Atomic imaging of intermolecular interactions is of great significance for a deep understanding of the fundamental physical and chemical principles in various application fields. However, the inherent thermal mobility of molecules and their beam sensitivity pose great challenges to capturing individual molecules and achieving high-resolution observation. Currently, a variety of confinement methods can "freeze" the configurations of small molecules，such as surface adsorption and cryogenic environments. Nevertheless, it should not be overlooked that these imaging methods have significant technical limitations, and there is an urgent need for new methods to realize the imaging and characterization of confined molecules and their interactions at room temperature or higher. Although the electron microscope is regarded as a powerful tool for atomic structure analysis, the fact that small molecules are highly susceptible to damage from high-energy electron irradiation, which has become a key factor hindering the development of molecular imaging. In recent years, low-dose electron microscopy imaging has achieved significant breakthroughs and been widely applied to study electron-sensitive materials. Combining the confinement effects with the low-dose imaging method provides an effective way to achieve stable high-resolution analysis of molecules and their interactions.
Recently, Associate Researcher Bin Song and Professor Boyuan Shen from the Institute of Functional Nano & Soft Materials (FUNSOM) at Soochow University, together with their collaborative teams, conducted imaging analyses on three different confinement systems, including the perovskite system (ionic interactions), the zeolite/aromatic molecule system (van der Waals interactions), and the metal-organic framework system (coordination interactions). They innovatively proposed an universal strategy for molecular imaging, which combines the low-dose imaging technology (represented by the integrated differential phase contrast technology) with the enhanced confinement effects, and successfully achieved high-resolution imaging and analysis of the structures and interactions of molecules (ions). Furthermore, they set the aspect ratio of the molecular images as a key parameter to evaluate the strength of the host-guest interactions in the three material systems. By changing the guest molecules, they deeply analyzed the influence of the strength of each interaction on the imaging quality of these molecules imaging. In the perovskite and zeolite/aromatic molecule systems, clear images of the configurations and orientations of molecules (ions) can be obtained by enhancing the host-guest interactions. In the metal-organic framework system, it is even possible to accurately analyze the atomic-scale structure of aromatic molecules and the length of coordination bonds. These research results provide a universal description of the relationship between molecular imaging and interactions, offer new possibilities for exploring the mechanisms of molecular behavior in more application scenarios through real-space imaging. The relevant achievements were published in the journal Nature Communications (DOI: 10.1038/s41467-025-57816-4).
Figure. The strategy for imaging molecular structures by enhancing confinements.
Link to paper: https://www.nature.com/articles/s41467-025-57816-4
Title: Imaging molecular structures and interactions by enhanced confinement effect in electron microscopy
Authors: Mengmeng Ma#, Qinnan Yu#, Jiayi Zhang, Xiao Chen*, Wenbo Li, Xianlin Qu, Xuliang Zhang, Jiale Feng, Fei Wei, Jianyu Yuan, Tao Cheng, Sheng Dai, Yi Wang*, Bin Song*, Boyuan Shen*
Link to Prof. Boyuan Shen: https://funsom.suda.edu.cn/ee/df/c2735a454367/page.htm
Editor: Guo Jia