New class of chiral molecules offers strong stability for drug development

Molecules known as chiral are mirror images of one another. Like a right and left hand, two molecules can have the same composition but a different shape and arrangement in space – a difference that can change everything. Understanding and controlling this is crucial in drug design.

Now, researchers at the University of Geneva (UNIGE), in collaboration with the University of Pisa, have developed a new class of stable chiral molecules – an achievement that could transform how drugs are engineered and stored. Their findings have been published in the Journal of the American Chemical Society.

What is chirality – and why does it matter?

A molecule, or any object, is said to be chiral if it cannot be superimposed on its mirror image by any combination of rotations, translations or geometric changes.

This subtle but crucial asymmetry – known as chirality – is a universal feature in molecules and plays a crucial role in how they interact with living organisms. For chemists, designing chiral molecules with precise control is key to ensuring the efficacy and safety of drugs.

A world first: oxygen and nitrogen-centred chirality

Chirality typically stems from so-called “stereogenic centres”, which are often carbon atoms bonded to four different groups or atoms. But the team led by Jérôme Lacour, Professor in the Department of Organic Chemistry at UNIGE’s Faculty of Science, has introduced a completely new approach.

His group has developed a new type of stereogenic centre – one based entirely on oxygen and nitrogen atoms rather than carbon chains.

“Molecules with this new type of stereogenic centre had never been isolated in a stable form. Their synthesis and characterisation mark a major conceptual and experimental breakthrough,” explains Lacour.

Stability that stands the test of time

One of the major challenges in working with chiral molecules is their tendency to “flip” – transforming from one mirror image into the other, usually under heat or over time. This switching can turn an effective medicine into an inactive or even toxic compound.

But the new molecules developed by the UNIGE team show real chiral stability.

“Using dynamic chromatography techniques and quantum chemistry calculations, we have shown that, for the first molecule developed, it would take 84,000 years at room temperature for half a sample to transform into its mirror molecule,” explains Olivier Viudes, PhD student and first author of the study.

In practical terms, that means these molecules would remain stable over human-relevant timescales without needing special storage conditions. For a second molecule in the study, the mirror switch would take 227 days at 25 degrees – still extraordinarily stable by pharmaceutical standards.

Opening new doors in drug and material design

These new stereogenic centres provide chemists with powerful tools to precisely design 3D molecules with long-term stability. Their structure makes them promising candidates not only in pharmaceuticals but also in the development of advanced materials.

“These novel stereogenic centres offer a new way of organising molecular space. They open a whole new degree of freedom and imagination in chemical synthesis,” concludes Gennaro Pescitelli, professor at the University of Pisa and co-principal investigator of the article.

The future of chirality in chemistry

With the successful synthesis of these new and highly stable chiral molecules, the research could lead to safer, longer-lasting drugs. As scientists continue to solve the complexities of chirality, the ability to shape and lock molecules in precise geometries may offer a new level of control in medicine.