Innovative clip-off chemistry enables fast and precise production of complex molecules

Researchers at the ICN2 and the UAB have developed a novel strategy to obtain different types of organic molecules by breaking down their molecular structures. This technique enables fast and precise production of these molecules without having to use traditional chemical synthesis. The results pave the way for simple and efficient production of complex molecules, with promising applications in areas such as the development of new materials.

The study introduces a method of extracting macrocycles, which are cyclic organic molecules that are already used in several industries, such as food, cosmetics, and drug delivery. To obtain them, the team started with larger porous crystalline structures called COFs (covalent organic frameworks), which contained the desired macrocycles within their molecular framework. COFs are widely studied molecules due to their potential applications in areas such as gas storage and chemical separation processes.

The work, published in the journal Science, is the result of an international collaboration involving researchers from several institutions, including the Universitat Autònoma de Barcelona (UAB), the University of Girona, the University of California, Berkeley, and the Institute of Materials Science of Barcelona (ICMAB-CSIC).

Clip-off chemistry: The art of ‘cutting out’ molecules

The technique is based on the concept of Clip-off Chemistry, developed under the leadership of ICREA Professor Daniel Maspoch, head of the ICN2 Supramolecular NanoChemistry and Materials Group, researcher in the UAB Department of Chemistry, and lead author of the study. This strategy relies on materials that already incorporate the target molecules within their structure, which are then selectively “clipped off” and released.

The COFs used in the study were designed in advance using simple molecular precursors, with specific chemical bonds incorporated at strategic positions, such as double and triple bonds between carbon atoms which can be selectively broken.

Once the COFs had been synthesized, the next step was to release the macrocycles. To achieve this, the researchers employed ozone gas as a molecular “scalpel.” This gas is made up of three oxygen atoms and can break these reactive bonds through a process known as ozonolysis. This releases the macrocycles quickly and efficiently, eliminating the need for slow and complex synthesis routes.

As Prof Maspoch explains, “We design materials that already contain the rings we’re aiming for, using simple building blocks—like LEGO pieces—and then we release them with surgical precision.”

Enormous potential across fields

Using this strategy, the researchers successfully synthesized nine different types of macrocycles, some of which contained up to 162 atoms. These included several chemical structures and various functional groups, such as aldehydes and carboxylic acids, which demonstrates the technique’s versatility.

The resulting macrocycles’ structure was confirmed using advanced techniques such as mass spectrometry and scanning tunneling microscopy. Significant contributions to these analyses were made by the ICN2 Atomic Manipulation and Spectroscopy Group, led by ICREA Professor Aitor Mugarza.

According to the authors, “This method paves the way for a new and versatile approach to obtaining complex molecules. It has enormous potential for use in diverse fields such as organic chemistry, nanotechnology, and the development of new materials, devices, biosensors, etc.”