 Welcome everybody. As you know, this is a seminar that is really dedicated to science, to the joy of science. The Presidential Lecture series has that really aim to really touch us in a way that maybe other dedicated seminars does not. It should touch us in a way that we will be more interested and then see a little bit beyond the science that we work with every day. As a chemist, which also our lecture today is a chemist, we can see this of course also as a seminar that will be catalyzing our intersection between disciplines. This is what actually all is this all about. It's about to really choose your way that you want to look at science and technology, of course, and then be inspired to really go beyond and explore the intersection in between the disciplines to really see how you can put even more value into your science and how you can actually also be inspired to solve larger complex questions that need more than one scientific approach. So really there's one more thing about this Presidential Lecture and that is also to inspire the ones that are not really scientists and to really kind of follow a lecture that we also get more interest in the science and spread that the importance of science in the society. I don't know if we have anybody in here that is not a scientist, but if so you're also mostly welcome and this Presidential Lecture we are so very happy today to have a very distinguished professor, Makoto Fujita, and we are from Tokyo University and to get a more precise presentation Paula, please take the scene. This is my honor to introduce Professor Fujita. Professor Fujita introduced the concept of meta-directed self-assembly to supramune konarkenski, creating building blocks from transition metal group and organic molecules that self-establish into largest table, cyclic and three-dimensional structure. He's a university distinguished professor at the School of Virginia at the University of Tokyo. He has received numerous awards and honors for his innovative research, including the 2018 World Prize in Chemistry and the 2019 Imperial Prize. He was named a clarivate citation laureate in 2020. Molecular self-assembly based on coordination chemistry has made an explosive impact in recent years. Today this lecture will explore this compelling field and highlight Fujita's research. Thank you. This is the first lecture of the Presidential Lecture speaker. I heard that it's after your comment that this is your first presidential lecture. Is that right? No? What is chemistry? I hope that my lecture will meet your standard for the presidential lecture. Is it time for your microphone? Microphone? Yes, it's time. Okay, go ahead and make a close-up. Ah, okay. Maybe it's better. Okay, so I will use this microphone. Now, I hope it's clear. I'm a bit scared. What will be the subject? If you are asked to answer, my lecture is X1 or 2. This might be a switch to my presentation. Okay, so my lecture is based on chemistry and the key word is self-assembly and the coordination chemistry. Self-assembly, similar word is self-organization. Anyway, we have already experienced the phenomena of self-organization. Even the relationship between people becomes more spontaneously organized and the flow of money can be also spontaneously stabilized. Even the structure of the cosmic will be spontaneously stabilized. The mechanism of self-assembly or the mechanism of self-organization works. And we are discussing only the self-assembly of the molecular world. The small molecules, the random molecules, will be spontaneously organized. And in our study, this phenomena is induced by the coordination on the metal-beam interaction. So in our self-assembly system, we are using transition metal by adding metal ions to the solution of very simple reaching organic components. And all the species try to find their right pathway, leading to the most stable structure. In this case, this spherical large framework is spontaneously or constable. From this animation, you can understand the power and the principle of self-assembly based on the conditions. We have been working on this project since the 1990s. This year, we found the formation of spontaneous formation of a pralium-combalant square mark by simply combining the 90 degree coordination stroke and the veneer flow form by collision. So we expected the formation of the square framework, but we didn't expect the quantitative formation. Because in the originalization, this way, this way, this way, coming back to the original place is not high probability. Normally, it is point of originality. But in one person, we were very happy if we could get this square framework. But, beyond surprising, beyond our expectation, we obtained this compound and quantitatively, we are very surprised. So normally, the formation of the psychic framework is not done in the easy tasks. So connecting the both ends of the regular spark is not an easy transformation in case. But we observed their constant evolution. And we wondered why. And we realized that there is a diversity of the metal-beginned interactions. Once the components give the rigmas, then they have opportunities to go back to the components. And all the components enjoyed some dynamic reverberation. And they became more stable structures. And finally, it reaches to this state. So, as a result of some dynamic reverberation, this framework is formed in a quantity. Such a phenomenon or such a concept did not exist. Only the result. And even back to the 80s, we can find some historical values in the research. Such as, so much catamene, the two-ring of the ring-ring molecules. He got no reference in 2006. And he had a complex, reported by Shumari again, a concept. However, these examples didn't show any particular