Researchers at the University of Jyväskylä, Finland, have developed a new strategy for programming synthetic molecules to self-assemble into precisely defined three-dimensional structures. The study brings scientists a step closer to achieving the sophisticated molecular organization found in nature and could eventually open new possibilities for the development of advanced functional materials.

In living organisms, molecules such as proteins reliably fold into specific shapes according to information encoded in their molecular sequences. Replicating this level of structural control in synthetic systems has remained a major challenge.

Now, researchers at the University of Jyväskylä have shown that multiple layers of information can be encoded within an artificial molecule to control how it assembles. In the study, the molecules selectively formed a triple helix, in which three molecular strands wind around one another in an anticlockwise direction. At the same time, the formation of competing structures was effectively suppressed.

Encoded information determines the final structure

The approach, termed hierarchical sequence control, operates in two stages. The first layer of information performs an initial selection, restricting the possible outcomes of the assembly process to four types of helices. The second layer provides an additional level of selection, favouring the formation of one specific helix among these four: the anticlockwise triple helix.

- The key is that by fine-tuning the molecular sequence, we can precisely control which three-dimensional structure ultimately forms. We found that careful sequence optimization is crucial for achieving this high level of structural control, says Professor Fabien Cougnon from the University of Jyväskylä, who led the study.

Towards programmable molecules and advanced materials

The study marks a step towards synthetic molecules that can translate encoded sequence information into complex three-dimensional structures in a predictable way, resembling the highly controlled molecular organization found in nature.

- Our long-term goal is to design molecules whose structures can be predicted and controlled with increasing precision. Programmable molecular self-assembly could eventually open new opportunities for developing smart materials, molecular devices and other advanced technologies, Cougnon says.

The results have been published in the Angewandte Chemie International Edition journal.