Small molecule drugs for tumor and genetic disease treatments

26.08.2024

A research team led by the University of Padua has published the paper Radical strain-release photocatalysis for the synthesis of azetidines in Nature Catalysis. The work focuses on the developing a method for the synthesis of azetidines, which plays an important structures present in various drugs. Its unique biologically active compound has the potential to treat cancer and genetic pathologies.

Given its complex structure, the study offers an important step towards new horizons in the sustainable construction of such molecules.

“In this study, we present a new strategy that uses simple sunlight to simply and sustainably create azetidines– explains Luca Dell’Amico, from the Department of Chemical Sciences of the University of Padua and corresponding research author -. This method uses an organic photosensitizer, which is a molecule capable of activating the components of the chemical reaction, making them react together through a strain release approach. To clarify, it is as if light were used to stretch a rope, and in our case, it is used to stretch the atoms of the molecules until they reach the desired reactivity. Using only light, no waste products are generated, furthermore, light is an abundant and zero-cost reagent for us.”

The work of the research team demonstrates how it is possible to arrive at azetidine structures with high biological activity using renewable energy sources and in a simple way. 

The growing popularity of small organic molecules in drug discovery has prompted chemists to develop new strategies to create these structures. Recently, a method called "strain release" has been used to build new bioactive molecules. Strain release refers to the ability to make compounds that have high energy react due to the tension created between their component atoms, a bit like when you stretch a string to the extreme. 

As soon as we bring a blade, or in our case, a molecule, close to it, the string breaks and the molecule likewise reacts by breaking a bond and forming a new one. However, while there are many ways to create small carbon-based rings, the synthesis of azetidines, which are like rings but contain nitrogen, is still underdeveloped.