functions. So, in our case, in our system, we created not only the framework, but also the charities. Which is an excellent platform for further developing new reactions, new phenomena, new properties. So, since then, we have been developing the chemistry of self-assembly of not only the framework, but also charities. Regarding the chemically defined charities, all the chemistry is ascribed to the discovery of communism. So, synthetic molecules bind the randomized chemical species at the beginning, just a metamide. And the synthetic people tried to synthesize synthetic charities, the artificial charities, to bind the molecules. Of course, the phenomenon is similar to the binding of substances by enzyme. But as long as the framework cavity is constructed by covalent synthesis, the common ordinary chemical synthesis, there are limitations in terms of charities and fractions. But the mechanism of self-assembly removed the limitation. We could easily construct a bunch of bigger charities. And we could easily extend this concept to the construction of three-dimensional cages. We and others have developed self-assembled cages and developed new phenomena inside the cage framework. In recent years, our cage framework is getting bigger and bigger. So, in my lectures, I tried to overview the concept of chemistry from the origins of the latest among these. So, first let me discuss on the chemistry of cages, a regular component. So, starting from their square, we have developed many, many three-dimensional coordination architectures with charities. And depending on the size and shape of the cabinets, we could enjoy many, many new cases, new reactions, new properties. And among them, this M6L4 cage has been showing the remarkable potential. So, thanks to the tiny nature of metal, palladium centers, the complex is highly water-soluble. But in water, it provides efficient hydrophobic pockets, like in enzyme. So, in water, enzyme can also provide highly efficient binding pockets. Then in the cavity, we could accommodate multiple number of molecules, two or more molecules. Then by making the aggregation of small molecules in the cabinets, we could design and develop new reactions, new properties, new functions. So, it has been more than a quarter century. But still, this M6L4 cage is one of the center-plated in our laboratory. So, we can easily recognize two different molecules in a pair-wise set of functions. So, this is a pretty important phenomenon of the evolution to define new chemical reactions. Because most of the chemical reactions are by-molecular events between two molecules. We can easily make the close contact, the approximation of two molecules. This is exactly the same as the enzyme history. We can accommodate even polygomers, peptide polygomers, or even nucleotides in a sequence-selective question. Also, the otherwise unstable species can be trapped, and unusual reactions could occur in the cavity. This is the result of the insertable reaction, the subar reaction of 4, 5 electrons, and 2, 4 plus 2 cyclic additions. Also, upon photo-irradiation, we observed the efficient 2 plus 2 photo-additions. Surprisingly, these stable aromatic compounds, which normally do not participate in the insertable reaction of 2 plus 2 photo-addition. These stable aromatic compounds could easily undergo underwent the insertable reaction. So, even the non-activated naphtha can be the subar reaction. Regarding the anthracene, normally the central benzene beam shows the highest reactivity. But in our case, the pre-organization, the reaction side could address only the terminal beam. We observed quite unusual results of the activity in these other reactions. Most of the reactions were pre-organization and the products were compounded by oxalic reserve of the occasions. When the reaction product was this strongly bound to the activities, then incoming subsurface will kick out their product. Now, we observed the efficient catalytic channel. Yes, again, like an enzyme, we can use the catalytic side for chemical transformations. So, in one words, in some ways, our catalytic has been showing the molecular confinement we are still developing. At the relatively early stage of our chemistry, back in the 90s, our chemistry was branched into several different directions. So, your confinement effect is one of the directions. So, and not reason, but the obvious. So, we could make new directions. This simply means that this field was totally quiet, totally quiet. And that every day, with new discoveries. So, that's the reason why we could easily make very different directions in our studies. Let me just discuss the molecular entanglement. By, based on the coordination itself, we can easily construct highly entangled molecular structures. So, we have a simplest molecular entanglement. So, it's a formation of a two-ring of catamase. One ring is here, and another ring is here, so they are interlocking. So, at that time, back to the 90s or 80s, the catamase was used to be a very, very curious molecule. And it was almost their imaginary confluence of their old chains. So, at that time, two gynos, which are based on the phrasal. So, in the 80s, they created a very clever rational design and synthesis of catamase to bring catamase. Our catamase synthesis is almost ten years behind these early works. But the principle is totally different. Totally distinguished from these earlier examples. In that, two molecular rings slide into a catamase through a pathologically hidden mechanism. I mean that we can make their separated molecular rings by itself. And by changing the concentration, or by changing modulating, we are changing the polarity of the system. And the preform to molecular rings slide into a catamase. So, it's like