Our group has pioneered an increasingly general synthesis platform for a range of functional molecules including molecular nanocarbons, π-conjugated organic materials, pharmaceuticals, and small molecules for plant biology and chronobiology. The uniqueness of our approach can be seen from the fact that most of the game-changing functional molecules that we have created were rapidly synthesized or discovered by our unique and powerful C-H activation catalysts and reactions.
Molecular Nanocarbon Science
Our representative achievement is the creation of a range of structurally uniform nanocarbons of fundamental and practical importance by bottom-up chemical synthesis. We have gained access to previously inaccessible nanocarbon materials with atom-by-atom precision. To this end, through the development of novel, highly selective molecule-assembling methods such as C-H activation, we have pioneered an increasingly general synthesis platform for molecular nanocarbons as well as biologically active compounds. Our work provides substantial progress in addressing the grand challenge of purity and uniformity in the field of nanocarbon science.
Nanocarbons – nanometer-sized carbon materials – conduct electricity, absorb and emit light, and exhibit interesting magnetic properties. Spherical fullerenes, cylindrical carbon nanotubes and sheet-like graphenes are representative forms of nanocarbons, whilst theoretical simulations have predicted a number of exotic three-dimensional nanocarbon structures that are yet to be synthesized. Obtaining structurally uniform nanocarbons –ideally as single molecules– is a great challenge in the field of nanocarbon science and organic synthesis in order to properly relate structure and function. Thus, the construction of structurally uniform nanocarbons is crucial for the development of functional materials in nanotechnology, electronics, optics, and biomedical applications. At present, however, synthetic routes to nanocarbons usually lead to mixtures of molecules with a range of different structures and properties, and they cannot be easily separated or refined into pure forms. The ‘mixture problem’ that arises during the synthesis of nanocarbons represents one of the most significant challenges in nanocarbon science and technology.
Through developing elegant new synthetic strategies and methods, we have created a number of structurally uniform nanocarbons and beautiful new forms of carbon. Noteworthy achievements include: (1) the development of single-step aromatic π-extension methods for the rapid and programmable synthesis of nanocarbon molecules (Nature Commun. 2015, Science 2018); (2) the synthesis of carbon nanorings, nanobelts and pure nanotubes (ACIE 2009, Nature Chem. 2013, Science 2017); (3) the synthesis of topologically unique nanocarbons such as warped nanographenes, carbon nanocages, all-benzene catenanes, and trefoil knots (Nature Chem. 2013, JACS 2014, Science 2019).
1. Single-step aromatic π-extension catalysts for the rapid and programmable synthesis of nanocarbon molecules
We have developed a number of unique catalysts for single-step aromatic π-extension and aromatic C-H activation that allows for the rapid synthesis of nanocarbon molecules in a programmable fashion (JACS 2011, ACIE 2015, ACIE 2017, Nature Commun. 2021). For example, we have introduced the concept of “annulative π-extension (APEX) chemistry”, which permits the facile synthesis of fused aromatic systems and molecular nanocarbons from simple aromatic compounds (Nature Commun. 2015, ACIE 2017). Our APEX reactions incorporate original catalytic systems, such as Pd(OAc)2/o-chloranil, to synthesize a range of molecular nanocarbons that are otherwise impossible to make. By using these original synthetic methods and catalytic systems, we have synthesized various molecular nanocarbons with atom-by-atom precision.
2. The synthesis of carbon nanorings, nanobelts and pure nanotubes
Currently, carbon nanotubes (CNTs) can only be produced as mixtures with regard to diameter and sidewall structure. Given that the electronic properties of CNTs are primarily determined by the sidewall structures, structural uniformity is critically important for CNT-based electronics. Thus, the selective and predictable synthesis of structurally uniform CNTs and ultra-short carbon nanotubes (carbon nanorings and nanobelts) is recognized as one of the greatest challenges in science and technology (Nature Rev. Mater. 2016). We have made significant progress toward this Holy Grail. We envisioned that the synthesis of structurally uniform CNTs could be achieved by a controlled growth process from a short carbon nanoring or carbon nanobelt (ACIE 2009). However, these highly strained rings and belts are described as “hypothetical molecules” or “dream molecules” in textbooks, and their synthesis was hidden for a long time.
In 2009, we achieved the first selective synthesis of carbon nanorings (cycloparaphenylenes), representing the shortest sidewall segments of armchair CNTs (ACIE 2009). In 2013, we succeeded in the first diameter-selective synthesis of CNTs using nanorings as templates (Nature Chem. 2013). The diameter of the nanoring template, which can be controlled using our method, determines the diameter of the final CNT. A range of carbon nanorings of varying sizes is also commercially available, thus encouraging others to explore the bottom-up synthesis of CNTs. Recent progress has shown the application of nanorings in a range of industrial applications such as true-blue light-emitting diodes.
Recently, we have succeeded in the first-ever measurements of the mechanical strengths of structure-defined, individual single-walled CNTs (Nature Commun. 2019). CNTs are predicted to serve as ultra-strong building materials for the construction of dream-like architectures, including a space elevator. Our discovery provides the first evidence on which CNT is most favorable in the pursuit of this fantastic goal.
In 2017, we achieved the first synthesis of a carbon nanobelt – a long-sought-after ultra-short CNT (Science 2017, JACS 2018). The synthesis of these highly strained, belt-shaped aromatic compounds had been one of the most difficult problems in chemistry for the last 60 years (even before the discovery of CNTs). This achievement is both an experimental tour de force and a triumph of synthetic chemistry. Our carbon nanobelt, which can be synthesized from p-xylene (petroleum feedstock), was commercialized in 2018, thereby accelerating the discovery of extraordinary properties, functions, and applications.
