Controllable chiral switching in double helical foldamers for advanced molecular systems

Deoxyribonucleic acid, or DNA, the molecular structure that carries the genetic information of organisms, uses its two helical strands to transcribe and amplify information. Creating such synthetic molecular systems that match or surpass DNA in function is of great interest to scientists. Double helical foldamers are one such molecular structure.

Helical foldamers are a class of synthetic molecules that fold into well-defined helical structures similar to the helices found in proteins and nucleic acids. They have received considerable attention due to their chiral and conformational switching properties as stimuli-responsive switchable molecules, tunable chiral materials, and cooperative supramolecular systems. Double-helical foldamers exhibit not only strong chiral properties but also unique properties, such as transcription of chiral information from one chiral strand to another without chiral properties, enabling potential applications in higher-order structural control of replication-related materials such as nucleic acids. However, synthetic control of the chiral switching properties of such synthetic molecules remains challenging due to the difficulty in balancing the dynamic properties required for switching and stability. Although various helical molecules have been developed in the past, reversal of twist direction in double-helix molecules and supramolecules has rarely been reported.

As a breakthrough, a team of researchers from Japan’s Tokyo University of Science, led by Professor Hidetoshi Kawai from the Faculty of Science, Department of Chemistry, and Mr. Including Kotaro Matsumura, they developed a new mechanical motif. Double helical monometallofoldamers with controllable chiral switching. Professor Kawai explains, “In this research, we succeeded in synthesizing a double helical mononuclear complex anchored by a single metal cation at the center of the helices to balance both stability and dynamic properties. These structures can undergo reversibility by changing the left and right twist directions of the helix strands using different solvents..” Their study was published Journal of the American Chemical Society On July 19, 2024.

The researchers synthesized double-helical monometallofoldamers with L-shaped units from two bipyridine-type strands, which formed double-helical structures after forming a complex with a zinc cation. X-ray crystallography revealed double helical structures with a metal cation at their core. The researchers investigated the switching of monometallofoldamers in response to external stimuli and found that the helix terminals of the double-helical form expand in solutions, resulting in an open form favored at higher temperatures and a double-helical form favored. Low temperature.

Interestingly, the helicity of a double-helical monometallofoldamer containing chiral chains can be controlled in response to achiral solvents. For example, in non-polar solvents (toluene, hexane, etc₂O), it is left-handed or Mform, and in Lewis basic solvents (acetone, DMSO), it is right-handed or B– Shape. The conformation of the chiral chains introduced into the helix strands was found to be critical for this M/P switching. Furthermore, they found that when mixing a helix strand with chiral chains with a strand without chiral chains, the twisting direction of the helix is ​​transmitted to the achiral strand without chiral chains and the helicity reversibility is maintained.

Emphasizing the importance of this new molecule, Mr. Matsumura says, “Our synthesized double helical monometallofoldamers have the potential to be used for novel switching chiral materials that exhibit variable chiral properties with small inputs and can be used to develop chiral sensors. Additionally, we expect this novel molecular structure to facilitate the emergence of disordered and ordered supramolecular systems found in nature by conveying and amplifying their superior chiral properties.„

Overall, this study represents a significant step toward the creation of synthetic controllable double helical structures, which paves the way for novel higher-order molecular systems and molecular information processing.