a magic idea. Actually, the editor of Nature called it, named our complex molecular mass. And in the formation of this catamase, conceptually, this is the most important. This is the scientific sequence. In a metal-induced self-assembly, the topologically forbidden processes become allowed. So, for mathematicians, separate rings and catamase are not equivalent. They can never convert from here to here. But such a topologically forbidden process becomes allowed. Thanks to the invisibility of the metal-induced interaction. The driving force is the hydrophobic interaction in water. Then the two regular rings recognize each other. They discover each other. Then, very surprisingly, everybody believes that catamase is a very difficult target to synthesize. But our results demonstrated that the catamase is more stable than the separated rings. Nobody noticed that because there was no pathway. This process is topologically forbidden. But by removing this topological restriction, we could easily make a more stable catamase. And based on this concept, we have constructed many, many interlocking structures. Some of them were synthesized by design. And some of them were obtained just by chance, by action. So, even a three-dimensional structure can be interlocked by this based on this principle. Let me show you the one interesting example. So, this pyramid case is the component of the three-dimensional interlocking molecule. So, here you can see two planar reunions appeared with three linear molecules. Now, you can find the front planar chains to which we can insert planar molecules. And by extending the length of the pyramids, we can insert one, two, three cartilage molecules. So, by inserting the functional unit into the cavities, we could enjoy the plug-in functionalization of the kidneys. And when the starting number is more than six, then we used the technique of three-dimensional interlocking. Here, you can see the one pillar case. So, two planar reunions are pillar with three pillar molecules. Then, another copy of itself is interlocking in this way. Still, there are three compartments where planar molecules can be inserted, forming the stable, ready-stable, striking old, discrete, seven-parametric systems in the acceptor donor acceptor zone. What we did was just mixing all the components. So, six pillars, and four triangular reunions, three decimal molecules, and 12 metal hinges, metal condition. Just mixing everything, not everything. So, in principle, we didn't think of many, many, many, almost infinite number of products. However, only this structure is wrong, because this is the most stable. So, again, you can confirm, you can understand the problem, and the principle of self-sufficiency. Recently, we are playing with peptide, metal peptide framework is constructed, and we again observed the breaker in time. So, one of my colleagues, Tomo Tomo, who is now independent PA at the Tokyo Institute of Technology, he used to be a system professor at my group, he started the self-assembly using the peptide short fragments. So, long peptides will show the folding properties into alpha helix or beta-short. However, their short fragments cannot. So, it just shows the random combinations. So, the idea is, if their short fragment is linked to their reunions by metal coordination, then the metal peptide reunions would show their folding mechanisms. Then the assembly will help their folding process. And by folding the peptide framework, then the component becomes rigid. This is favorable for self-assembly. So, folding will help the assembly. Namely, the two processes help each other. We expect. Then we just mixed these very simple tri-cryptide ligands with two pyrrheum-condition side at the boson and a complex with metal elements. Then we observed very exciting structures which are beyond our expectation. We obtained w-helical, w-helical folding structures, and it's circular. In this case, you can see seven-classing to the original portion. And we can see many hydrogen folding between the two sides. They are folding. And assembled into the torus structure with seven-classing or eight-classing structures. And by increasing the strict demand of the AR group, we could easily expand their characteristics. This is nine-classing torus structure. And even ten-classing torus structure could be obtained. We confirmed the whole measurement structure in solution. So, when it's crystallized, when it's crystallized into the solid state, then there are some distortions. Because of the distortion in the ring, it was opened to become the toroidal w-helical complex. Anyway, we could easily construct the torus, not the torus ring frame, with n-classing torus pieces. The simplest torus structure is a tri-cryptide node with three-classing points, which was first synthesized by Jean-Fierce Poirier in 1988. And since then, the synthetic people tried to expand their structure. But as long as their framework is constructed only by covalent bonds, then roughly five or six-classing structures are almost a limitation. But we could easily remove the limitation. Then, by using the assembly, we succeeded the formation of seven-to-ten-classing torus structures. So, here are the lessons. Again, the forbidden ring-collecting process becomes allowed by metal industry assembly. Also, hidden n-tangling nature. So, fifth-time torus. We know the alpha-hex, beta-6 structures are very relevant, familiar with it. But we believe that n-tanglement is hidden-folding nature, which could not be expressed in nature, in proteins, because of topological restrictions. By removing the topological restriction, we could see, we could observe such a hidden-folding nature, so n-tangling nature of shock building by metal industry. Okay, so