Chemists at University of Chicago have developed a new chemical technique that could make it much easier and faster to create future medicines.
The breakthrough allows scientists to quickly modify molecules by replacing certain carbon-oxygen structures with nitrogen atoms.
According to the researchers, this process could dramatically speed up drug discovery by reducing complicated chemical procedures from as many as 10 steps down to just one or two.
The study was published in Science.
Many medicines people take today belong to a category called small-molecule drugs.
These include common painkillers like ibuprofen as well as drugs used to treat cancer, eczema, infections, and many other diseases.
Before a new drug can be tested, however, scientists first need to build the molecule itself in the laboratory.
This can be extremely difficult because molecules are made of atoms connected in very specific arrangements. Even changing the position of a single atom can completely alter how a drug behaves inside the body.
For example, moving one nitrogen atom might determine whether a medicine successfully attaches to its target in the body or fails entirely.
Because of this, chemists often spend huge amounts of time creating slightly different versions of the same molecule to test which design works best.
The UChicago team wanted to find a much simpler way to introduce nitrogen atoms into molecules.
According to Guangbin Dong, the senior author of the study, the goal was to make it easier to create many different molecular variations quickly.
The researchers focused on structures called carbonyl groups, which are made of carbon and oxygen atoms bonded together. Carbonyl groups are extremely common in small-molecule drugs.
Previously, the team had already discovered ways to move carbonyl groups around inside molecules more easily. But this time, they wanted to replace those groups with nitrogen atoms instead.
Nitrogen is especially important in medicines because it often plays a key role in interacting with proteins and biological targets inside the body.
The scientists discovered a new method using a chemical ingredient called NAHA. This compound grabs onto the carbonyl group and breaks its bond. Then, through a carefully controlled sequence of reactions, a nitrogen atom moves into the empty position.
The researchers described the process as similar to dancers switching partners during a choreographed routine.
One major advantage of the method is its flexibility. The reaction works with many different molecular attachments, including ones that are normally difficult to handle in chemical synthesis.
Graduate student Zining Zhang, the paper’s first author, said the reaction felt almost like a “dream reaction” because it worked so smoothly and efficiently.
The researchers hope the technique will give scientists a powerful new tool for designing and testing potential medicines more rapidly.
In the future, the team plans to continue developing methods that allow chemists to swap carbonyl groups for other useful atoms as well, opening even more possibilities for creating new drugs and chemical materials.
