Boron compounds offer new method for improving existing drugs

Researchers at the University of Gothenburg are simplifying drug development by creating a new class of stable boron-fluorine compounds. The research could allow scientists to improve the effectiveness of medicines or reduce their side effects without having to break the drug down and rebuild it from scratch. 

Boron-based chemical compounds are already used throughout modern chemistry. They are widely used in the development of pharmaceuticals, advanced materials and molecules for medical diagnostics. However, some boron compounds are still difficult to manufacture, particularly when a boron atom must be positioned with extreme precision inside a complex molecule. This challenge has limited the ability of researchers to further refine existing drugs and other biologically active substances.

No time-consuming purification

In the new study, the Gothenburg team developed a group of compounds known as BF₂-boracycles. According to the researchers, these compounds are both stable and easy to use.

“In our study, we have developed a new class of stable and easy-to-use boron compounds, known as BF₂-boracycles. These can be produced in a simple, metal-free and scalable way without time-consuming purification steps. The compounds are also unusually stable but at the same time highly reactive when used in chemical reactions,” says Henrik Sundén, Professor of Organic Chemistry at the University of Gothenburg.

A key advantage of BF₂-boracycles is their ability to modify complex molecules at a late stage of development. This means researchers can take an existing drug and add new chemical functions in a controlled way, potentially improving its therapeutic effect or reducing unwanted side effects.

Compared with current approaches, the method requires fewer steps during drug design, generates less waste and uses resources more efficiently. These benefits also make the process more environmentally friendly. The work was carried out in collaboration with the University of Caen in France and the University of Ljubljana in Slovenia.

Replacing a hydrogen atom in the drug with a boron-fluorine compound, boracycle, opens up great opportunities to modify the drug’s properties. In this illustration, the boron-fluorine compound has been replaced with a radioactive iodine compound. Illustration: Henrik Sundén.

No need to break down the drug

Traditionally, introducing new functional molecules into a drug has required incorporating them during the original construction of the compound. Directly replacing a hydrogen atom in a finished drug molecule has not been possible.

Using the new approach, researchers can first replace a hydrogen atom with a BF₂-boracycle. In a subsequent step, the boron compound can be exchanged for a wide range of other molecules that give the drug new properties.

“Our discovery means that you don’t have to take the drug apart to improve it. Instead, you can test perhaps a hundred different functional molecules that easily replace the boron compound to see which molecule best improves the drug,” said Sundén.

Potential for cancer diagnostics

The study demonstrates that the boron compounds can be swapped for many different chemical groups, including halogens, alcohols and azides. They can also be used in important coupling reactions commonly used in medicinal chemistry.

Of particular interest is the method’s ability to introduce radioactive iodine, which is key in cancer diagnosis and treatment. Radioactive iodine is widely used in scintigraphy, an imaging technique in which a gamma camera detects radiation from within the body to reveal abnormal tissue at an early stage.

In tumour diagnostics, scintigraphy is mainly used when bone metastases are suspected, but it is also applied to examinations of the liver, kidneys, thyroid and lymphatic system.

The development was carried out in collaboration with AstraZeneca. For pharmaceutical companies, the ability to fine-tune drugs at a late stage could save both time and resources by avoiding the need to restart development from the very beginning.