Precious Metal Catalysts: The Scavengers’ Guide

There’s no doubt that catalysis has played a significant role in the global chemical industry over the past few decades – recognized by numerous recent Nobel Prizes in Chemistry: Knowles, Noyori, and Sharpless’ work for asymmetric catalysis (2001), Schrock, Grubbs, and Chauvin’s work on alkene metathesis (2005), and Suzuki, Heck, and Negishi’s work on the development of cross-coupling chemistry (2010).

In pharma, under constant pressure to reduce time to market for successful drugs, process chemistry teams must find the most cost-effective and scalable synthetic route as quickly as possible. At the same time, driven by the pursuit of increasingly difficult therapeutic targets, discovery teams are probing molecules that contain synthetically challenging motifs, such as macrocycles, spirocycles, and multiple stereocenters. To address the challenges presented by more complex structures, process development chemists have embraced new methodologies, many of which involve precious metal catalysis. For example, the development of macrocyclic protease inhibitors to treat hepatitis C infections led to the refinement and adoption of ruthenium-catalyzed ring-closing metathesis macrocyclization at the industrial scale (1).

Pharmaceutical manufacturers employ a variety of platinum group metal (PGM) catalysts to facilitate the production of APIs and regulatory starting materials. But doing so presents challenges, such as rising metal costs and the need to remove metal impurities. This latter challenge can be addressed by selecting the most efficient catalyst and limiting catalyst loading as much as possible. After loading has been optimized, attention turns to the removal of elemental impurities through various purification steps.

PGM catalysts are expensive – as you’d expect with precious metals – and subject to price fluctuations (PGMs are traded on the public market). And so, we believe it makes sense to consider a closed-loop approach to the catalyst lifecycle that makes the most of scavenging. The possibilities for scavenging are diverse – from simple charcoal slurry and filtration to more complex solutions, such as functionalized resins and silicas. The key is efficiency. Once a closed loop is implemented, the majority of the metal price is paid only once; recovered metal can be applied as credit toward future purchases of the finished catalyst. Moreover, as the recovered metal will be stored in metal weight rather than currency, it will be insulated from market fluctuations.

Implementing a recycling approach requires chemists to work closely with engineers, smelters, and supply chain experts to appropriately plan, design and implement the recovery solution. Collaboration and transparency between a refiner and manufacturer are vital to ensure the recycling plan is practical and effective. When choosing the right refining partner for a process, you should, of course, consider maximum recovery and fast processing turnarounds, but you should also think about transparency, communication, and overall support – just as you would with any outsourcing partner.

The refiner will need to obtain a representative sample of the overall spent catalyst and to understand how much of the PGM content in the catalyst is recoverable. Here, direct sampling techniques (without incineration) usually provide more accurate insights into a broad range of solid and liquid spent industrial catalysts. When sampling is completed, refiners must accurately and reliably measure the precious metal content of the materials being reclaimed, using a wide variety of sensitive analytical instruments and techniques.

Pharmaceutical companies are typically not able to sample and assay in-house, so you will be reliant on your refining partner. And that’s why transparency – and trust – are so important.

The application of catalysis within the pharmaceutical industry is rapidly evolving. With the availability of novel laboratory tools for characterization, new approaches to synthesis and advanced computational capabilities, we have unparalleled potential for making significant advances in modern development. But as the industry continues to design innovative processes, let’s not overlook the opportunities for precious metal recovery.