let me discuss the extension of the discrete framework into the infinite framework. So, you can understand by simply removing the checking group on the metal centers, that this square framework will be extended infinitely into the deep-sheep structures. And, in fact, in 2019-1994, we reported the same thing of extended coordination network squarely. At that time, the chemistry of metal over the creeper did not exist. Such term did not exist. Only Richard Robson was a pioneer in the chemistry of extended coordination network. And particularly in their publication in 1980, they clearly proposed the post-Zeroite porous harmony. So, we are also expecting the porous nature of the chemistry. So, maybe you compare these two substances. So, this is a discrete, this is an infinite material. The two chemistry are totally different. The solution chemistry and the solid state chemistry. And we noticed that the nature of the chemistry should be the same. So, our original idea was to translate the solution chemistry to be this science of solid state chemistry through the chemistry. The solution chemistry and the solid state chemistry will be equivalent through the chemistry. This is our original idea of why we started the extension of the square frame into the Grif shield structure. And since our first report, our group published a couple of papers on the metal in an extended network, structure itself. And after several years, several years later, in 2002, we had an important discovery. Single-grif sound, single-grif sound, guest exchange in the form of the porous coordination network. In the case, the monolithic molecules, typically the solvent molecules, they are mobilized at room temperature. They can behave like they do. And if the crystal is dipped in another solvent, then the porous solvent, the solvent is a porous when we completely repressed. And this guest exchange occurred in the single-crystal to single-crystal machine. So, namely, even after the solvent exchange, we could perform the X-ray crystallographic analysis. And by simply cooling the temperature, cooling the lower in the temperature, then the mobile molecules will be squeezed in a package. Well, then the solvent molecules are observed because of this porous membrane by the X-ray. So, even after the guest exchange, we could observe their exchanged new guest molecules. Then we immediately applied this phenomenon for the crystallographic observation of chemical reactions. So, namely, first, the solvent is absorbed into the package. Then the reagent will be absorbed into the package. Then the reaction starts, the reaction will occur in the package. And by carefully controlling the temperatures, we can freeze the reaction at any moment, at any stage. Similarly, in some cases, in the most successful case, we could see the pre-organization of the substance, and then the reaction intermediate in the case. And final product. Nobody, we can monitor the chemical reactions, the chemical reactions by NMR or by other spectroscopic methods. But we could observe the chemical reaction. We could monitor the chemical reactions, not by spectroscopy, but by X-ray crystal. We could visualize their solution techniques. And then we have published a couple of papers on the X-ray snapshot observation of shield solution state reaction. Then finally, we realized that we are developing the analytical chemistry. So we are thinking of the new materials, new functions, new functions. We are developing the chemistry from the viewpoint of material science. But finally, we realized we are developing the new analytical chemistry. If unknown compound, a structurally unknown compound is absorbed into the crystal, then after their absorption, we can see the molecule. We can determine the regular structure of unknown compound. Then we, 2013, we reported the Chris Hains-Moji method, which is a new X-ray technique that does not require the crystallization of the target molecules. So here is our porous complex. And here is a lead sample, or just a sample solution. You want to see the chemical structure of this unknown compound. And by treating the sample with our crystallization sponge, then our porous complex absorbs, absorbed their best molecule, target compound from the solution. And by picking up this best absorbed crystal and subjecting it to their cone X-ray crystallographic matrix, then we can see the molecule. So in addition to the original host framework, just absorbed, just penetrated, just molecules can be clearly observed. This is a fine example of our Chris Hains-Moji method. That does not require the crystallization of the sample. So you don't need to suffer from the crystallization. You don't need to suffer from the nightmare of crystallization. So that's probably the solution. You can easily get the crystals. The principle of the method is very simple. So to absorb the X-ray scattering, we absorb the, we need the pyramid carrier, the product array of the target compound, analyte compound. And everybody believed that crystallization is only the way to make your ideal vector array. It's not true. If the cavities are already, then if the cavities are already crystallized, then by calling the sample into the crystallized cavities, then we can make the order. This is the principle of our Chris Hains-Moji method. Did all the molecules create the same reactions? So there are many different directions. Ah, there are molecules. I will discuss in the next slide. Then, this is the most important Chris Hains-Moji that assembles the triaging chord trident ligand and the zinc chord. The cavity size is not too large and not too small to accommodate the ordinary organic molecules. And because they are inter-penetrating inter-digital structures, this is very