As the size and complexity of solution-synthesized molecules increase dramatically, single-crystal X-ray diffraction remains capable of determining absolute configuration and atomic positions. However, macromolecules often require solubilizing groups due to poor solubility, which complicates crystal growth. Scanning tunneling microscopy (STM) enables single-molecule imaging, and when combined with scanning tunneling spectroscopy (STS), it can reveal electronic states and orbital distributions. Nevertheless, STM imposes stringent requirements on sample cleanliness and molecular planarity, and macromolecules are difficult to thermally sublimate. There is an urgent need to develop STM sample preparation techniques tailored to macromolecules to support structural and property characterization.

The rules governing knotting in polymer chains have long lacked a clear understanding: the knotting mode, knot type, knot position along the chain, and their effects on physicochemical properties all remain unclear. Although theoretical simulations have a history of nearly 60 years, experimental approaches for the precise and efficient construction of molecular knots and their direct observation have yet to be effectively achieved. The precise construction and atomic-scale characterization of molecular knots are key to addressing this issue, and current technical bottlenecks are driving the synergistic innovation of sample preparation and imaging methods.

Recently, the team of Xiaopeng Li and Zhi Chen together with Zhang Liang from Fudan University/East China Normal University, Dai Liang from City University of Hong Kong, and David A. Leigh from the University of Manchester, published a research paper in Nature Chemistry titled “Trefoil polymers from a knotted synthon” (DOI: 10.1038/s41557-026-02197-4). The paper develops a polymer construction strategy based on a “knot synthon”. Using this strategy, trefoil-knotted polymers, cyclic topological isomers, and their corresponding linear polymers were constructed precisely and efficiently, with polymer segments including polystyrene (PS), polyethylene glycol (PEG), and block copolymers (PS-PEG). The thermal properties, solution behavior, and surface conformation distribution of the topological structures were systematically analyzed. Relying on high-resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and low-temperature ultrahigh-vacuum scanning tunneling microscopy (UHV-LT-STM), the trefoil-knotted polymer structures were precisely characterized, and direct imaging observation of their three topological conformations was achieved for the first time (Figure 1). Combined with surface statistical analysis and coarse-grained simulations, the study revealed the physical mechanism underlying the stability differences among the different conformations. The success of this work not only opens a general route for synthesizing polymer materials with precisely defined topological structures but also, for the first time, unveils the conformational behavior and influencing factors of polymer knots at the single-molecule level.

Figure 1. Structures of trefoil-knotted polymers and their STM imaging.

Link: https://www.nature.com/articles/s41557-026-02197-4

In the field of precision macromolecular synthesis and characterization, the team of Xiaopeng Li and Zhi Chen in collaboration with Wang Tao from the Shanghai Institute of Organic Chemistry, recently published a paper in J. Am. Chem. Soc. entitled “Resolving Solution-Synthesized Graphyne-Graphdiyne Macromolecules at the Angstrom Level” (J. Am. Chem. Soc. 2026, 148, 15873). In this work, a modular strategy was employed to synthesize a series of discrete coaxial macrocycles based on Graphyne-Graphdiyne hybrids, covering the C5-C8 range. The authors combined electrospray ionization with scanning tunneling microscopy (ESISTM) to achieve highly pure and efficient vacuum deposition of solution-synthesized macromolecules. Furthermore, they developed single-molecule tip manipulation and bromine-assisted thermal treatment methods to remove the three-dimensional solubilizing alkoxy/alkyl chains introduced during solution synthesis, thereby promoting molecular planarization. This enabled chemical bondresolved structural imaging and angstromlevel visualization of frontier molecular orbitals for this series of covalent coaxial macrocycles. This approach resolves the long-standing conflict between the solubility requirements of solution synthesis and the planarization demands for high-resolution STM characterization, pushing the imaging resolution of complex solution-synthesized macromolecules to the angstrom scale (Figure 2).

Figure 2. Synthesis of discrete Graphyne-Graphdiyne macrocycles and their STM structural imaging with chemical bond resolution.

Link: https://pubs.acs.org/doi/10.1021/jacs.5c22800

The above works were supported by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, and the Shenzhen Science and Technology Innovation Program.

The research group has long been engaged in research in the fields of supramolecular chemistry, rare-earth crystalline materials, surface physical chemistry, and mass spectrometry characterization. They have gained broad influence in supramolecular chemistry and mass spectrometry. The research group has deep expertise in STM characterization of solution-synthesized supramolecules and polymers and has explored a series of sample preparation methods, including solution drop-casting, electrospray deposition, and flash evaporation, which are applicable to the diverse characterization needs of different supramolecular and polymeric systems. Welcome undergraduate students, master's students, doctoral candidates, and postdoctoral researchers who are interested in supramolecular self-assembly, synthesis and application of functional macromolecules, and single-molecule STM characterization to join the research group (Email: zhi.chen@szu.edu.cn).