Bespoke Bimetallics for Chemical Cooperativity

The importance of the UK's chemical and pharmaceutical sector can be seen in the statistic that it supplies £60M of added value each working day (that equates to £15bn a year) to our Gross Domestic Product (the total value of goods and services provided by a country in one year).

Cutting edge research, innovation and sustainability lie at the heart of this project. The research is in organometallic chemistry, a core area of chemistry that is utilised in a myriad of real world applications, spanning chemistry and other disciplines such as biochemistry and material science. Organometallic compounds, comprising an organic moiety and a metal moiety are essential tools for constructing molecules big and small. A large proportion of known chemical processes depend on the metal moiety of organometallic compounds being a precious transition metal (commonly palladium, platinum, rhodium, iridium, ruthenium, and osmium), which are essential for the manufacture of numerous specialty chemicals from agrochemicals through to pharmaceuticals (especially anticancer drugs).

Base (non-precious) metals are generally much cheaper (due to their higher natural abundance) and reflecting this high abundance in the earth's crust they have less toxicity concerns than their precious metal counterparts. The problem is their chemistry (their ability to carry out useful reactions efficiently) is rather limited by comparison so more often than not they are inefficient in many chemical processes. If base metal chemistry could be developed to the status of precious transition metal chemistry or better still to go beyond this status, then sustainability would be significantly improved and reliance on less environmentally benign precious transition metals would be reduced.

Recent advances by the research team have demonstrated that base chemistry can be made orders of magnitude more efficient by preparing organometallic compounds that contain two base metal elements instead of one. The metal common to all of these metal pairs is an alkali metal (lithium, sodium or potassium), while the second metal is magnesium, zinc, aluminium or the earth-abundant transition metals iron and manganese. By forming mixed-metal bimetallic structures impossible in single-metal systems, cooperative effects are induced which transform the reactivity of the base metals opening up a vast number of novel reactions that are currently inaccessible to base metals on their own. Cooperativity will be especially important in our targeted C-C bond formations and C-F bond activations through alkali metal -Fe or -Mn partnerships as currently these reactions are generally the domain of precious transition metal catalysis.

Realising this escalation of sustainable base metal chemistry will be a major breakthrough in itself but this project will take on an additional ambitious challenge. Alkali metal organometallic chemistry invariably needs to be performed under anaerobic conditions as the compounds involved rapidly decompose with even traces of air or moisture. However, the team recently made the extraordinary finding that certain organoalkali metal reactions could be run under aerobic conditions by using Deep Eutectic Solvents (DES) as opposed to industry standard classical organic solvents. DES are more cost-effective, greener and biorenewable than organic solvents and switching to them would also do away with the need for costly inert atmosphere protocols. The proof of concept results with DES have been with single base metals, so the challenge is to develop this new bimetallic chemistry in DES. Success will impact the practice of organometallic chemistry worldwide.

There is huge potential scope for widespread impact of cooperative bimetallic chemistry in manufacturing underpinning technological developments over several sectors and thus contributing to a more productive UK economy.

Advancing the bimetallic chemistry of earth-abundant elements will ensure sustainability of numerous ongoing and yet to be discovered chemical processes to mitigate overexploitation and environmental concerns of precious transition metals. The cooperativities induced by bimetallic pairings promise not just emulation of precious transition metal chemistry that exceeds the limits of single-metallic systems; but also new chemistry unknown even with precious transition metals.

Developing innovative atom-economical, greener solvent, mild temperature earth abundant mixed-metal synthetic methodologies for functionalising organic molecules with "incompatible" groups will have economic benefits in the scale up of industrial processes. The impact of new technologies, based mainly on environmentally-friendly solvents such as DESs, would be of substantial long term benefit to large multinational industries (e.g. pharmaceutical, agrochemical, organic materials, and cosmetic). Many advantages would be realised including greater sustainability, safer working practices, and large cost savings as well as minimising use or generation of toxic chemicals. Every UK household could potentially benefit as numerous commodity chemicals (pharmaceuticals, cosmetics, dyes, polymers, etc.) need polar organometallic methodologies in their preparation. Accessing pharmaceuticals at lower prices is a priority public policy issue. Continued pharmaceutical innovation is also essential for increases in longevity, a better health, higher productivity and economic growth. Note that one common salt used for synthesising DESs is choline chloride, which is produced on a scale of million metric tons per year (ca. 2 £/Kg) and it is not only cheap and extractable from biomass but also non-toxic and biodegradable. Collectively, fundamental understanding and bimetallic technologies generated during this project will allow for rapid exploitation and commercialisation of mixed-metal reagents. The impact of this work will be felt in various areas, most directly those dealing with fine chemicals manufacturing, minimising its environmental impact.

As processes using cooperative bimetallics and DES are implemented by industry, fine chemical and pharmaceutical manufacturing will change, incorporating these more economical and sustainable methodologies, that will have a positive impact on wealth and environment. Our industrial partner Janssen has immediately seen the potential benefits of this work. Janssen will provide industry pull advice and assistance to this project. To ensure this research is widely disseminated a twitter account highlighting our own and competitor developments in bimetallic chemistry and DES applications in polar organometallic chemistry will be created. A 'Power Symposium" is also planned in year 2 on the applications of cooperative bimetallics, highlighting challenges within the development of transition-metal free bond forming protocols and the use of novel solvent systems, connecting with both industrial stakeholders and expert researchers in organometallic chemistry.

This project will also provide training/networking opportunities for both PDRAs, enabling them to launch their careers in this exciting, rapidly growing field. Their development will be broadened by interactions with the European academics and industrialists involved in the project, with the latter giving them valuable insight into the industrial context of their research. The UK will therefore benefit from trained researchers and potentially licensable new technologies using cooperative bimetallics and DES. A variety of public engagement activities and media coverage will be pursued to ensure the wider public recognizes the implications of this project.