important because in the state, the framework is very free. Namely, when the big molecule is coming, then the cavity can be expanded. With small molecules, the cavity can shrink. And the electron deficient aromatic rings are very friendly, very sticky to common organic molecules. And the hydrogen-alumatic sheath cone of the electron deficient Beijing rings in the sweet state works very efficient hydrogen bonding products. Namely, there are many, many binding sizes. Hydrogen bonding donor and hydrogen bonding acceptors in crystal. Now, the molecular recognition is very important. But when the gas is swinging into the pores, the gas molecules try to find their most colorful rays. At the same time, the host molecule, host framework is oriented to capture your gas molecule at the best position. Namely, there again, like in enzyme, so induced molecular recognition works. And after the gas absorption, we always observe their multiple weak interactions. So, if the cavity is very rigid and there are no binding sizes, the gas absorption could occur, but these molecules cannot be oriented. But the induced molecular recognition works. So, then molecules are not dissolved. They are oriented. Then, we can observe this molecule. And also, there is an answer very important advantage of our method. So, we can do the X-ray crystallographic analysis with only one tiny crystal of the crystalline form. Only one tiny crystal is ignored. So, and actually, we did the analysis of the submicrogram quantity of target camera. One crystal is placed at the bottom of the micro tube, which is dipped in a gas solution containing only the submicrogram quantity of samples. But still, our crystalline sponge absorbs the gas molecule from the solution. So, we could see the gas structure from only 500 nanograms, the submicrogram quantity of samples. We could clearly see the absorbed gas structure. We can dramatically scale down the crystallographic experiment in fraction experiment. And after obtaining this structure, we calculated the volume of the small volumes. And we realized that 500 nanograms is too much. So, we asked the students to try smaller scale. Then he called the structure and tried smaller scale. And we repeated this conversation. And yes, my colleagues easily analyzed the same compound from 150 nanograms. Still, we could get a very good extent. And also technically different, he also tried only the 10 micron meter size crystal for the crystalline sponge result. Then he called the record. Our record is only 5 nanograms. Not even from only 5 nanograms. We could clearly see the absorbed gas structure. So, probably nobody thought of such a trace amount extremely sober. Nobody believed that extremely sober is such a highly sensitive method. And the method can analyze such a very, very trace amount of particles. Why? Because we need more samples to make single crystal. So, from only the nanogram constituted samples, it's extremely hard to make single crystal. So, then we need a substantial amount of the samples. But by removing the crystallization state, then the X-ray crystallography is almost new analytical method that does not require crystallization and does not require the large amount of samples. Well, it's almost a new analysis method. Then now, we had an idea to combine the X-ray crystallography with reproductive gas chromatography crystallization, or even analytical HPH separation. So, here there are department oil components all separated by reproductive gas chromatography. All the compounds are liquid and volatile. So, it will disappear. However, we could analyze all the components by X-ray crystallography. Our perfume companies were very surprised when they bought a new X-ray machine. And we worked with beer companies, Japanese beer, and they analyzed, they succeeded in analyzing around 20 beta taste components involved in the house. So, studies have never been examined by beer companies. So, now we know the major components of the beta taste of beer. So, if by checking just the profile of the beer taste, we can blend the taste of your favorite beers. We can start a beer company. And by X-ray crystallography, we can determine the absolute configuration for right-handed or left-handed we can distinguish by X-ray. By observing the anomalous scattering derived from heavy atoms. So, namely, nobody, we needed to incorporate heavy atoms by chemical modifications. Then, we decided it's not an easy procedure. However, please remember that heavy atoms are already installed. Heavy atoms are already involved in the host frame. Because of the metal load, we employed zinc iodine. And by observing the anomalous scattering from the heavy atoms involved in the host frame work, then we could easily determine the right-handed or left-handed. So, and this is a very good news to synthetic people who are doing asymmetric synthesis studies. And they sent us many, many curious chiral molecules. This molecule has the actual chirality. Now, this is a planar chirality, a LAN chirality. They have a quarterly carbon centers, chiral centers. So, all of them there are no empirical rules for determining the absolute configuration of these chiral molecules. Then, we are and are determined. We are very happy to publish many collaboration papers with synthetic. I believe that this is the most reliable and the easiest method for determining the absolute configuration of chiral molecule. And we received many, many unknown natural products from natural products. So, there are two talented post-docs and so, they received many unknown natural products from natural product communities. And only in one or two years they analyzed over 70 natural products. And they analyzed over 70 natural products. So, our group was showing the