Supramolecular cages are among the most fascinating structures in modern chemistry. They are constructed from individual molecular building blocks, which self-assemble into three-dimensional architectures. Research into such nanostructures focuses on applications such as molecular reaction chambers, sensors or potential therapeutic drug delivery systems. While their targeted assembly is well understood, selective disassembly still poses a challenge.
This is where the Düsseldorf study, which has now been published in the renowned scientific journal Nature Communications, comes in. The researchers appended flexible polymer chains, i.e. essentially functioning like tiny molecular ropes, to molecular cages based on the chemical element palladium. When these systems are subjected to ultrasound irradiation, the polymer chains transmit mechanical forces into the nanostructure’s scaffold, allowing bonds to be selectively broken and the cages to be opened in a controlled manner. This mechanism is important, e.g. in enabling the targeted delivery of therapeutic drugs in the body.
“Self-assembled molecules are often described as dynamic systems. To date, however, no methods enabling targeted mechanical intervention in these processes have been available. Our work shows that ultrasound can be an extremely effective tool for controlling such nanostructures,” explains Dr Bernd M. Schmidt.
It is particularly worthy of note that the researchers were not only able to observe the disassembly of the structures. Under suitable conditions, they were also able to fully reassemble the activated systems again.
The researchers applied the practical benefits directly in a further focus of the study, namely the controlled release of the anticancer drug cisplatin. First of all, the drug was encapsulated in the molecular containers. The ultrasound irradiation then triggered the selective opening of the drug carriers to enable the release of the medication.
“The release of cisplatin served as a research model, demonstrating that mechanical forces can be used to release molecular freight from inside supramolecular nanostructures in a targeted fashion,” says lead author Tim David. “This opens up interesting long-term perspectives for the development of intelligent transport systems.”
In order to understand the experimental observations at the molecular level, the researchers combined their experiments with advanced computer simulations. The size and complexity of the examined systems posed a particular challenge. Depending on the architecture, the solvated structures comprise between several hundred and more than 4,000 atoms. The interaction between these atoms must be calculated with a high degree of accuracy in order to ensure the bond breakages induced by the mechanical force are depicted correctly. Conventional simulation methods quickly reach their limits here: Either too much computing power is needed for such large systems or the methods simply cannot depict the bond breakages accurately enough.
Consequently, the team headed by Professor Jan Meisner used a special machine-learning interatomic potential, which they optimised explicitly for the description of metal-ligand bonds. This enabled the realisation of simulations, which are much quicker than conventional quantum chemical calculations, yet can depict the chemical reactions with virtually the same degree of accuracy. As a result, the researchers were able to ascertain the forces at which individual palladium-nitrogen bonds break and the process of cage disassembly under mechanical stress.
“The new simulations enabled us to establish which forces are needed to break individual bonds within the cages,” explains Professor Jan Meisner. “This gives us a direct insight into processes, which are virtually impossible to observe experimentally. The use of machine learning allowed us to simulate large and complex systems efficiently and examine the mechanochemically induced reactivity.”
The study thus offers fundamental insights into how mechanical forces can be transmitted through supramolecular systems. At the same time, it opens up new possibilities for the development of adaptive materials, switchable molecular systems and future drug delivery systems.
The study was conducted at the Institute of Organic Chemistry and Macromolecular Chemistry and the Institute of Physical Chemistry at HHU.
Nature Communications
Experimental study
Cells
Mechanochemical disassembly pathways of self-assembled polymer-decorated PdnL2n supramolecular architectures
19-Jun-2026