Electrochemical generation of oxygen and nitrogen centred radicals
Lead Research Organisation:
University of Greenwich
Department Name: Pharm., Chem. & Environmental Sci., FES
Abstract
The need to design libraries of compounds is essential across a wide diversity of fields such as drug design, new material development or environmental chemistry.
Radical chemistry is a unique tool for achieving this goal, via the construction of complex molecular scaffolds under mild conditions, due to the broad array of radical transformation available. Yet one of the major issues remains the generation of those radicals, which very often require the use of toxic metals or unstable and hazardous compounds. For instance, such conditions are incompatible with pharmaceutical applications, where the product has to be produced safely on a large scale and without any trace of toxic contaminant.
Electrosynthesis is a powerful tool in organic chemistry that circumvents the afore-mentioned issues by allowing the generation of radicals under mild and green conditions. Even though a plethora of transformations have been developed and many of them have been successfully used in several industrial processes, the potential of preparative organic electrochemistry remains largely underestimated. The growing impetus to look for greener and cheaper alternatives to classic synthetic methodologies has further prompted us to investigate new electrochemical methodologies.
Based on very encouraging preliminary results, we envision using electrochemistry to develop a novel way to generate aroyloxy/acryloyl (RCOO*) and amidyl radicals (R2N*) under mild, green, economical and safe conditions.
The project proposed is interdisciplinary since, besides the extensive organic synthetic studies, a comprehensive electroanalytical study using high-speed voltammetry will be performed in order to study the electrode mechanisms and establish the mechanism of the reaction.
Finally, as a proof of concept, the newly developed synthetic methodologies will be used to generate libraries of bioactive compounds (phthalides, isochromanones, isoindolinones, etc. ). This will lay the ground for future medicinal chemistry grant proposals.
Through this research, we will work in close collaboration with IKA which recently released "Electrasyn 2.0", the first commercial electrosynthesis setup. This proposal will lead to constructive feedback that will be shared with IKA in order to develop new applications for Electrasyn 2.0. to further aid research in this area.
Radical chemistry is a unique tool for achieving this goal, via the construction of complex molecular scaffolds under mild conditions, due to the broad array of radical transformation available. Yet one of the major issues remains the generation of those radicals, which very often require the use of toxic metals or unstable and hazardous compounds. For instance, such conditions are incompatible with pharmaceutical applications, where the product has to be produced safely on a large scale and without any trace of toxic contaminant.
Electrosynthesis is a powerful tool in organic chemistry that circumvents the afore-mentioned issues by allowing the generation of radicals under mild and green conditions. Even though a plethora of transformations have been developed and many of them have been successfully used in several industrial processes, the potential of preparative organic electrochemistry remains largely underestimated. The growing impetus to look for greener and cheaper alternatives to classic synthetic methodologies has further prompted us to investigate new electrochemical methodologies.
Based on very encouraging preliminary results, we envision using electrochemistry to develop a novel way to generate aroyloxy/acryloyl (RCOO*) and amidyl radicals (R2N*) under mild, green, economical and safe conditions.
The project proposed is interdisciplinary since, besides the extensive organic synthetic studies, a comprehensive electroanalytical study using high-speed voltammetry will be performed in order to study the electrode mechanisms and establish the mechanism of the reaction.
Finally, as a proof of concept, the newly developed synthetic methodologies will be used to generate libraries of bioactive compounds (phthalides, isochromanones, isoindolinones, etc. ). This will lay the ground for future medicinal chemistry grant proposals.
Through this research, we will work in close collaboration with IKA which recently released "Electrasyn 2.0", the first commercial electrosynthesis setup. This proposal will lead to constructive feedback that will be shared with IKA in order to develop new applications for Electrasyn 2.0. to further aid research in this area.
Planned Impact
Academic Impact:
- New synthetic tools will be shared with the scientific community allowing researchers to prepare new molecules in a more efficient, green, cheap, safe and rapid manner and thereby speeding up their research.
- The research will lead to an increase in the PI's research output and help to establish him as an expert in organic electrochemistry.
- The research will increase the UK's academic presence by training high-quality PhD students and PDRAs.
Societal Impact:
- The new electrochemical methodologies are environmentally friendly. The source of electricity can ultimately be provided by sustainable sources such as wind, solar, or hydro, or even by nuclear reactors. The research will, therefore, take part in an effort to reduce our ecological impact.
- The pharmaceutical industry will benefit from this research. The new synthetic tools developed through this research will increase the speed at which libraries of new bioactive molecules are prepared and therefore speed up the discovery of new drugs.
