RS Fellow - EPSRC grant (2016): Realising the Automated Materials Synthesiser

Lead Research Organisation: University of Liverpool
Department Name: Chemistry

Abstract

High throughput screening (HTS) is an 'accelerated serendipity' approach to find breakthroughs in materials faster by carrying out large numbers of experiments in parallel batches. However, if new materials are to be useful, they must be scalable, cheap, and reproducible. This is a major stumbling block, as batch conditions can be hard to scale up at reasonable cost: it is often difficult to get from the 'hit' on the screening robot to a large scale product. Continuous flow chemistry holds untapped potential to solve these issues by reducing reaction times, increasing yield, and simplifying scale up with excellent reproducibility. The focus of this project is to merge the fields of flow chemistry and materials science to bring new high-performance materials to market. By focusing initially on supramolecular materials - that is, materials made of discrete molecules, not extended frameworks -self-assembly and crystallisation will be controlled in flow, tailoring the properties of the resultant materials. A strong theme of the project will be the integration of algorithms and analysis to automatically optimise flow synthesis, coupling synthesis, purification, analysis, and automation.

Planned Impact

Please refer to attached Royal Society application.
 
Description During this grant, we have developed a number of strategies to control the yield and selectivity of chemical reactions relevant to supramolecular chemistry. We use molecular design, continuous flow chemistry, and crystallisation approaches to target the controlled formation of macrocycles, cages, and other organic molecules with applications in fields such as separation, pollution remediation, and potentially in medicinal/drug delivery applications. We seek to automate these processes and are making progress towards a fully autonomous system for discovery, optimisation, and scale up of these compounds.

In 2021 we published "High-Yielding Flow Synthesis of a Macrocyclic Molecular Hinge". This work used at-line UPLC-MS analysis to optimise the semi-continuous synthesis of a macrocyclic species via novel covalent chemistry. By performing the synthesis in a flow reactor with two heated coils, we were able to ensure a high mixing rate and automate reagent additions at fixed time points. Use of a dynamic backpressure regulator (BPR) allowed the reaction temperature to be safely increased up to 100°C. Furthermore, a switching valve enabled automatic sampling of the reaction mixture for analysis by ultra-performance liquid chromatography mass spectrometry (UPLC-MS). These at-line measurements provided additional insight into the reaction mechanism by allowing intermediates and side products to be rapidly detected. This study showcases our ability to rapidly assess and optimise irreversible reactions in flow using real-time data.

In 2020 we published "Inducing social self-sorting in organic cages to tune the shape of the internal cavity". This work exemplifies our strategy to control molecular shape via the design of building blocks and exploiting self-sorting under equilibrium conditions. This work was carried out in batch and with very limited process control (i.e. no optimisation of conditions) yet discovered a non-linear building block motif that could reliably form low-symmetry cages when paired with linear precursors and reacted with diamine partners. In the course of this study at least fourteen new cages were detected, many with unique geometry and topology, but only 7 could be isolated, 3 of which had low symmetry. We are building on this study with our flow optimisation approaches.

The platforms developed in the course of these studies are being rapidly built on within our group and applied to a range of chemical processes and problems. As a result of this work, we are also working with industrial partners to develop their batch reactions in flow, aiming to achieve lower energy processes, reduction of waste production, and higher yields and selectivities.
Exploitation Route Researchers working in supramolecular chemistry will benefit from the flow methods we have detailed; we are already working with new collaborators to implement our strategies in new areas and to deliver benefits in scale, reaction speed, yield, and selectivity of challenging supramolecular substrates. We are also working with industrial partners to implement our optimisation strategies to large-scale batch processes.
Sectors Chemicals,Manufacturing, including Industrial Biotechology
 
Description This award was a 'first grant' scheme assessed and administered by the Royal Society, and subsequently funded via the EPSRC as it was identified as being relevant to their portfolio. As such, it is an unusual award that was foundational to setting up our research lab but did not necessarily have direct traceable impacts planned beyond academia. COVID also significantly affected this award, making links to impact somewhat challenging to define. However, it was pivotal to building our research in using continuous flow methods for enhanced control of chemical processes, and as such all subsequent work I have done could be seen as a direct consequence of this award. This dichotomy makes it a little difficult to fill out the ResearchFish form! For example, we now have partnerships with industry that will potentially lead to huge benefits in terms of reduced waste and energy use for processes used on an enormous scale - work here is early stage and thus not included in reporting. Over the coming years, I expect to significantly develop our evidence of wider impact in terms of economic and societal benefits.
Sector Chemicals
 
Description Industrial funding
Amount £268,063 (GBP)
Organisation Victrex 
Sector Private
Country United Kingdom
Start 08/2022 
End 09/2024
 
Description University Research Fellowships
Amount £978,774 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2021 
End 12/2025