It’s hard to find a place on Earth untouched by palladium. The silvery-white metal is a key part of catalytic converters in the world’s 1.4 billion cars, which spew specks of palladium into the atmosphere. Mining and other sources add to this pollution. As a result, traces of palladium show up in some of the most remote spots on Earth, from Antarctica to the top of the Greenland ice sheet.
Palladium is also practically indispensable for making drugs. That’s because catalysts with palladium atoms at their core have an unmatched ability to help stitch together carbon–carbon bonds. This kind of chemical reaction is key to building organic molecules, especially those used in medications. “Every pharmaceutical we produce at some point or another has a palladium-catalysed step in it,” says Per-Ola Norrby, a pharmaceutical researcher at drug giant AstraZeneca in Gothenburg, Sweden. Palladium-catalysed reactions are so valuable that, in 2010, their discoverers shared a Nobel prize.
But despite its versatility, chemists are trying to move away from palladium. The metal is more expensive than gold, and molecules that contain palladium can also be extremely toxic to humans and wildlife. Chemical manufacturers have to separate out all traces of palladium from their products and carefully dispose of the hazardous waste, which adds extra expense.
Thomas Fuchß, a medicinal chemist at the life-sciences company Merck in Darmstadt, Germany, gives the example of a reaction to make 3 kilograms of a drug molecule for which the ingredients cost US$250,000. The palladium catalyst alone adds $100,000; purifying it out of the product another $30,000.
Finding less-toxic alternatives to the metal could help to reduce environmental harm from palladium waste and move the chemicals industry towards ‘greener’ reactions, says Tianning Diao, an organometallic chemist at New York University. Researchers hope to swap palladium for more common metals, such as iron and nickel, or invent metal-free catalysts that sidestep the issue altogether.
Several times in the past two decades, researchers have reported finding palladium-free catalysts. But in what has become a recurring pattern for the field, each heralded discovery turned out to be a mistake.
Then, last year, came an exciting result. A stunning report in January 2021 seemed to put the palladium-free dream within reach1. Researchers in China reported that a ‘carbon coupling’ reaction, one of the most common carbon-bond-forming reactions in the drug industry, could be catalysed without palladium or any other metal. If the findings were confirmed, the reaction would change everything we know about how carbon bonds are formed, says Norrby.
Chemists were instantly excited — and sceptical. Researchers around the world attempted to verify the extraordinary claims in their own laboratories. Within two months, three teams published preprints (working papers prior to peer review) arguing that palladium contamination was catalysing the coupling reaction.
Those critics would turn out to be right (see ‘Carbon coupling’). The discovery-that-wasn’t, and questions about how the mistake was made, has dominated discussion in some analytical and pharmaceutical chemistry circles. The saga serves as a cautionary tale about how incredibly difficult it is for chemists to keep their reactions and laboratories free from palladium contamination.
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