In her winning essay in SCI Scotland’s Postgraduate Researcher competition, Marina Economidou, first year PhD Student at GSK/The University of Strathclyde, talks about palladium recovery.

Each year, SCI’s Scotland Regional Group runs the Scotland Postgraduate Researcher Competition to celebrate the work of research students working in scientific research in Scottish universities.

This year, four students produced outstanding essays in which they describe their research projects and the need for them. In the second of this year’s winning essays, Marina Economidou explains the need for palladium recovery and making it more efficient.

Pictured above: Marina Economidou

U-Pd-ating the workflows for metal removal in industrial processes

Palladium-catalysed reactions have great utility in the pharmaceutical industry as they offer an easy way to access important functional motifs in molecules through the formation of carbon-carbon or carbon-hetero-atom bonds.

The superior performance of such reactions over classical methodologies is evident in modern drug syntheses, where Buchwald-Hartwig, Negishi or Suzuki cross-coupling reactions are frequently employed.

However, the demand for efficient methods of palladium recovery runs parallel to the increased use of catalysts in synthesis. The interest in metal extraction can be attributed to several reasons.

Cross-coupling steps are usually situated late in the synthetic route, resulting in metal residues in the final product. In addition to possessing intrinsic toxicity, elemental impurities can have an unfavourable impact on downstream chemistry.

Hence, their limit must be below the threshold set by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).

The need for palladium recovery

However, the importance of palladium recovery does not only arise from the need to meet regulatory criteria. The volatility of palladium supply as a result of geopolitical instabilities has been a focus of attention this year, with Russia producing up to 30% of the global supply and prices reaching an all-time high of £81,179 per kilogramme.

Therefore, aside from the need to remove metals from the product for regulatory reasons, there is a desire to recover metals from waste streams as effectively as possible due to their finite nature and high costs.

The sustainability benefits of recovery for circular use are an additional incentive for an efficient extraction process, as catalysts can be regenerated when metal is returned to suppliers.

The increasing pressure for greener processes and more ambitious sustainability goals – such as GlaxoSmithKline’s environmental sustainability target of net zero impact on climate by 2030 – also contribute to the need for further refinement of working practices.

>> SCI's Scotland Group connects scientists working in industry and academia throughout Scotland.

Palladium has many uses including in catalytic converters, surgical instruments, and dental fillings.

Improving extraction processes

It is essential to have well-controlled and reproducible processes for pharmaceutical production, as redevelopment requires further laboratory work and additional time and resources.

With several industry reports on the inconsistent removal of palladium following catalytic synthetic steps, there seems to be a knowledge gap as to which factors affect the efficiency of extraction and why there can be significant differences between laboratory and plant conditions.

The focus of my PhD is investigating the speciation of palladium in solution in the presence of pharmaceutically relevant molecules, to offer an insight into the efficiency of metal extraction at the end of processes.

By understanding the oxidation state and coordinative saturation of the palladium species formed in the presence of different ligands, a better relationship could be established between the observed performance of metal extraction processes under inert and non-inert conditions.

With the wide breadth of ligands and extractants that are now commercially available for cross-coupling reactions, my ambition is to generate a workflow for smart condition selection that not only achieves selective metal recovery, but is scalable and can be transferred to plant with consistent performance.

The cost and preciousness of metal catalysts are both factors that prohibit their one-time use in processes. Understanding how palladium can be extracted and recovered in an efficient manner will not only deliver reliable processes that meet the demands of the market in the production of goods, it will also lead to economic and environmental benefits.

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>> Read Angus McLuskie’s winning essay on replacing toxic feedstocks.

>> Our Careers for Chemistry Postdocs series explores the different career paths taken by chemistry graduates.