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Chemists discover simple way to build bigger molecules, one carbon at a time

A team of chemists at the University of Cambridge has developed a powerful new method for adding single carbon atoms to molecules more easily, offering a simple one-step approach that could accelerate drug discovery and the design of complex chemical products.

The research, recently in the journal Nature under the title "One-carbon homologation of alkenes," unveils a breakthrough method for extending molecular chains—one carbon atom at a time. This technique targets alkenes, a common class of molecules characterized by a double bond between two carbon atoms. Alkenes are found in a wide range of everyday products, from anti-malarial medicines like quinine to agrochemicals and fragrances.

Led by Dr. Marcus Grocott and Professor Matthew Gaunt from the Yusuf Hamied Department of Chemistry at the University of Cambridge, the work replaces traditional multi-step procedures with a single-pot reaction that is compatible with a wide range of molecules.

Dr. Grocott explains, "Alkenes are common and incredibly useful structures in chemistry, but until now, there hasn't been a straightforward way to selectively add just one carbon atom to them."

The key to this new method is a cleverly engineered component—an ingenious chemical tool based on an allyl sulfone "1-carbon transfer reagent," designed to add a single carbon atom at a time. First, the specially designed molecule attaches to the target compound and starts a reaction that bonds them together. Then, it quickly reshapes itself, ending with one extra carbon in place—like snapping a new Lego piece onto a growing chain.

"It's a smart and simple design," says Gaunt. "Each part of the molecule has a specific role. One part helps trigger the final step, another controls the timing, and another helps it stick to the target at the beginning."

To show how well their new method works, the scientists tested it on a medicine called cyclosporine A. This medicine helps stop the immune system from overreacting by sticking to a special protein in the body. The Cambridge scientists made new versions of the medicine by adding one or two carbon atoms. These new versions still stuck to the protein and some of them still slowed down the immune system, while others didn't. That means it might be possible to change what the medicine does without turning off the immune system completely.

"This is about more than extending molecules," said Professor Gaunt. "It's about giving chemists a new way to explore chemical space and unlock previously inaccessible drug variants."

The ability to fine-tune molecules with such precision could be transformative for medicinal chemistry, where even small changes in structure can have a big impact on how a drug works in the body. The approach also allows for the introduction of functional groups, offering further versatility in molecule design.

Beyond the pharmaceutical industry, this method could find applications in areas such as crop protection and advanced materials—anywhere that subtle changes to carbon chains affect performance and function.

"This new chemistry gives us control over molecular structure in a way that's both simple and broadly useful," added Dr. Grocott. "It opens the door to designing smarter, better-targeted compounds across a range of industries."

In the past, adding carbon atoms to molecules like this was slow and took many complicated steps. But the Cambridge team discovered a groundbreaking new way to do it—faster, easier and all in one go. This big step forward could help scientists design new medicines much more quickly and easily than before.