Title: Researchers Attain Exacting Control Over Chirality in Interlocked Molecules Utilizing Chiral Anions
In a major advancement for molecular engineering and chirality management, a group of scientists—collaborating closely with the late Nobel Prize winner Sir Fraser Stoddart—has unveiled a groundbreaking technique to manipulate the chirality of mechanically interlocked molecules, or MIMs. By leveraging non-covalent interactions with enantiopure chiral sulfonate anions, the researchers successfully modified the balance between the two mirror-image forms, or enantiomers, of a specifically designed catenane. This pioneering method introduces mechanical chirality without compromising the overall structural integrity of the molecule.
“This breakthrough could drive progress in pharmaceuticals and materials science due to the importance of chirality,” stated Ruihua Zhang, a chemist from the University of Hong Kong and part of the research team. “In contrast to traditional chiral molecules that depend on stereogenic centers, the mechanical chirality of our catenane originates entirely from its interlocked topology.”
Grasping Mechanical Chirality
Chirality—or handedness—is an essential characteristic in both chemistry and biology. It significantly impacts the effectiveness and safety of pharmaceutical compounds, as well as the creation of materials with distinct optical or electronic characteristics. Molecules can exhibit chirality based on atomic configurations (covalent chirality) or, as demonstrated in this research, because of their topology—termed mechanical chirality.
The researchers concentrated on catenanes, which are molecules made up of two or more interlocked rings that cannot be disentangled without disrupting covalent bonds. These molecules show mechanical chirality if their rings are arranged in a non-superimposable mirror image.
An earlier iteration of the catenane was synthesized in 2013, comprising two cyclobis(paraquat-p-phenylene) or CPBQT4+ rings. Due to their symmetrical structure, the initial molecule—designated HC8+—was achiral. By carefully substituting two quaternary nitrogen atoms with neutral carbon atoms, the researchers disturbed the symmetry of the ring to induce chirality.
Compact Configuration Enables Selective Arrangement
According to team member Chun Tang, the closely packed arrangement of the interlocked rings was crucial for controlling the chirality. “The two rings are not just tangled; they are engineered to be compact, minimizing random motion—this compact mechanical bond allows us to accurately control the positioning of the two rings, rendering them chiral,” Tang explained.
The team introduced the term “isostructural desymmetrisation” for their methodology, which describes the incorporation of asymmetry while preserving the overall structure of the molecule. The asymmetric alteration led to uneven charge distribution and steric interactions that promoted the formation of different chiral co-conformations.
Chiral Anions Influence the Equilibrium
As noted by Stephen Goldup, a chemical researcher at the University of Birmingham, the interlocked rings can rotate or adjust in relation to one another, creating two equivalent yet opposite chiral configurations. In the absence of external influences, the molecule manifests as a racemic mixture—equal distributions of both chiral variants.
However, by introducing enantiopure chiral disulfonate ions, the researchers formed diastereomeric ion pairs—non-mirror-image stereoisomers with differing energies. This stability disparity enables one chiral variant to be favored over the other, a situation confirmed through dynamic NMR spectroscopy. The analyses indicated a considerable rotational barrier (16.4 kcal/mol) between the two enantiomers, affirming that the system could be oriented toward a specific configuration.
“When the chiral anion associates with our catenane via electrical attraction and weak intermolecular forces, it preferentially stabilizes one form over the other,” Tang added.
Crystal-State Control and Challenges to Scalability
The researchers demonstrated that while partial chirality control is feasible in solution, total stereoselectivity can currently only be achieved in the crystalline state. During crystallization with chiral sulfonate anions, only one of the diastereomers developed a stable crystal lattice, attributed to more advantageous packing interactions.
“Although mechanically chiral molecules with defined stereochemistry have shown exciting potential applications in areas such as catalysis and chiral emission, achieving enantiopurity is still challenging,” Goldup observed. “This breakthrough presents a clever pathway toward that aim.”
Prospects and Future Applications
This technique for regulating chirality through non-covalent interactions instead of synthetic modification unveils encouraging possibilities across various fields. Mechanically chiral molecules could be employed to create highly specific catalysts, chiral sensors, or photoswitchable materials. Unlike covalently chiral centers, mechanical chirality provides enduring configurational integrity and adaptability.
Researchers connected with the project are hopeful about crafting new families of chiral catenanes and rotaxanes based on similar principles. However, hurdles remain in synthesizing at scale and adapting the technique to alternative molecular structures.
Nevertheless, the discovery marks a sophisticated solution to one