On the evening of October 5, after the Nobel Prize in Chemistry was announced, Dong Jiajia planned to call her mentor Carl Barry Sharples, but it has not been connected for the time being.
But he knew that this "old man" in his 80s would not be too excited about Nobel Prize . After all, he has won too many awards; and this is his second time to have won the Nobel Prize in Chemistry.
"He told me when we communicated privately that the honor of is meaningless to him." said Dong Jiajia.
Dong Jiajia is now a researcher at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, and has been doing research with Professor Sharples for more than ten years.
In his heart, Sharples is the "perfect" scientist.
Click Chemistry: With a click, the
2022 Nobel Prize in Chemistry was awarded to American scientists Carolyn R. Bertozzi, Danish Scientist Morten P. Meldal, and American scientist K. Barry Sharpless for their contributions in the fields of click chemistry and bioorthogonal chemistry.
Image source: Nobel Prize official website
Around 2000, Sharples proposed a new field: click chemistry.
This is a simple and reliable chemical form that reacts quickly and avoids unnecessary by-products.
Cheng Liang, a researcher at the Institute of Chemistry, Chinese Academy of Sciences, explained that is commonly understood as two things that can be placed together and can be directly reflected, just like building blocks put together, and with a click, it will be done. Even if you are not a chemist, you can still perform chemical reactions after getting the substrate. The complexity of chemical synthesis is greatly reduced.
With click chemistry, researchers can also more accurately regulate some key chemistry steps. Not long after
, Meldar and Shaplers each independently proposed copper-catalyzed azide-alkyne cycloaddition. This reaction is described as elegant and efficient.
. In addition to being carried out in test tubes, it also needs to be broadened to cells and even living organisms. If this reaction interferes with other functional groups and components in the cell, it will affect the function of the cell. Cheng Liang said that the so-called "orthogonal" means that it does not interfere with the original biochemical reactions in the cell. Bioorthogonal reactions are to allow probe molecules and reporter functional groups to react quickly and efficiently without affecting the normal interaction between biomolecules.
"At present, most click chemistry is used in biological orthogonal reactions. Of course, click chemistry is widely used, and some physicists will use click chemistry to make functional material ." Cheng Liang said.
Click chemistry developed by Sharples is faster, but it requires copper ion . However, for organisms, copper ions are toxic. Bertosi proposed two copper-free click chemical reactions (bioorthogonal reactions), which are more suitable for life systems.
Lin Shixian, a researcher at the Institute of Life Sciences, Zhejiang University, described that it was equivalent to looking at the instructions in the past and building blocks in sequence; now, copper-free catalysis does not require instructions, and can be spliced relatively freely. Therefore, Bertosi's method allows click chemistry to enter the organisms, and biological orthogonal reactions are widely used in life science research. Cheng Liang believes that the future application scope of
can be expanded to two aspects: addition and subtraction. The former refers to allowing smaller precursors to react efficiently and create new molecules in situ at specific locations and specific times in the organism; the latter refers to allowing molecules with active ingredients to enter the organism and using bioorthogonal chemistry to release drug molecules that are active against target cells at specific locations at specific times and locations. "The hot topic of research is how to make addition and subtraction more accurate," said Cheng Liang.
click chemistry mainly involves the connection between different functional groups. Therefore, researchers are broadening the reaction types of click chemistry and adding available tools to allow the "click" connection between more functional groups.
Dong Jiajia told Science and Technology Daily reporters that, simply put, what everyone needs to do is to find unique and difficult-to-observe reactions and apply them.
"Captained" Sharples
Sharples won the Nobel Prize in Chemistry in 2001 for his contribution to chiral catalytic oxidation reaction.
Some scientific researchers admitted that the reason why they did not dare to predict Sharples' award before was because they felt that he had won it once after all.
