22 Nobel Prize in Chemistry was awarded again to Carl Barry Sharples in recognition of his contribution to click chemistry. Sharples is a legendary organic chemist. On the one hand, he is one of the rare scientists who won the Nobel Prize in Chemistry twice; on the other hand, Sharples blinded himself in an experiment because he did not comply with experimental norms, and became a "classic" negative case in experimental safety lectures in major universities. For the legendary story of Sharplace, please check out my previous article. In this article, I will introduce you to some of what click chemistry is.
What is click chemistry? Click chemistry, also known as "link chemistry", is a strategy proposed by Sharples to synthesize natural drug molecules. Many drug molecules are composed of hundreds of atoms. In the past, in order to synthesize such drug molecules, it was usually necessary to start from a simple molecule and add atom to this initial molecule step by step, gradually making this simple molecule bigger. This process can be understood as: when building a building in , we need to build one brick and one brick from bottom to top. There are three problems with the method of synthesizing drugs: First, this method is very inefficient. Each addition of a brick to the building means a new chemical reaction, so the synthesis of a drug molecule usually takes forty or fifty steps. Second, this method will cause a lot of waste of raw materials. In chemical reactions, raw materials cannot be converted into products 100%. There will always be losses during the reaction. Even if only 2% of the raw materials are lost in each step, after 40 steps, more than half of the raw materials are lost. Third, this method often has the situation of "demolition of the east wall to repair the west wall". That is, when we splice new atoms onto drug molecules, some chemical reactions may destroy the existing atoms.
is different from building a building. The difficulty of building the first brick when building a building is similar to the difficulty of building the 100th brick. However, in chemical reactions, the more atoms the molecule, the greater the possibility of side reaction . Therefore, when the molecule becomes large, it is actually quite difficult to accurately add new atoms to the drug molecule without affecting other atoms.
Sharplas said, why do you have to build a building with bricks and bricks? We can actually build the house layer by layer like building blocks, and finally splice several floors of houses into a building like building blocks. This is the so-called "modular assembly" method. This method proposes: When we synthesize drug molecules, we can actually synthesize some modular molecules first, and then directly splice these module molecules into the drug molecules we need.
Of course, a core question here is how to connect between each floor. Sharples' approach is to design a common linking group between each module molecule. It can also be understood as designing a common "concrete" between each floor. This kind of "concrete" must meet multiple conditions - first, concrete can be universal in different types of floors; second, concrete must solidify quickly enough; finally, concrete cannot cause corrosion to the bricks on the floor.
Through this module linking idea, the difficulty of synthesis of drug molecules has dropped sharply. Drug molecules that originally required forty or fifty steps to synthesize can now be achieved in four or five steps within a few hours. This synthesis strategy has a profound impact on organic chemistry. It promotes the synthesis of a large number of new drug molecules and biological molecules. This Nobel Prize can be said to be well deserved!
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I am a young Tangtang, a doctoral researcher at Fudan. Follow me to learn more about new life knowledge, popular science knowledge and scientific information interpretation!