3. The synthesis of topologically unique, three-dimensional nanocarbons
We have also created completely novel, topologically unique nanocarbons (Acc. Chem. Res. 2019). Aside from theoretical studies that predict interesting properties for these types of species, three-dimensionally curved nanocarbons are a virtually unexplored group of materials. In 2013, we accomplished the synthesis of a novel warped nanographene (WNG) containing both positive and negative curvatures on its π-surface (Nature Chem. 2013). WNG is unique and clearly distinct from any other existing nanocarbon. The negatively curved geometry of WNG engenders a flexible configuration in solution, thereby displaying significant solubility. As WNG is also commercially available, many industries are now using WNG as a key molecule in optoelectronic devices. We have also synthesized a water-soluble WNG that exhibits green-yellow fluorescence with a long lifetime, good photostability and notably low cytotoxicity to cells (ACIE 2018). Furthermore, the water-soluble WNG was readily introduced into HeLa cells and induced cell death upon light irradiation, demonstrating the applicability for photodynamic therapy (ACIE 2018). More recently, we discovered that warped nanographenes self-assemble in a one-dimensional fashion to form the first all-carbon organogel (JACS 2021).
We designed and synthesized all-benzene carbon nanocages as a new family of molecular nanocarbons (Chem. Sci. 2013, JACS 2014). Carbon nanocages are 3D cage-shaped conjugated hydrocarbons consisting solely of sp2-carbons. We also synthesized a range of highly curved multiple helicenes (JACS 2015, JACS 2016, ACIE 2018). These include quadruple helicene featuring the most twisted benzene ring (35.3°) that has ever been synthesized. These novel nonplanar aromatics exhibit extremely interesting shape-dependent properties and have been applied in organic electronic devices.
Mechanically interlocked molecules such as catenane, rotaxane, and molecular knots have been of great interest owing to their attractive structures and their potential application in molecular machines. We have succeeded in the first synthesis of catenanes and a molecular trefoil knot consisting solely of para-connected benzene rings (Science 2019). Characteristic fluorescence of a heterocatenane associated with fast energy transfer between two rings was observed, and the topological chirality of the all-benzene knot was confirmed by enantiomer separation and circular dichroism spectroscopy. The seemingly rigid all-benzene knot has rapid vortex-like motion in solution even at –95 °C, resulting in averaged nuclear magnetic resonance signals for all hydrogen atoms. This interesting dynamic behavior of the knot was theoretically predicted and could stimulate deeper understanding and applications of these previously untapped classes of topological molecular nanocarbons. Undoubtedly, these topologically unique molecular nanocarbons will open a new field of science and technology. It should be noted that our all-benzene catenanes and trefoil knot have been selected as ‘Molecules of the Year 2019’ in C&EN of the American Chemical Society.
More recently, we have accomplished the synthesis of an infinity-shaped polyarene, infinitene (cyclo[c.c.c.c.c.c.e.e.e.e.e.e]dodecakisbenzene), comprising consecutively fused 12-benzene rings forming an enclosed loop (JACS 2022). We have studied its fundamental properties experimentally as well as computationally. These results open a new chapter in the chemistry of fully-fused, looped polyarenes. The established successful synthetic strategy would be an incentive to envision and create new amazing forms of nanocarbons whose architectures are limited only by our imagination. Notably, infinitene has been selected as ‘Molecules of the Year 2021’ in C&EN of the American Chemical Society.
C-H Activation/Coupling for Ideal Chemical Synthesis
The activation and transformation of ubiquitous but inert carbon-hydrogen (C-H) bonds in organic molecules not only represents an important and long-standing goal in chemistry but also has far-reaching practical implications. The Itami group has developed a number of unique and efficient catalysts for C-H activation/coupling making biaryls and heterobiaryls from unfunctionalized aromatic molecules. We have also developed a catalyst toolbox that can directly arylate almost all types of C-H bonds in heterocycles by catalyst control. Based on these catalysts, we successfully established general synthetic schemes for accessing privileged multiply arylated thiophenes, pyrroles, thiazoles, benzenes, and pyridines in a programmable manner.
These direct activation-transformation methods not only contribute to the realization of greener chemistry but also unlock opportunities for markedly different strategies in synthesis and accelerates discovery of a range of functional molecules (which we actually demonstrated by ourselves). So far, eight catalysts, ligands, and reagents for rapid chemical synthesis have become commercially available.
Synthesis of Bio-functional Molecules
The C-H coupling technologies and catalysts developed in the Itami lab allow the rapid synthesis of a number of biologically active compounds and pharmaceutically relevant molecules. In particular, some of the most recent results from the Itami group on the discovery of novel potent inhibitors of important enzymes make it clear that a truly efficient catalyst can have a huge impact in biology. Currently, a number of pharmaceutical and agricultural companies as well as chemical industries have already started to use our catalysts on a daily basis.
In the Institute of Transformative Bio-Molecules (ITbM), we are applying our catalysts and reactions to synthesize/develop key molecules that precisely control or visualize biological systems. Our representative targets include (i) molecules that control plant growth, (ii) molecules that modulate biological clocks of animals and plants, and (iii) molecules that realize innovative bio-imaging.