highest performance in terms of the structure determination of natural products, including the absolute chiral chemistry. We could easily determine the 3D structure of the natural products. And according to our experience roughly 5% of NMR structures are wrong. So, we found the misassignment of chiral chemistry in their NMR spectroscopic structure It doesn't mean the 5% of natural product chemists are ready for it. It simply means that this is a limitation. This is a limitation. Probability is almost a limitation of the spectroscopic registration of 3D structure of complex models. We hope that in the future the spectroscopic study and the pre-science content their combination of these two will be a standard of determining the structure, 3D structure of ready complex natural products. So, currently we are further reducing their size of the sponge, Gryson's sponge. So, we are now using the new technique at the synchrotonal facility and we are also dealing using micro electron diffraction and the Gryson's size can be 10 microns. Then, with this size of Gryson's sponge in theory, we can analyze even a faint picogram of quantities. So, you might wonder if there is such a very good place and important content. Yes, yes. Just think of their type analysis. In a medical research, then so, you can detect by mass spectrometer of just a peak. So, it's just a faint of the picogram quantity. Now, you can just check by mass spectrometer of these and you can see this is a known compound for alcohol. But if it's not unknown compound now, you have no way to go further. So, if you get a very important compound from their patient or their cancer example, you cannot scale up their experiments. You cannot scale up. So, we are now collaborating with medical people to analyze their very key meta-varied analysis. Meta-varied analysis. They are single-tonal activity. So, the micrometer size crystal can be scooped with a micro-sized loop. We cannot see the crystal anywhere. But in the first section again, we can specify the positions. And in the second screening we get the diffraction data from many, many crystals. And all the data are merged. We are very surprised because we could get much, much better quality experiment. The soaking time absorption time is becomes very, very short because it's small. And the crystal can be easy. We can get the homogeneous guest-absorbed crystal in any way. So, we can get very good methods for analyzing. Even though they have to pick up the scale some. Let's see. Yes. This axis means the amount of the analyzed gamma. The structure information. The most sensitive device, most sensitive device we know is just a dog's sense. So, they can sense. But they give us just useful know-on. So, with mass spectrometer, we can get the monitor. And by NMR. So, we can get the even absolute configuration. But we need milligram quantity of samples to make single crystal. In this region, there are no approaches, no methods to approach to others. In this region, we have to give up. Now, for this region, our crystalline sports method just sending the scope. And now, we are trying this large amount in this. So, not only in chemistry, but also in biology and medical research, the sports method has been showing the performance. And not only in academic research, but also in industry of research and news, this thing. We believe that the sports method can change the game as long as molecules are conserved. Okay, let me also discuss simply a very big question. This is very simple. We are just actually big and big and big. Number is the larger in 2004, we reported the cell percentage of M12L24 models which are displayed by their animation which shape is roughly spherical, but it has the symmetry of cube of heat with 12 parts. Cube of the hidden has one of the asserting alchemy cells which are semi-dimensional complex for hidden, for hidden, and also two or more types of regular problems. Triangles, Korean war, triangle is dependable right? And now, who of them is the central balance structure in which four edges meet can be known? We are using a square planar transition method. So, the central balance transition method. So, in principle, we can target these four problems. So, the final structure drives to the crystal sphere to minimize the surface energy. We target four alchemy cells, and also one trying a tetravalent catalytic cell or regular problems or, in this case, octane. So, finally we could figure out five possible cells. Only five. Namely, in the square percentage of there are magic numbers. And the only five in values are a lot for their cells. So, we realize that there is a mathematical constraint modified that we ambition to synthesize all of them. And, in fact, in 2010, we got 2440, long period of healing. And then, in 2016, we got 3060 Aikoshito Decay. Let me give you an example. By showing the X-ray is a analysis structure. This is a structure of 24L48 long period of healing. So, you can count 24 metacenters 48 bridging units. Although I have never completed that. And then this is the crystal structure of 3060 Aikoshito Decay. And the size is comparable to the small to medium size proteins. So, our assembly goes to the protein side. This is molecular weight which is over 37,000. This is chemical formula. Chemical formula. But still, this is not a formula. So, formula has the distribution in the size and the formula and the molecular weight. So, distribution of the structure this whole structure means dispersed properties. We are aiming at the non-dispersed properties. Non-dispersed structures. So, we are very close to the nature structures. And the most important parameter that controls the final structure is the vent angle of the bridging ligand. So, this angle. From smaller