Multinuclear High-Resolution Flow NMR for In-Operando Investigation & Self-Optimisation of Chemical Reactions
Lead Research Organisation:
University of Bath
Department Name: Chemistry
Abstract
The importance of catalysis for the chemical industry is still increasing with the need to generate new materials in an increasingly sustainable matter. Catalysts are currently designed and optimised with multiple techniques used separately at the end of a reaction, which often leads to long development times. Nuclear Magnetic Resonance (NMR) is frequently used during the chemical development process due to its easy use, high information content and inherently quantitative nature. Recently, FlowNMR systems have been developed where, as opposed to a static solution being placed in a spectrometer, a solution can be flowed through the magnet. This has been shown to quickly provide data not achievable from traditional NMR methods with no perturbation of the reaction system.
After success with FlowNMR for organic and homogenous transition metal catalysed reactions, continuation of reaction monitoring will take place for more complex organic molecules, transition metal complexes and other multinuclear complexes. With this, expansion of fundamental knowledge of the system, including the effect of flow conditions, will be investigated to ensure that meaningful results are achieved. Exploration of the usefulness of the technique will also take place, extending FlowNMR to other types of reactions which are particularly tedious to monitor by conventional techniques such as photochemistry and electrochemistry.
FlowNMR has already shown to aid understanding of catalyst activation/de-activation mechanisms, identification of multiple states in the catalytic cycle alongside providing improved kinetic data. Currently there is not one readily available technique that can be used as universally during reaction development. With improved understanding of catalytic cycles in the early stages of development, there is potential to speed up chemical development across many sectors in both academia and industrial R&D. Without the need to use multiple laborious techniques for characterisation, and the consequential shorter time frames, there is potential to save both time and money with FlowNMR.
Although a wide range of compounds are NMR active, it would be advantageous to devise complementary techniques that may be coupled with FlowNMR to achieve comprehensive reaction monitoring. For this purpose, we will look into the possibility of developing FlowEPR to detect, characterise and quantify paramagnetic species in real time that would otherwise go undetected by FlowNMR alone. This, and coupling with other techniques including real-time mass spectrometry, UV-vis spectroscopy and high-performance liquid chromatography will be pursued within Bath's new Reaction Monitoring Facility.
Finally, together with our industrial partner AstraZeneca we will explore the possibility of using real-time reaction progress data derived from FlowNMR and/or FlowEPR to self-regulate and self-optimise continuous flow systems using appropriate algorithms.
After success with FlowNMR for organic and homogenous transition metal catalysed reactions, continuation of reaction monitoring will take place for more complex organic molecules, transition metal complexes and other multinuclear complexes. With this, expansion of fundamental knowledge of the system, including the effect of flow conditions, will be investigated to ensure that meaningful results are achieved. Exploration of the usefulness of the technique will also take place, extending FlowNMR to other types of reactions which are particularly tedious to monitor by conventional techniques such as photochemistry and electrochemistry.
FlowNMR has already shown to aid understanding of catalyst activation/de-activation mechanisms, identification of multiple states in the catalytic cycle alongside providing improved kinetic data. Currently there is not one readily available technique that can be used as universally during reaction development. With improved understanding of catalytic cycles in the early stages of development, there is potential to speed up chemical development across many sectors in both academia and industrial R&D. Without the need to use multiple laborious techniques for characterisation, and the consequential shorter time frames, there is potential to save both time and money with FlowNMR.
Although a wide range of compounds are NMR active, it would be advantageous to devise complementary techniques that may be coupled with FlowNMR to achieve comprehensive reaction monitoring. For this purpose, we will look into the possibility of developing FlowEPR to detect, characterise and quantify paramagnetic species in real time that would otherwise go undetected by FlowNMR alone. This, and coupling with other techniques including real-time mass spectrometry, UV-vis spectroscopy and high-performance liquid chromatography will be pursued within Bath's new Reaction Monitoring Facility.
Finally, together with our industrial partner AstraZeneca we will explore the possibility of using real-time reaction progress data derived from FlowNMR and/or FlowEPR to self-regulate and self-optimise continuous flow systems using appropriate algorithms.
