Discovery of 3D self-sorting ring nanostructures of three dimensional pillar[n]arenes
Research based on fusing expertise in synthesis of macrocyclic materials with frequency modulation atomic force microscopy technology yields results that offer the possibility of new biochemical nanoprobes to detect cancer cells
Interdisciplinary research is at the heart of the WPI Nano Life Science Institute (NanoLSI) at Kanazawa University. The importance of this approach is exemplified by the recent report by Tomoki Ogoshi and Hitoshi Asakawa of self-sorting pentagonal and hexagonal organic molecules in Communications Chemistry—their findings are expected to enable the synthesis of 3D multilayered columnar nanocavities with applications that include probes for gaining insights into biological mechanisms governing cancer growth.
“I was taking part in a Japan Science and Technology Agency (JST) project with the aim of inserting molecules into nanoholes using frequency modulation atomic force microscopy (FM-AFM),” says Hitoshi Asakawa, an associate professor Nanomaterials Research Institute at Kanazawa University and researcher at the WPI NanoLSI, Kanazawa University. “It was at this time when I was looking for challenging material structures to study that I met Tomoki Ogoshi at a JST meeting and realized that his research on macrocyclic compounds pillar[n]arenes was exactly what I was looking for. So we decided to collaborate.”
The interdisciplinary collaboration between Ogoshi and Asakawa yielded the results published in the Communications Chemistry paper on self-sorting assemblies of pillar[n]arene structures . Pillar[n]arenes are benzene units connected by methylene linkage at para-positions that yield highly symmetrical pillar-shapes that were first synthesized by Ogoshi and colleagues in 2008 .
“The main discovery in this work is that we were able to produce 3D pillar[n]arene structures by a self-assembly process that we refer to as ‘self-sorting’ that is governed by the compatibility of the shapes of the surfaces of pillar[n]arenes,” explains Ogoshi, a professor at the Graduate School of Natural Science and Technology and a member of the Supramolecular Chemistry group of the WPI NanoLSI.
Pillar[n]arenes, collectively named pillararenes, are cyclic organic molecules consisting of n so-called hydroquinone units, which can be substituted. Hydroquinone, also known as quinol, has the chemical formula C6H4(OH)2. It consists of a benzene ring with two hydroxyl (OH) groups bound to it at opposite sides of the benzene hexagon. The first pillararene was synthesized in 2008 by Tomoki Ogoshi and colleagues . The name pillararene was chosen since the molecules are cylindrical (pillar-like) in shape and composed of aromatic moieties (arenes).
“During a Sakigake project, I relied on the charge properties of pillar[n]arene to construct columnar structures by stacking them in a plus, minus, plus, minus sequence,” says Ogoshi. “This time it is the physical shape that is responsible for the 3D stacking in a mixture of pentagonal and hexagonal molecular building blocks of pillar[n]arenes, with pentagons binding to pentagons and hexagons to hexagons, without any mixing. This discovery was unexpected—a case of serendipity.”
In their experiments on the synthesis of the materials, Ogoshi and colleagues adsorbed cationic pillararenes (P+) onto quartz substrates, followed by the growth of multilayers of P+/P–/P+/ and so on, by alternately immersing the quartz into anionic and cationic solutions of pillararene.
Angle dependent ultraviolet-visible absorption spectroscopy measurements were used to measure differences in the pentagonal and hexagonal monolayers of the pillar[n]arenes. The experiments showed optical anisotropy, implying that positively charged pentagonal and hexagonal pillar[n]arenes structures were perpendicular to the surface due to contact between of the positively charged (cationic) edges of the molecules with the substrate. “These experiments showed that pentagonal structures only assembled on pentagonal structures, and likewise hexagonal only on hexagonal,” says Ogoshi. “This is the self-sorting phenomenon that we discovered.”
“For direct analysis of the formation of the ring shaped self-sorting structures, we used atomic-resolution frequency modulation AFM (FM-AFM) developed by us at Kanazawa University,” says Asakawa. “FM-AFM imaging was critical for unprecedented insights into the physical mechanisms underlying the formation of these structures.”
Asakawa and colleagues carried out fast Fourier transform (FFT) of FM-AFM images for both types of structures. They found clear long range order patterns for the pentagonal structures. But surprisingly, hexagonal structures grown on mica for the FM-AFM experiments did not exhibit FFT patterns associated with long range order, indicating the absence of long range periodicity in the columns.
“The FFT for pentagonal structures showed clear pentagonal voids with long range order,” says, Ogoshi. “The hexagonal pillararenes showed short range order. These experimental results agree with Monte Carlo simulations that our colleagues have carried out for these structures.”
Plans include attaching functionalized pillar[n]arenes molecules to AFM tips to act as probes to detect molecules and ultimately cancer cells.
Pillararenes synthesized by Tomoki Ogoshi in 2008 .
Structures of pillar[n]arenes, n = 5 and 6. Left, blue: cationic (positively charged) variants; right, red: anionic (negatively charged) variants.
 Tomoki Ogoshi, Shu Takashima, Natsumi Inada, Hitoshi Asakawa, Takeshi Fukuma, Yoshiaki Shoji, Takashi Kajitani, Takanori Fukushima, Tomofumi Tada, Tomonori Dotera, Takahiro Kakuta & Tada-aki Yamagishi. Ring shape-dependent self-sorting of pillar[n]arenes assembled on a surface, Communications Chemistry 1, 92, 7 December 2018.
 Tomoki Ogoshi, Suguru Kanai, Shuhei Fujinami, Tadaaki Yamagishi, and Yoshiaki Nakamoto, “para-Bridged Symmetrical Pillararenes: Their Lewis Acid Catalyzed Synthesis and Host–Guest Property”, J. Am. Chem. Soc. 130, 5022–5023, (2008).
 Tomoki Ogoshi, Tadaaki Yamagishi, and Yoshiaki Nakamoto, “Pillar-Shaped Macrocyclic Hosts Pillar[n]arenes: New Key Players for Supramolecular Chemistry”, Chem. Rev. 116, 7937−8002 , (2016).
Self-sorting through molecular geometries