DNA, or deoxyribonucleic acid, is the molecular foundation that carries genetic information in living organisms, using its double helix structure to transcribe and amplify this information. Scientists are keen on developing artificial molecular systems that can rival or even surpass the functionality of DNA. Among these systems, double-helical foldamers stand out as promising candidates.

Helical foldamers are synthetic molecules designed to fold into well-defined helical structures, similar to those found in proteins and nucleic acids. These molecules have gained attention for their potential as stimuli-responsive materials, tunable chiral systems, and cooperative supramolecular structures due to their unique chiral and conformational switching properties. Double-helical foldamers, in particular, exhibit enhanced chiral properties and the ability to transmit chiral information from one strand to another, opening the door to applications in replication-like processes found in nucleic acids. However, controlling the chiral switching of these artificial molecules has been challenging, due to the need for a delicate balance between stability and dynamic properties.

In a recent breakthrough, a team of researchers from Tokyo University of Science, Japan, led by Professor Hidetoshi Kawai, developed a novel class of double-helical molecules called monometallofoldamers, with controllable chiral switching capabilities. “In this research, we succeeded in synthesizing a double helical mononuclear complex, bridged with a single metal cation at the center of the helices, balancing both stability and dynamic properties,” explained Prof. Kawai. Their findings were published in the Journal of the American Chemical Society on July 19, 2024.

The researchers created the double-helical monometallofoldamers using two bipyridine-type strands with L-shaped units. When these strands formed a complex with a zinc cation, they developed into double-helical structures, as confirmed by X-ray crystallography. The team explored the switchability of these monometallofoldamers in response to external stimuli. They discovered that the helices could unfold into an open form in solutions at high temperatures and refold into the double-helical form at lower temperatures.

Interestingly, the helicity of the double-helical monometallofoldamers could be controlled by the type of solvent used. In non-polar solvents like toluene, hexane, and diethyl ether (Et2O), the helices adopted a left-handed or M-form. In contrast, in Lewis basic solvents such as acetone and dimethyl sulfoxide (DMSO), the helices switched to a right-handed or P-form. The presence of chiral chains within the helix strands was crucial for this M/P switching. Furthermore, when a chiral helix strand was mixed with an achiral strand, the chiral information was transmitted and amplified to the achiral strand, maintaining the helicity inversion ability.

Highlighting the significance of this discovery, Mr. Kotaro Matsumura, a key researcher on the team, noted, “Our synthesized double-helical monometallofoldamers have the potential to be applied in developing new chiral materials that can produce diverse chiral properties with minimal input. These materials could be used to create chiral sensors and other advanced applications. Additionally, we anticipate that this novel molecular structure will inspire the development of deracemized and organized supramolecular systems, similar to those found in nature, by transmitting and amplifying their superior chiral properties.”

This study represents a significant advance in the creation of controllable artificial double-helical structures, paving the way for the development of novel high-order molecular systems and molecular information processing technologies.

By Impact Lab