Chemical tool created to simplify carbon-nitrogen bonds and reduce the cost of medicines

In many prescriptions, a strong connection between carbon and nitrogen is crucial. Nearly two-thirds of current drugs depend on these bonds for their core structure, according to one analysis.

Researchers have now revealed a tool that helps form these bonds in a simpler way. AshPhos, the new molecule in question, is designed to cut down on production expenses for treatments.

Dr. Sachin Handa from the University of Missouri and his team, in collaboration with Biohaven Pharmaceuticals, oversaw this work.

Their goal was to make the process cleaner and less expensive by taking advantage of inexpensive materials that stay active throughout important reactions.

Ashphos explained

AshPhos is a ligand, which is a molecule that joins with a metal to run a chemical reaction. This type of reaction can join carbon and nitrogen in ways that many medicines depend on.

“What makes AshPhos special from other existing ligands is that it’s made from inexpensive and easy-to-find materials, and it is far better in terms of activity and efficiency,” said Handa.

Cheaper medicine production

Some researchers note that manufacturing is a big slice of a drug’s price. A streamlined method for forming carbon-nitrogen connections can reduce costly steps, which often drive final expenses up for patients.

“It’s eco-friendly because it’s made with less waste and uses materials from renewable sources,” said Handa.

Science behind Ashphos

AshPhos latches onto a palladium metal atom. It maintains the metal’s strength under harsh conditions and keeps it from dropping out of the reaction.

“This is important for highly challenging bulky molecules that otherwise deactivate the catalyst in the absence of AshPhos,” said Handa.

Most ligands lose grip once the heat goes up and conditions change. This new molecule has a way to reconnect if it detaches, which allows the reaction to proceed efficiently.

“It acts as a ‘boss’ by directing the metal what to do, ensuring the metal stays active and selective during the process,” said Handa.

Broader energy uses

Besides pharmaceuticals, AshPhos could help develop nanomaterials that assist in hydrogen production. Some see hydrogen as a clean fuel, so better methods for its generation may attract interest.

Researchers also want to check whether AshPhos can interact with certain metals to tackle “forever chemicals,” known as PFAS, because these pollutants often resist normal breakdown pathways.

Real-world testing and results

To test how well AshPhos performs, the team tried it on several difficult chemical reactions using heteroaryl halides and bulky amines. These are often problematic because the molecules interfere with each other and make the metal catalyst stop working.

Even under tough conditions, AshPhos held up. It delivered strong results with dozens of combinations, including some that didn’t work with previous ligands.

In one test, it produced a 90% yield in just 2 hours—a sign that this method could shorten production time and reduce costs.

Comparison with existing tools

The researchers compared AshPhos with GPhos, a well-known ligand in this type of reaction. In side-by-side trials, AshPhos consistently delivered higher yields and required milder conditions and cheaper materials to work.

For example, when coupling a tough heteroaryl bromide with a hindered amine, GPhos gave only a 45% yield.

Under the same conditions, AshPhos reached 60%. In another case, AshPhos delivered a 90% yield where GPhos stalled at 65%.

Scaling up for industry

The team didn’t stop at lab-scale success. They pushed AshPhos into a larger reaction setup, running it at ten times the normal size to see how it would perform with lower amounts of catalyst.

It worked just as well. Even with a 90% drop in catalyst use, the reaction still gave an 81% yield—almost the same as the smaller trial.

This result hints that AshPhos could be ready for industrial-scale drug production without needing major changes.

Why AshPhos matters

Handa’s personal experiences showed him that affordable treatment is an urgent need. He hopes that if production steps become less complicated, more people can have access to essential medicines.

“Our ligand is very strong – it’s like locking a door with a key, ensuring it stays securely closed and won’t open,” said Handa.

The team is exploring ways to use this method for newer treatments. They see potential for simpler manufacturing steps, fewer waste products, and reduced reliance on pricey reagents.

“It will also make medicine production cheaper, helping more people afford the medications they need,” said Handa.

The study is published in JACS Au.

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