A new strategy for assembling π-conjugated panels into square molecules revealed

A new strategy for assembling π-conjugated panels into square molecules revealed Gaby Clark Scientific Editor Alexander Pol Deputy Editor A research group has developed a new method for selectively synthesizing three-dimensional macrocycles,⁽¹⁾ in which four panels are arranged in a square, by connecting planar π-conjugated molecules⁽²⁾ at right angles. This method is applicable to a wide variety of π-conjugated molecules and allows the size of the internal cavity to be designed. Furthermore, the resulting square macrocycles exhibit acid responsiveness, reversibly changing color under the action of a mild acid, while acid-mediated hydrolysis enables the starting monomers to be recovered in high yield—realizing a sustainable molecular synthesis that reverts to and regenerates the starting materials. The originality of this work lies in having a single imine bond play three roles: creating the shape, responding to stimuli and reverting back. These research results were published in the Journal of the American Chemical Society on Monday, June 1, 2026. The team includes Associate Professor Yasutomo Segawa and Assistant Professor Takashi Harimoto at the Institute for Molecular Science (National Institutes of Natural Sciences) and the Graduate University for Advanced Studies (SOKENDAI). Research background Three-dimensional macrocycles, in which planar π-conjugated molecules stand in a ringlike arrangement and are connected to one another, are attracting worldwide attention as functional molecules expected to find applications across a broad range of fields—including organic electronics, molecular recognition and catalysis—owing to their distinctive structures, which possess an internal cavity. Most of the three-dimensional π-conjugated macrocycles synthesized to date adopt nearly circular shapes because the structural strain is distributed evenly throughout the entire molecule. To create polygonal structures, a molecular design that relieves the strain at specific positions is required. In a triangle, the angle between adjacent panels is 60°, and because this angle can be produced from the natural bond angle (approximately 120°) between the sp2 elements that make up planar molecules, triangular macrocycles have been relatively easy to synthesize. A square, on the other hand, which consists of four sides and four corners, requires producing an angle of approximately 90° between adjacent panels—a value that deviates from the natural bond angle—and its synthesis has long been a challenge. In recent years, pioneering synthetic methods using bent molecular frameworks as linkers have been reported. However, many issues remained, such as reduced yields due to side reactions, deformation away from the square structure and the limited range of applicable π-conjugated molecules. Moreover, because these macrocycles are synthesized through irreversible carbon–carbon bond formation, recovering and reusing the starting materials from byproducts is difficult, and improvements have also been called for from the standpoint of resource efficiency. Research results The research group focused on the dibenzo[b,f][1,5]diazocine (DBDA) framework, in which an eight-membered ring (a ring composed of eight atoms) contained within the molecule folds into a boat shape to generate an angle of approximately 90°. By employing this framework as a right-angle linker, they devised a new molecular design strategy that assembles macrocycles in which four π-conjugated panels are arranged in a square. Quantum chemical (density-functional-theory) calculations predicted that the tetramer bearing four DBDA units would adopt the desired square structure and, in addition, would be the most stable compared with other oligomers. The synthesis of the macrocycles was carried out using, as the key reaction, an imine bond formation reaction in which the amino groups (NH₂) and carbonyl groups (C=O) of the monomers combine under acidic conditions. As a result, a square macrocycle with benzene as the π-conjugated panels was successfully synthesized in a high yield of 60% as a mixture of diastereomers differing in the orientation of the DBDA units. Further purification allowed a single diastereomer to be isolated, and single-crystal X-ray diffraction analysis confirmed that it adopted the expected square structure with the planarity of the π-conjugated panels maintained. This is a groundbreaking achievement that greatly improved the synthetic efficiency of square macrocycles, which conventional methods had been limited to producing at low yields due to side reactions. This method is applicable to molecules bearing one benzene ring per side (cycB1₄) as well as molecules containing diverse π-conjugated units such as two benzene rings (cycB2₄), three (cycB3₄) and even pyrene rings (cycP1₄), demonstrating that it is a versatile synthetic strategy in which the size of the internal cavity can be systematically varied. Spectroscopic measurements demonstrated that the obtained macrocycles possess reversible acid responsiveness: Upon addition of an acid (trifluoroacetic acid), the imine bonds react with the acid and the color changes from colorless to yellow-orange, returning to colorless upon neutralization with a base. Furthermore, it was found that when the mixture of oligomers (byproducts) generated in the reaction was treated in a mixed solvent of an organic solvent and an acidic aqueous solution, the imine bonds were hydrolyzed and the starting monomers could be recovered in high yields of 85%–93%. This is a groundbreaking feature that enables regeneration into the starting monomers—something that could not be achieved with conventional syntheses based on the irreversible formation of carbon–carbon bonds. The key point of this study is that a single type of bond (the imine bond) is made to play three roles: synthesis, physical properties and reuse. By harnessing imine bond formation for the efficient construction of the right-angle linker, the researchers achieved shape control; by exploiting the reaction with acid for a reversible color change, they achieved acid responsiveness; and by exploiting bond cleavage under acidic conditions containing water, they achieved recyclability. Future prospects and social significance of this research This method is a synthetic strategy that produces near-right angles using only the sp2 elements that constitute π-conjugated molecules, and a major feature is that it requires neither metallic elements nor sp3 elements. In addition, because the starting materials can be recovered through hydrolysis of the byproducts, it can be regarded as a resource-efficient synthetic method. This strategy can be extended beyond squares to the precise synthesis of π-conjugated molecules with a variety of three-dimensional structures. The obtained family of compounds possesses internal space and acid responsiveness, and is expected to serve as a new platform that deepens our understanding of the structure–property relationships of π-conjugated macrocycles, thereby contributing to the advancement of synthetic organic chemistry and materials science. Publication details Takashi Harimoto et al, Construction of Shape-Persistent All-sp 2 Square Macrocycles via the Formation of Multiple Imine Bonds, Journal of the American Chemical Society (2026). DOI: 10.1021/jacs.6c02905 Journal information: Journal of the American Chemical Society Provided by National Institutes of Natural Sciences