Drug Design Breakthrough: Stable Chiral Molecules Unlock New Possibilities

Scientists Engineer “Handed” Molecules with Unprecedented Stability

A groundbreaking discovery in molecular science promises to revolutionize drug design, offering unparalleled stability and control over life-saving compounds. Researchers have developed a novel class of chiral molecules, overcoming a long-standing challenge in creating medicines that are both effective and safe.

The Chirality Challenge

Chirality, a concept analogous to left and right hands, describes molecules with the same atomic composition but different spatial arrangements. This subtle difference can drastically alter a molecule’s interaction with biological systems, meaning one mirror image might heal while another poisons. Understanding and controlling this asymmetry is paramount for pharmaceutical development.

A Novel Stereogenic Center

A team from the University of Geneva (UNIGE), in collaboration with the University of Pisa, has achieved a significant milestone by creating a new type of stereogenic center. Unlike traditional centers relying on carbon atoms bonded to four different carbon chains, this new design features a central carbon atom surrounded by oxygen and nitrogen atoms. This innovative approach represents a first in chemical science.

“Molecules with this new type of stereogenic center had never before been isolated in a stable form. Their synthesis and characterization mark a major conceptual and experimental breakthrough.”

—Jérôme Lacour, Full Professor, Department of Organic Chemistry, UNIGE Faculty of Science

Exceptional Molecular Stability

The stability of chiral molecules is critical; rapid interconversion between mirror images can render a drug inactive or toxic. The UNIGE team’s newly synthesized molecular structures exhibit remarkable chiral stability, making the transition to their mirror counterparts exceedingly improbable. This enhanced stability ensures safe storage without the need for specialized conditions.

According to doctoral student Olivier Viudes, the initial molecule developed would require an astonishing 84,000 years at room temperature for half of it to transform into its mirror image. For a second molecule synthesized by the team, this transformation time was calculated to be 227 days at 25°C. This level of stability is crucial for reliable drug formulation and shelf life. For comparison, the half-life of some essential pharmaceuticals can be measured in months or years, highlighting the importance of such molecular durability.

Future Prospects in Medicine and Materials

These novel stereogenic centers provide a new avenue for designing three-dimensional chiral molecules with enhanced stability and precise control. This opens up vast opportunities not only in the creation of more effective and safer drugs but also in the development of advanced materials.

“These novel stereogenic centers offer a new way of organizing molecular space. They open up a whole new degree of freedom and imagination in chemical synthesis.”

—Gennaro Pescitelli, Professor, University of Pisa