Professor Jiawen Chen and Associate Researcher Yan Wang from South China Normal University, in collaboration with Professor Ben L. Feringa's team at the University of Groningen, Netherlands, designed a novel molecular machine with both rotational and shuttle motion modes. This molecular machine combines a sterically hindered olefin molecular motor, an H-type benzimidazole, and a crown ether system, achieving for the first time the control of rotaxane shuttle motion through the rotational motion of the molecular motor. The motion mechanism of this molecule was elucidated in detail using methods including two-dimensional proton NMR spectroscopy and theoretical calculations. This work demonstrates the tuning effect of two different motion modes within a single molecular machine, providing a solid experimental foundation for the future design of multifunctional molecular machines with complex mechanical functions. The article was published as an open access Research Article in CCS Chemistry, the flagship journal of the Chinese Chemical Society.
Background information:
Artificial molecular machines driven by external stimuli can achieve controllable directional motion and are a core foundation for building intelligent response systems. Through chemical synthesis, scientists simulate macroscopic mechanical motion, achieving non-equilibrium behavior at the molecular level, driving development in several emerging directions, from artificial muscles and adaptive materials to bio-hybrid systems. The pioneering research of Nobel laureates Stoddart, Sauvage, and Feringa, among others, has propelled the design and application of typical molecular machines such as rotaxanes, sesquiterpenes, and molecular motors. Current research challenges in this field lie in integrating different types of molecular machines into the same system to achieve synergistic motion and functional enhancement.
Highlights of this article:
In this study, three dumbbell-shaped guest molecules (1a, 1b, 1c) containing molecular motors with different rotational speeds were designed and synthesized, and assembled with the flexible macrocyclic crown ether B36C10 to obtain rotaxane [2]. At room temperature, the crown ether B36C10 can perform continuous complexation-decomplexation shuttle motion between the two sets of benzimidazole units of the guest molecule. Since each shuttle must pass through the structurally asymmetric motor rotor, the shuttle rate between the recognition sites on both sides of the ring unit is different, resulting in uneven conformational distribution.
To analyze this asymmetric kinetic behavior, the authors employed 2D-NOESY analysis. They differentiated the chemical shift differences between c and d by the spatial shielding effect of the naphthalene ring on proton c. Combined with the chemical shift changes of the NH group in complexed/non-complexed states, they confirmed that when the crown ether is located at the recognition point on one side of the naphthalene ring, the [1a⊂(B36C10)]-Nap conformation is the dominant conformation of the system (Figure 2). After conformational identification, the authors further analyzed the shuttle motion rate using two-dimensional chemical exchange spectroscopy (2D EXSY): the motion of the ring unit from the recognition point on the naphthalene ring side to the recognition point on the methyl side was defined as k-1 (velocity 2.12 s⁻¹), and vice versa as k1 (velocity 2.97 s⁻¹). Under 365 nm ultraviolet light irradiation, the molecular motor rotor in the [1a⊂(B36C10)] system enters a photoisomerization metastable state, forming a meta-stable [1a⊂(B36C10)]. At this point, the crown ether preferentially resides at the recognition site on the methyl side, and the corresponding meta-stable [1a⊂(B36C10)]-Me conformation becomes the dominant conformation of the system. The motion rate of the ring units increases (k-1 = 4.55 s⁻¹, k1= 3.73 s⁻¹). After heating, the molecular motor rotor can return to its initial stable state, fully demonstrating the highly reversible nature of the photothermal stimulation in regulating the shuttle motion within the system. The system remains stable after more than 20 alternating photothermal signal inputs, without significant performance degradation.
To investigate the differences in the preferential localization of crown ethers in stable and meta-stable [1a⊂(B36C10)] , and the mechanism of bidirectional shuttle acceleration in the meta-stable state, this study conducted systematic multi-scale computational simulations (Figure 3). DFT combined with IGMH analysis showed that in the stable state, there is a stronger non-covalent interaction between the crown ether and the naphthalene site (-45.43 vs -38.84 kcal/mol), while in the meta-stable state, the interaction advantage is reversed to the methyl site (-38.15 vs -30.69 kcal/mol), resulting in a change in the preferential shuttle direction.
