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In Drug Creation, Less Precious, More Green

 

Some of the most rare and expensive metals in the world — palladium, platinum, iridium, and even gold — have long been used to create drugs. But now scientists are finding cheaper, greener alternatives.

Building a drug is like constructing a house from small molecules. In this process, precious metals are an essential tool to facilitate, or catalyze, the formation of chemical bonds. Palladium, for example, a rare, silvery-white metal used in many well-known drugs, helps the carbon atoms of two different materials form bonds. Many of today’s drugs, from cancer medications to rheumatoid arthritis treatments, could not be made without the help of these catalysts.

The “Magic Dust” Of Drug Development

While precious metals are the “magic dust to help build drugs,” according to Pfizer chemist Sebastien Monfette, they’re not very sustainable. Miners have to excavate a large amount of land to extract these metals, compared to more abundant materials such as iron or nickel. “We need large quantities of these metals, but they’re not very common in the earth’s crust. It creates a huge amount of pollution to harvest these metals,” said Monfette, who's based at Pfizer’s Groton, Connecticut site. These precious metals are also very expensive.  

Walk into a research lab, and don’t expect to be wowed by gleaming gold bars and shiny rocks. Metal catalysts are used in powder form, by the milligram. Clockwise from top left: Iron, Cobalt, Nickel, Gold, Palladium, Iridium, Rhodium, and Ruthenium. (Courtesy of Sebastien Monfette)

Leaner, Greener Chemistry

In search of those alternate supplies, Monfette and his colleagues set out to find a replacement for palladium, which costs up to 3,000 times more than cheaper metals. They chose the non-precious metal nickel, which is much more abundant in the earth, and thus produces less carbon waste in harvesting it, and is less toxic than palladium and therefore generates less waste in the drug purification process. 

But the challenge with using nickel as a catalyst is that it quickly decomposes when exposed to air. “It’s harder to tame and has uncontrollable reactivity,” said Monfette. “Think of the Statue of Liberty (made of copper) or silverware, these metals turn green and brown when exposed to the air because they’re so reactive.”

After a year of testing, in 2015 Monfette and his team published their findings in the journal ACS Catalysis: they created a stable form of nickel, which could prove to be a cheaper, greener catalyst than palladium.  While it’s still being tested for future use, Monfette hopes it helps more of the industry recognize that precious metals can be swapped out for other materials. “With drug discovery, it’s like you’re building a house very quickly,” he said. “And we’re coming up with new, cheaper, more sustainable tools to help do it.”