The Infinite Potential of Molecules
The concept of "chemical space" in chemoinformatics illustrates that the variations of molecules reach astronomical numbers. For example, even if we limit ourselves to the five elements commonly found in pharmaceuticals—carbon, hydrogen, nitrogen, oxygen, and sulfur—and restrict the molecular weight to 500 or less, the number of molecules filling that chemical space exceeds 10 to the 63rd power. Theoretically, the number of possible molecules is virtually infinite. On the other hand, even a slight change in molecular structure can result in completely different properties. "Understanding the relationship between molecular structure and properties, and freely manipulating the functions of compounds to create molecules that contribute to the advancement of science and society"—this is the characteristic and ultimate goal of the field of organic chemistry.
For example, we recently created a new catalyst from just four elements—carbon, hydrogen, nitrogen, and oxygen—that enables chemical reactions previously considered difficult. The key to this development was designing a molecular structure capable of absorbing light energy to drive chemical reactions. A molecule designed so that a nitrogen-containing aromatic ring and an amide are orthogonal to each other skillfully moves electrons within the molecule upon absorbing blue light, transforming into a highly reactive state called a diradical. By utilizing this reactivity, it becomes possible to convert carbon–hydrogen bonds in alkanes, which normally hardly react, into other bonds.
Investigating the properties of developed molecules in detail can lead to unexpected discoveries and new applications. In the carbon–hydrogen bond conversion reaction using the new catalyst mentioned above, experiments showed that reaction efficiency improved dramatically when fluoroalcohol was used as a solvent. To clarify the reason, we used theoretical calculations to examine the excited state in detail, which suggested that the catalyst molecules form aggregates through hydrogen bonding, significantly increasing the generation efficiency of the excited state known as the triplet state, which is the active species. In other words, we found that the molecules we developed exhibit high reactivity as a catalyst only when both hydrogen bonding and blue light are present. Applying this characteristic, we established a technology to selectively activate functional groups capable of donating hydrogen bonds, such as carboxyl groups. Currently, it has become possible to precisely modify the molecular structures of natural products with unique biological activities, leading to the discovery of innovative molecules that control biological phenomena.
History shows that the discovery of a single new molecule can trigger significant societal development. At the same time, the astronomical number of molecules indicated by chemoinformatics means that infinite possibilities are expanding in the world of chemistry. I want to continue enjoying the excitement with my lab members that a molecule drawn from our own ideas could be the catalyst for changing the world. I hope that all of you will also challenge yourselves in this "unexplored molecular world" and become members who carve out the future with new molecules.