vent angle to the final structure practically small. From the larger angles then the final structure will pick up. So, we know the result from the results. So, we wonder what happens in between. Which is as far as similar new begins who spent our divide these two angles with almost the same interval. So, we expected the formation of a mixture or just a new structure at the expense of the cement. Very surprising, the result was very impressive. We observed the critical change in the structure. Namely, we observed the sharp threshold existing of 131 elements. We didn't see the formation of a mixture. Always small or large. Again, we wonder why. And we realized that even the initial difference is very small. Such a small difference will be amplified during the assembly from many many components. Many many species. So, thanks to this amplification effect if the given conditions slightly prefer the smaller structures and then everybody come to small structure to the small structure or as possible. In other words, we are unable to make a mixture in the server center. Back to this roadmap. This axis is at the server assembly parameter. And then we can make the analog change in the server assembly parameter. There is no restriction in the values. But the output is digital. So, only five structures are allowed. And this analog digital relationship is particularly important to control the structure. To make the structure very stable. I mean that at a certain range at a certain range of server assembly parameters we can always reach to only one structure. Because there are no other possibilities. And once this roadmap is formed it's very stable at a certain range of external stimuli. Well, productivity is the most important issue in chemistry. We normally control the productivity by static effects or by electronic. However, the selective formation of this giant framework is controlled by mathematical restriction. We can say that this is the mathematical control of the structure and actually the same principle is employed in the formation of large-scale virus capture structures. So, they have the microstatic cathedral in all the COVID virus. I ask the schematic. So, because they are using the mathematical restrictions to control the structure of the virus capture. So, the nature is the great mass emotion from the original theory. What happens if we make the much further larger, slightly larger? But different time, the core ring was replaced with a cylinder. The difference is only very small, but such a difference, small difference, we will remember. Actually, we obtained a huge structure but the NMR spectrum was really low and the mass spectrometry didn't show any regularity. So, then we tried the acquisition, and finally we could see. Then by observing the actually preliminary we are really surprised. So, we had a totally unexpected situation. And what we observed was the unexpected L60 structure appeared. But this is the electron density observed at the early stage of the crystallographic process. You can see it's roughly spherical and you can also see square and triangle, square and triangle. It's highly similar but this simple framework topology, network topology does not belong to the Archimelian service. And more surprisingly we could not find this geometry in any text of geometry. So, what is this? We are very surprised and very frustrated. We have a monarchy. We have substance. We have extreme structure but we cannot publish because we cannot explain. So, couple of months we are very much frustrated. Finally, one of my colleagues, Daishi Fujita another Fujita he is a smart guy. He established a new mathematical discussion that clearly explains their structure of unexpected polyhedron. So, we were inspired by the idea of a Goldberg polyhedron which is a complex polyhedron made from hexagons and pentagons. From only hexagons we always get the infinite high-hemp ship we can never close. But by incorporating pentagons we can make the convex surface. And pentagons and pentagons by including 12 pentagons we can finally close their structure. Depending on the relative position of two adjacent pentagons we can define many of the sheets of different Goldberg polyhedron. So, in this case this Goldberg polyhedron can be expressed as the Goldberg 3-2 case of this and can be used. This is Goldberg 3-2 polyhedron. So, each can be defined by the relative position of adjacent pentagons with two indexes HMK. So, the fillet is one of the Goldberg polyhedron. So, from pentagons to pentagons you can move one stick and one stick. So, this is Goldberg 1-1 and the polyhedron. And despite the sketch it has the Goldberg 1-2 projects. So, and the all the Goldberg polyhedron are the trivalent structure in which three edges meet at every point. In our new discussion we simply extended the Goldberg polyhedron from trivalent to the tetravalent of the projects in which four edges meet at every point. Now, this is the discussion. Then, Goldberg invented their conventional genome to describe two indexes HMK with only one letter. So, the summation the square of the summation of these two vectors can be described as such. This is a high school mathematics basically. So, if you have the t number you can re-calculate the digit HMK. And maybe this is just one letter description of the two indexes. In our extended Goldberg polyhedron the basic meant work is a square bridge square square square. Again, we can never cross. Including a triangle that we can make convex surface. And then finally we can cross. Again, each extended Goldberg polyhedron can be defined by the derivative position of the two indexes. And by analogy we define a tumor by making the square of the two vectors. So, in this case we can adopt the Pythagoras equation. This is junior high school mathematics. And based on the Pythagoras equation we could generate a series of magic numbers or Q numbers from digit numbers each year. So, and each Q number represents one specific relationship of triangle and triangle index. For example, for Q number 2 H and K should be 1 and 1. The derivative position should be one step and one step. So, it describes the geometry of cube of the hill. The next possible Q number is 4. H and K should be 0 and 2. 