- Throughout the project, we will seek to develop academic-industry collaborations with a view to future applications of the reaction mechanism being investigated. In the longer term, through commercialisation, we expect our research to have positive impacts on the environment as well as on the overall quality of life and health of society.
Economic Impact:
- The research will lead to a decrease in our ecological impact and therefore decrease the amount of the economic loss associated with our ecological footprint.
- By helping the field of medical research to discover and develop more efficient and cheaper drugs in a faster way, this research will decrease the financial burden of cancer and other diseases on society.
- The research is expected to lead to commercially relevant results.
People:
- This research will develop the careers of the PDRA and PhD student involved, enhancing their capacity to become highly qualified multidisciplinary independent researchers.
Knowledge:
- The newly developed methodologies will be shared with the academic and industrial community at large through peer-reviewed articles, articles in open-source repository, presentations at national and international conferences and through social media.
- The interdisciplinarity of the research will lead to some high-impact articles with authors publishing in domains and journals not usually used by them, thereby extending the reach of the knowledge exchange.
- New synthetic tools will be shared with the scientific community allowing researchers to prepare new molecules in a more efficient, green, cheap, safe and rapid manner and thereby speeding up their research.
- The research will lead to an increase in the PI's research output and help to establish him as an expert in organic electrochemistry.
- The research will increase the UK's academic presence by training high-quality PhD students and PDRAs.
Societal Impact:
- The new electrochemical methodologies are environmentally friendly. The source of electricity can ultimately be provided by sustainable sources such as wind, solar, or hydro, or even by nuclear reactors. The research will, therefore, take part in an effort to reduce our ecological impact.
- The pharmaceutical industry will benefit from this research. The new synthetic tools developed through this research will increase the speed at which libraries of new bioactive molecules are prepared and therefore speed up the discovery of new drugs.
- Throughout the project, we will seek to develop academic-industry collaborations with a view to future applications of the reaction mechanism being investigated. In the longer term, through commercialisation, we expect our research to have positive impacts on the environment as well as on the overall quality of life and health of society.
Economic Impact:
- The research will lead to a decrease in our ecological impact and therefore decrease the amount of the economic loss associated with our ecological footprint.
- By helping the field of medical research to discover and develop more efficient and cheaper drugs in a faster way, this research will decrease the financial burden of cancer and other diseases on society.
- The research is expected to lead to commercially relevant results.
People:
- This research will develop the careers of the PDRA and PhD student involved, enhancing their capacity to become highly qualified multidisciplinary independent researchers.
Knowledge:
- The newly developed methodologies will be shared with the academic and industrial community at large through peer-reviewed articles, articles in open-source repository, presentations at national and international conferences and through social media.
- The interdisciplinarity of the research will lead to some high-impact articles with authors publishing in domains and journals not usually used by them, thereby extending the reach of the knowledge exchange.
Organisations
- University of Greenwich (Lead Research Organisation)
- Institute of Chemical Technology (ICT) (Collaboration)
- University College London (Collaboration)
- University of Manchester (Collaboration)
- Indian Institute Of Science Education & Research (Collaboration)
- Indian Institute of Science Education and Research, Pune (Collaboration)
- University of St Andrews (Collaboration)
- Tata Institute of Fundamental Research (Collaboration)
- University of Laval (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- QUEEN MARY UNIVERSITY OF LONDON (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- Indian Institute of Technology Bombay (Collaboration)
- Indian Institute of Technology Kanpur (Collaboration)
Publications
Leech MC
(2021)
Anodic Oxidation of Aminotetrazoles: A Mild and Safe Route to Isocyanides.