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
EP/N509589/1 | 01/10/2016 | 30/09/2021 | |||
1792470 | Studentship | EP/N509589/1 | 01/10/2016 | 30/06/2020 | Rachael Broomfield-Tagg |
Description | During this award, a few key findings have been found. Firstly, FlowNMR has been used on a photocatalytic reaction (one that requires light) to gain understanding into how the reaction works and can happen to cause poor reactivity. Currently there are few ways of monitoring photochemical reactions where information gathered is realistic to reaction conditions and not altered by the way it is looked at. Secondly, method development has been completed to allow bi-phasic (2 phase liquid-liquid reactions) to be monitored in real-time using FlowNMR. Again, there are few methods to do this which either cannot give the amount of data collected using our set-up but also unaffected by the way it is monitored. More methods have been developed to allow more NMR active nuclei to monitor via FlowNMR and broaden the number of useful handles we have on a reaction. Each experiment type tested has been optimised to get as much signal as possible, in a very short period of time, to reduce the chance small concentration species are not seen and that data is quantitative. Lastly, these methods have been used to get a better understanding of a Suzuki-Miyaura cross coupling reaction - used heavily in both industry and academia. |
Exploitation Route | The methods developed to monitor reactions using FlowNMR can be used by future students and external users at the EPSRC funded DReaM Facility specifically for reaction monitoring and many are already being used. Knowledge of the Suzuki-Miyaura reaction can be used by those who require carbon-carbon bonds to be formed during their synthetic pathways and are developing new ways of doing this. |
Sectors | Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Description | Scholarship to attend SMASH 2019 conference provided by the conference in collaboration with the RSC NMR Discussion group. |
Amount | $500 (USD) |
Organisation | Royal Society of Chemistry |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2019 |
End | 09/2019 |
Description | Assistant at University of Bath Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Undergraduate students |
Results and Impact | I worked at an open day for the University of Bath. This involved explaining some of the research areas that we cover at the University as well as asking questions on the university itself. |
Year(s) Of Engagement Activity | 2018 |
Description | Pint of Science speaker - Comedy night |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Pint of Science is an international company that has local groups organising lectures and talks for the general public. I was asked to give a 10-15 minute stand-up set on a science topic of my choice where I discussed NMR, reaction monitoring and more specifically - on-line monitoring. This helped the general public get a better idea of these techniques used every day by scientists and the cutting edge technology that is just becoming more frequently used. |
Year(s) Of Engagement Activity | 2019 |
URL | https://pintofscience.co.uk/event/science-comedy |
Description | Presentation at AstraZeneca PhD Day |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Gave a presentation on 'On-line Monitoring of a Suzuki-Miyaura Cross Coupling using Multi-Nuclear FlowNMR' to a range of audience members from industry and academia. This gave insight into methods and the information generated from them. |
Year(s) Of Engagement Activity | 2019 |
Description | Presentation at University of Bath Bolland Symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Presented at 15 minute talk on 'On-line Monitoring of a Suzuki-Miyaura Cross Coupling by Multinuclear FlowNMR Spectroscopy' to collegues in the Chemistry Department. |
Year(s) Of Engagement Activity | 2019 |
Description | Stand up comedian - University of Bath's Minerva Lectures - Science Showoff |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | I was asked to do a 10 minute stand up set as part of the University of Bath's Minerva Lecture series. I gave a comedic set talking about what it is like to be a PhD student, woman in science and research in general. Providing this information in a comedic format hopefully helped show that scientists are 'normal people' and approachable and helped reduce the gap between 'them' and 'us' often seen in the media. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.bath.ac.uk/events/science-showoff/ |
Description | Talk at AZ Case symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Gave a talk at for an AstraZeneca CASE student symposium on 'On-line monitoring of a Suzuki-Miyaura Cross Coupling by Multinuclear FlowNMR Spectroscopy'. This showed the methods and some information gathered to a range of audience members in academia and industry. |
Year(s) Of Engagement Activity | 2019 |
Description | Three Minute Thesis Finalist |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | The University of Bath have a yearly Three Minute Thesis competition where the final involves a talk for the general public at Bath Royal Literary and Scientific Institution. I placed as a finalist and gave a talk explaining my research in under three minutes. This covered aspects including how we monitor reactions and why we need to do this. It brought attention to the topic to a wider range of people in an easy to understand way. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.bath.ac.uk/announcements/three-minute-thesis-3mt-final-2018/ |