Earth-Abundant Metal Catalysis in the Production of Pharmaceutical Drugs
Lead Research Organisation:
University of Bristol
Abstract
There is a pressing need to accelerate research and development within the life science industry, decreasing the time taken to bring new medicines to patients, while reducing the environmental impact of pharmaceutical production. This must be achieved within the wider societal drive towards Net Zero.
There are three classes or ‘scopes’ of CO2 emission that manufacturers need to take into account on the path to Net Zero: Scope 1, direct emissions; Scope 2, indirect emissions from purchased energy and Scope 3, indirect emissions that occur in the upstream and downstream activities of an organisation. As part of their ‘Ambition Net Zero’, pharmaceutical company AstraZeneca (AZ) have reduced Scope 1&2 emissions by 68% since 2015, however, the more challenging Scope 3 emissions account for >95% and they are committed to reducing these by 90% by 2045. New, more sustainable approaches to the production of Active Pharmaceutical Ingredients (APIs) – the active components in medicines – has been identified as the key area for reductions in emissions.
‘Catalysis’ is one of the 12 ‘principles of green chemistry’ due to the reduced environmental impact it bestows compared with non-catalysed transformations and palladium catalysed transformation are widely exploited in the production of APIs. Unfortunately, palladium is not only expensive (currently £24,000/kg), but has an exceptionally high carbon footprint. The extraction of 1kg of palladium produces nearly 4 tonnes of CO2 and requires ~200,000L of water. In the proposed drEAMcat Prosperity Partnership we will target its replacement with far more sustainable ‘Earth abundant metals’ (EAMs). EAMs such as copper, cobalt, nickel and iron are overwhelmingly cheaper and less environmentally damaging than palladium. For instance, iron ore costs around 8p/kg and its extraction liberates only 1.5 kg CO2 per kg.
While this is easy to say, in practice it is very challenging to achieve. EAMs behave very differently to palladium. Coercing them into acting in a similar manner requires the development of a deep understanding of the ‘mechanisms’ of reaction: the way in which the fundamental chemical transformations occur. Mechanistic investigations can be laboriously slow, often taking many years to complete.
To achieve the goal of replacing palladium with EAMs, drEAMcat will unite leading experts at AZ, the University of Bristol and Labman, a leading developer of automated laboratory tools. Using a combined approach of high-throughput experimentation and digital chemistry we aim to reduce the timescale of the mechanistic studies from years to weeks or days, allowing rapid implementation of EAM-catalysed processes.
Reduced emissions is not the only benefit with EAM catalysis. The very fact that EAMs behave differently to palladium allows the development of new catalytic transformations that simply aren’t accessible with this metal. This will lead to further significant impacts. Firstly, it will enable alternative routes to API’s, shortening development and production times, leading to extensive cost savings and reduced waste. Secondly, it will open-up new realms of ‘chemical space’, facilitating the discovery and launch of new medicines in a faster and more efficient manner.
The reduction in environmental harm, combined with shortening the time between drug discovery and transformative patient outcomes, will not only impact directly on AZ’s business, but on the wider life science sector, society and the economy in the UK and beyond.
There are three classes or ‘scopes’ of CO2 emission that manufacturers need to take into account on the path to Net Zero: Scope 1, direct emissions; Scope 2, indirect emissions from purchased energy and Scope 3, indirect emissions that occur in the upstream and downstream activities of an organisation. As part of their ‘Ambition Net Zero’, pharmaceutical company AstraZeneca (AZ) have reduced Scope 1&2 emissions by 68% since 2015, however, the more challenging Scope 3 emissions account for >95% and they are committed to reducing these by 90% by 2045. New, more sustainable approaches to the production of Active Pharmaceutical Ingredients (APIs) – the active components in medicines – has been identified as the key area for reductions in emissions.
‘Catalysis’ is one of the 12 ‘principles of green chemistry’ due to the reduced environmental impact it bestows compared with non-catalysed transformations and palladium catalysed transformation are widely exploited in the production of APIs. Unfortunately, palladium is not only expensive (currently £24,000/kg), but has an exceptionally high carbon footprint. The extraction of 1kg of palladium produces nearly 4 tonnes of CO2 and requires ~200,000L of water. In the proposed drEAMcat Prosperity Partnership we will target its replacement with far more sustainable ‘Earth abundant metals’ (EAMs). EAMs such as copper, cobalt, nickel and iron are overwhelmingly cheaper and less environmentally damaging than palladium. For instance, iron ore costs around 8p/kg and its extraction liberates only 1.5 kg CO2 per kg.
While this is easy to say, in practice it is very challenging to achieve. EAMs behave very differently to palladium. Coercing them into acting in a similar manner requires the development of a deep understanding of the ‘mechanisms’ of reaction: the way in which the fundamental chemical transformations occur. Mechanistic investigations can be laboriously slow, often taking many years to complete.
To achieve the goal of replacing palladium with EAMs, drEAMcat will unite leading experts at AZ, the University of Bristol and Labman, a leading developer of automated laboratory tools. Using a combined approach of high-throughput experimentation and digital chemistry we aim to reduce the timescale of the mechanistic studies from years to weeks or days, allowing rapid implementation of EAM-catalysed processes.
Reduced emissions is not the only benefit with EAM catalysis. The very fact that EAMs behave differently to palladium allows the development of new catalytic transformations that simply aren’t accessible with this metal. This will lead to further significant impacts. Firstly, it will enable alternative routes to API’s, shortening development and production times, leading to extensive cost savings and reduced waste. Secondly, it will open-up new realms of ‘chemical space’, facilitating the discovery and launch of new medicines in a faster and more efficient manner.
The reduction in environmental harm, combined with shortening the time between drug discovery and transformative patient outcomes, will not only impact directly on AZ’s business, but on the wider life science sector, society and the economy in the UK and beyond.