Electrochemical generation of oxygen and nitrogen centred radicals

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.

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.