in Organic letters
Leech M
(2020)
Electrosynthesis Using Carboxylic Acid Derivatives: New Tricks for Old Reactions
in Accounts of Chemical Research
Leech M
(2020)
Organic electrosynthesis: from academia to industry
in Reaction Chemistry & Engineering
Lam K
(2022)
Electrosynthesis: A Practical Way to Access Highly Reactive Intermediates
in Synlett
Garcia A
(2020)
Anodic Oxidation of Dithiane Carboxylic Acids: A Rapid and Mild Way to Access Functionalized Orthoesters
in Organic Letters
Description | We have recently discovered a method to generate O and N centred radicals without the need to use any catalyst of toxic reagent during the electrolysis by using fluorinated solvents. First results have shown that we can form O heterocycles easily from simple aromatic acids. This has already led to several publications where we demonstrated that our radicals (O centred, oxycarbonyls, etc.) could be used for the preparation of pharmaceutically relevant fragments. We have also explored the use of manganese salt as electrochemical redox mediators. We have successfully used them for the generation of O-centred radicals from simple cyclobutanols. Finally, recently, we successfully generated nitrogen centred radicals, and we are currently working on the optimisation of the process to prepare bioactive nitrogen heterocycles. |
Exploitation Route | We have published our new methodologies in several articles and on social networks (Twitter, Facebook and Linkedin). As a result, several universities and industries have invited us to give talks due to their interest in these new electrochemical methodologies. These companies (pharmaceutical and agrochemical) have shown a vivid interest in adding electrochemical methods into their portfolio of synthetic techniques since it is not only a green and economically-relevant method to activate small molecules. |
Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |
Description | The findings in our research has been used by industrial partners for their processes. Unfortunately more information cannot be disclosed at the moment due to IP. |
First Year Of Impact | 2022 |
Sector | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Impact Types | Societal,Economic |
Description | GSK PhD Case proposal |
Amount | £32,000 (GBP) |
Organisation | GlaxoSmithKline (GSK) |
Sector | Private |
Country | Global |
Start | 10/2021 |
End | 10/2024 |
Description | 3D printing for electrochemistry |
Organisation | University College London |
Department | School of Pharmacy |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We got in touch with Dr Stephen Hilton at UCL, who is an expert in 3D printing, and developed a cheap and very versatile flow cell to be used on the Electrasyn equipment. Our team helped with the design, tested it and developed a new flow methodology to make MOM-ethers. |
Collaborator Contribution | Dr Hilton helped with the design of the cell and 3D printed the system. |
Impact | Publication: https://onlinelibrary.wiley.com/doi/full/10.1002/celc.201900815 3D printing, organic synthesis and electrochemistry |
Start Year | 2019 |
Description | Anodic generation of diazo compounds |
Organisation | University of Laval |
Country | Canada |
Sector | Academic/University |
PI Contribution | Prof Thierry Ollevier has noticed our recent outputs in the field of organic electrochemistry. After discussing with him we have decided to embark on a new project where we will develop a safe and easy electrochemical method for the generation of diazo compounds using electrosynthesis using our results on the anodic generation of N-centred radicals. |
Collaborator Contribution | Professor Ollevier is an expert in diazo chemistry and is guiding the project when it comes to the reactivity of these compounds. Nour Tanbouza, one of his students, is performing an internship with us too. |
Impact | None yet. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | Indian Institute Of Science Education & Research |
Country | India |
Sector | Academic/University |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | Indian Institute of Science Education and Research, Pune |
Country | India |
Sector | Charity/Non Profit |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | Indian Institute of Technology Bombay |
Country | India |
Sector | Academic/University |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | Indian Institute of Technology Kanpur |
Country | India |
Sector | Academic/University |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | Institute of Chemical Technology (ICT) |
Country | India |
Sector | Academic/University |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | Queen Mary University of London |
Department | Queen Mary Innovation |
Country | United Kingdom |
Sector | Private |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | Tata Institute of Fundamental Research |
Country | India |
Sector | Public |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Creation of the India-UK Innovation & Sustainability Chemistry Consortium |
Organisation | University of St Andrews |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Our research was noticed by Indian and UK colleagues, and we were invited to be part of the founding members of the India-UK ISCC. ISCC is an international multidisciplinary chemistry network providing a training and research environment for future international chemistry leaders in India and the United Kingdom. At the moment, the initiative has been funded and supported by both the UK government and the RSC. |
Collaborator Contribution | In 2021, we will start collaborating on the electrogeneration of O and N centred radicals with other partners of the consortium. |
Impact | No output per se yet, but we have established the consortium and had an official launch in the RSC president and UK government officials' presence. |
Start Year | 2020 |
Description | Cyclobutanol radicals |
Organisation | Imperial College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Looking for new methods to make O centred radical, we have developed an elegant new methodology, using Mn(II)/Mn(III) to generate O centred radicals from cyclobutanols. |
Collaborator Contribution | Our colleague, Phil Parsons had initially developed a method using to generate cyclobutanol O radicals using NBS and other oxidants. We transposed his methodology to electrochemistry. |
Impact | Regioselective Electrochemical Cyclobutanol Ring Expansion to 1-Tetralones - A. Petti, P. Natho, K. Lam, P. J. Parsons, Eur. J. Org. Chem. 2021, 2021, 854. |
Start Year | 2020 |
Description | Pride in STEM |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Matthew Leech is presenting his work funded by EPSRC during a Pride in STEM event hosted by the Royal Society in Chemistry. Pride in STEM is a charitable trust run by an independent group of LGBT+ scientists & engineers from around the world. They aim to showcase and support all LGBT+ people in STEM fields. |
Year(s) Of Engagement Activity | 2020 |
URL | https://prideinstem.org/ |