Lin Shixian said bluntly that this is a milestone in the history of Nobel Prize . "In this era, winning two Nobel Prizes is a very amazing achievement!" The two awards from Sharples meant that he had made groundbreaking work in two completely different fields, "He was awarded the title of the Nobel Prize winner."
In 2001, Sharples won the Nobel Prize in Chemistry for chiral catalytic oxidation reaction. Image source: Nobel Prize official website
As early as 1970, Shaplers was injured in one eye due to a chemical experiment accident. Since then, he has basically worked with one-eyed eyes. After having won great honors, Sharples jumped out of the field he was familiar with and opened up a new research direction.
Dong Jiajia said that after proposing click chemistry, Sharples suffered a lot of criticism and criticism, including the famous synthetic chemist and his old friends. Sharples's wife told Dong Jia's family that there was a time when Sharples went out to give a report, and many people liked to see it. It’s not because they want to see what click chemistry is, but because they hear that Sharples went crazy and wanted to see how crazy he was.
But time says it all.
What kind of person do you think is your tutor? Hearing the reporter's question, Dong Jiajia blurted out - "Perfect scientist!" "He doesn't care about other things, and he does research completely driven by curiosity. There is only science in his eyes and heart. Pure, no utilitarianism." He doesn't know how much he has to pay, and forgetting to bring his passport to the airport often happens. The only thing Sharples has to worry about is science. Sharples is not in a hurry to post articles. He advocates making original discoveries, focusing and curious. However, Sharples will not take action, and once he takes action, he will be "earth-shaking".
In November 2008, Shaples gave a speech on scientific research and innovation thinking at Tianjin University . In March 2009, Dong Jiajia joined his research team, and the teacher gave him both the PPT and the original speech. "I have read this report hundreds of times." Dong Jiajia later translated the ppt and speech page by page and posted it on the WeChat official account of his research team. "What he has the greatest influence on me is to teach me how to research and how to be a human being."
Sharples described himself as an explorer. "If you want to discover new things, the first step in a journey is to learn to coexist with uncertainty and learn to accept failure as usual, because the risk of finding unknown things is as great as being a high acrobat who never tied a safety rope."
"When I was working on the lab bench, most of my reactions didn't work, but I never saw them as failures. I didn't work thoughts that would always bring me more ideas about the next step of trying. So, there is no concept of 'failure' in my dictionary," Sharples said.
There is a broad space for imagination in this field in the future
2022 Nobel Prize in Chemistry has been settled. Lin Shixian said that in fact, domestic work in this award field is also very cutting-edge, and it is on par with the international level. Some bioorthogonal reaction concepts and applications are at the leading international level.
There are also many scientists who have made outstanding contributions to click chemistry and bioorthogonal chemistry. "Maybe because of the restriction of three award quotas, some people did not win this award, and I feel a little regretful." Lin Shixian gave an example and said that Professor Chen Peng's team of , School of Chemistry and Molecular Engineering, Peking University, took the lead in proposing a bioorthogonal shearing reaction, breaking chemical bonds through bioorthogonal reactions to activate protein and release drugs. This is also a very well-known research in the field of bioorthogonal chemistry.
"Click chemistry and bioorthogonal chemistry is a new chemical reaction and chemistry theory proposed by chemical scientists who actively embrace life sciences and actively meet the challenges of life sciences.The theory building has just been built, and it can bring a very broad imagination space. "Lin Shixian believes that they can provide chemists with very unique technical means and a series of tools to accurately and specifically interfere with life systems. These studies are equivalent to providing molds and modules for building blocks. As for whether they will be used to build aircraft, aircraft carrier or spacecraft in the future, it is worth further exploration by scientific researchers.
Lin Shixian predicts that in the next 20 years, many researchers who use the basic concepts and ideas of chemistry to study the process of life sciences can win the Nobel Prize.
column editor: Zhao Hanlu Text editor: Yang Rong Title picture source: Visual China Picture editor: Cao Laiyuan
Source: Author: ◎ Science and Technology Daily reporter Zhang Gailun