0 step and 2 step. 0 step and 2 step. Representing the long cube of the hill. And the next possible Q number is 5. H and K should be 1 and 2. One step and 2 step. One step and 2 step. And this is the approach. This is agreement which we encounter in action. Now, everything is clear. Everything is clear. So, we can describe the new series of perihidra, which we termed the extended of perihidra. So, which are convex perihidra made from square and triangle. So, what we encounter was the Q number of 5 structures. When Q number is over 5 in these structures this is very important. So, the square window cannot be perfect plane. So, one corner of the square is slightly deviated from there part. Stretch this stretch this it doesn't need the definition of mathematical definition of perihidra because it's not surrounded by. I don't care such a small deviation. Then now we could find the new series of perihidra or we can say accepting the small deviation of one corner from the perfect square in the square. Square. Anyway, everything is clear. And we could easily repair this table. So, from Q numbers we can easily account your calculator, the number of vertices. And they are very surprising. We believe that we are synthesizing the series of Archimedes or Archimedes but it is not true what we have synthesized was a series of extended gold and gold. With a Q number of 1 to 5 without missing anybody. So, and they are everything is clear. But more importantly the discussion made us possible, made it possible to predict our future structures. So, namely from this table we realize that the next possible structure should be 48 and 54 and 60. So, our difference is very small so we believe that we can make M48. Then we became very serious synthesizing many new beginners and examined many different conditions for the assembled assembly. And finally we got our M48 L96 extended old bug for Hydra which was predicted by our own mathematical discussion. This is the first discussion. So it can be described as a tetra variant extended gold bug for Hydra 2 to 4 Hydra with the Hydra with Q number 47. We are within reach of the construction of the biological structures in nature. Let me quickly show the next couple of slides. So, again we have important lesson. Mathematical rationalization can predict future structures. This is a very important lesson from our study on the gold bug assembly on the gold bug for Hydra. Back to the metal peptide chemistry we incorporated plurin because plurin can form the term conformation. We expected a more entanglement of three-dimensionally entangled structures. And yes, we got 3D dimensionally interlocked very complex structure consisting of four independent metal peptide in-frame. So, how can we describe this project? We discussed with mathematicians and they explained that this project can be described as a tetrahedral four rings are placed on the four faces of a tetrahedral. And then you can make the double twisting each of the tetrahedral. Then you can get this approach. So tetrahedral is one of the platonic threads and the three of them have the trivalent structures. Again, we got the new road map. So three trivalent platonic threads structures could be possible in the cells. And in fact from this diagram, we got cubic ring. This is the complex structure. Again, you can see one metal peptide ring and six metal peptide rings interlocking with a cubic symmetry. And here it's a M60 M60 tetrahedral ring. So it's almost a crazy idea, a crazy target from scratch. So from scratch, nobody designed such a crazy target. But for us so it's mathematically predicted the difference is only one parameter. By modulating only one parameter we can reach here. So for us these two structures are almost equivalent. So finally we got this M60 or M60 structure. This is the moment champion structure in terms of the number of these. So currently we are capturing proteins and so we discuss detail protein chemistry in engineering. So the proteins protein aggregation is not allowed by the case. Now that makes proteins very very stable. So under forcing conditions the proteins can be once degraded. I hope that you do not hear HSQC. It's just a fingerprint of protein folding structure. It's once broken but when it's re-proffered to the original acres conditions then the original structure re-generate. So CLE is a protein particularly used. It was refolded in a case. Refolding a protein by casing is the important action of chaperony proteins. We could mimic a chaperony function in our cell percentage for our future vision here. Let me summarize my book here. This slide shows the scientific significance of our studies over the last three decades. In the tradition of this disease we like to create new shapes while in our new states. But in our study we created a new interdiscipline in which in our chemistry creates new shape of that it would be a new principle of creating chemical frameworks on the dimension of the brain. I cannot acknowledge all the people because I hope that in the past of research in a group here are the pictures of my former and current key globalists who used to be our staff or assistants or sociologists. No, this is the current group of us. Here are the key scientific staff young people.