Generates an M(II) 6 L4 Guest-Binding Capsule. in Angewandte Chemie (International ed. in English)

Description Initial results have validated our hypothesis - that metal-organic structures of the sort described in our proposal can indeed selectively gate anions (chloride, bromide) through a membrane, whilst excluding others. We have also seen that the presence of certain anions, such as the soap dodecylsulfate, can block the pores. A key publication has been accepted in the top journal Angewandte Chemie. Another publication is in a late stage of preparation.
Exploitation Route There may be relevance to designing complex chemical systems consisting of membrane-bounded spaces, with channels serving as communication vectors between them. There might even be some relevance to channelopathy diseases - early days!
Sectors Chemicals,Education,Energy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://www-jrn.ch.cam.ac.uk/
Description Keyser collaboration 
Organisation University of Cambridge
Department Department of Physics
Country United Kingdom 
Sector Academic/University 
PI Contribution We have made metal-organic nanopores
Collaborator Contribution They have studied these groups as ion channels in bilayer membranes
Impact Publication: "Blockable Zn10L15 ion channels via subcomponent self-assembly", C.J.E. Haynes, J. Zhu, C. Chimerel, S. Hernández-Ainsa, I.A. Riddell, T.K. Ronson, U.F. Keyser, J.R. Nitschke, Angew. Chem. Int. Ed. 2017, 56, 15388-15392.
Start Year 2012