Meta-dynamic simulations show that the shuttle energy barrier is lower in the meta-stable state (2.5/1.8 vs. approximately 3 kcal/mol), and the free energy surface splits into multiple minima, promoting rapid shuttle movement of the crown ether through conformational adjustment. Trajectory analysis further reveals that the synergistic motion of the upper and lower halves of the motor is significantly enhanced in the meta-stable state, and the π-π/CH-π interaction between the crown ether and the rotor is stronger, jointly driving the acceleration of the shuttle motion.
Based on [1a⊂(B36C10)], the authors further constructed [1b⊂(B36C10)] and [1c⊂(B36C10)] by adjusting the motor speed. Compared with [1a⊂(B36C10)] (speed 4.4×10⁻⁸ r/s ), which is almost in a static deformation state, [1b⊂(B36C10)] (0.019 r/s) and [1c⊂(B36C10)] (4.6×10⁵ r/s) have higher speeds, thus allowing observation of the influence of rotor dynamic deformation on shuttle motion.
When the motor speed approaches the shuttle rate ([1b⊂(B36C10)]), the motor continues to rotate under illumination, and the NMR spectrum shows the coexistence of multiple conformations. At this time, the average shuttle speed increases to twice the original value (Figure 4). After the illumination stops, the structure returns to its initial state in a short time. When the speed is much higher than the shuttle rate ([1c⊂(B36C10)]) , the motor rotation does not affect the shuttle behavior. This may be because the metastable state exists for a very short time and fails to significantly change the shuttle energy barrier.
Summary and Outlook:
To control complex motions at the nanoscale, this study designed three molecular machines with shuttle and rotational motion modes. By combining a light-driven molecular motor unit and a rotaxane shuttle system, the authors demonstrated that the shuttle direction and speed of the rings in rotaxane can be adjusted by motor rotation, and the entire process is completely reversible. Experimental data show that motor rotation significantly accelerates ring shuttle and alters their dominant position during the shuttle process. DFT calculations of stable and meta-stable coconformations reveal that the π-π non-covalent interaction between the crown ether and the motor unit determines the preferred position of the macrocycle. Further molecular dynamics simulations reveal that when the motor rotates, the rotor motion reduces steric hindrance and enhances the non-covalent interaction between it and the shuttle ring, thereby increasing the shuttle speed. Notably, as the motor rotation speed increases significantly, its influence on the ring shuttle motion gradually disappears. This study elucidates how to utilize external energy input to achieve the regulation of coupled motion, providing important insights for the design of future multifunctional molecular machines.
This work was published as a Research Article in CCS Chemistry. The first author is Shilong Zhang, a doctoral student at the South China Institute of Advanced Optoelectronics, South China Normal University. Professor Jiawen Chen and Associate Researcher Yan Wang from South China Normal University and Professor Ben L. Feringa from the University of Groningen are the co-corresponding authors. This research was generously supported by the National Key Research and Development Program of China, the Guangzhou Science and Technology Project, the Guangdong Provincial Key Laboratory of Optical Information Materials and Technology, the Gravity Program of the Netherlands Ministry of Education, Culture and Science, and the China Postdoctoral Science Foundation.
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About the journal: CCS Chemistry is the Chinese Chemical Society's flagship publication, established to serve as the preeminent international chemistry journal published in China. It is an English language journal that covers all areas of chemistry and the chemical sciences, including groundbreaking concepts, mechanisms, methods, materials, reactions, and applications. All articles are diamond open access, with no fees for authors or readers. More information can be found at https://www.chinesechemsoc.org/journal/ccschem .
About the Chinese Chemical Society: The Chinese Chemical Society (CCS) is an academic organization formed by Chinese chemists of their own accord with the purpose of uniting Chinese chemists at home and abroad to promote the development of chemistry in China. The CCS was founded during a meeting of preeminent chemists in Nanjing on August 4, 1932. It currently has more than 120,000 individual members and 184 organizational members. There are 7 Divisions covering the major areas of chemistry: physical, inorganic, organic, polymer, analytical, applied and chemical education, as well as 31 Commissions, including catalysis, computational chemistry, photochemistry, electrochemistry, organic solid chemistry, environmental chemistry, and many other sub-fields of the chemical sciences. The CCS also has 10 committees, including the Woman's Chemists Committee and Young Chemists Committee. More information can be found at https://www.chinesechemsoc.org/ .
