"I engage in chemistry research as I did when I was young. In order to excite, discover, and take risks, and to catch the most difficult fish in the unknown ocean."
——K. Professor Barry Sharpless
Yesterday, Professor Barry Sharpless K. Professor Barry Sharpless from the Scripps Institute in the United States, and Professor Morten Meldal from the University of Copenhagen, Denmark for his outstanding contributions in click chemistry research, and Carolyn R from Stanford University . Professor Bertozzi won the Nobel Prize in Chemistry together. Professor Sharpless won the Nobel Prize in Chemistry in 2001 for his outstanding contribution to asymmetric catalytic oxidation reactions. Now he won the award again 21 years later, which also made him the second scientist in the history of Nobel Prize to win the Nobel Prize twice. In today's article, the WuXi AppTec content team will come to the new Nobel Prize winner with everyone to understand his life and research.
▲This year's Nobel Prize winners Professor Carolyn R. Bertozzi (left), Professor Morten Meldal (middle), and Professor K. Barry Sharpless (right) (Photo source: Nobel Prize official website)
From fishing to chemistry
When he was a child, he spent most of his summer on the coast of New Jersey. His parents had a villa there, and the young Sharpless liked to work on a fishing boat at a relative's house and became a "child laborer" hired by his uncle. Most fishermen value the number and size of fish they catch, while Sharpless pays more attention to whether the fish they catch are rare. Nothing is more exciting than catching a mysterious creature from the water that you haven't seen before! Professor Sharpless recalled that his first lab was the Manasquan River in New Jersey, and then the Atlantic Ocean. His fishing experience also shaped his attitude towards chemistry research in the future, starting from curiosity and pursuing the most difficult goals.
▲The young Sharpless is keen on fishing (Picture source: Reference [6])
Sharpless showed his talent in chemistry when he was studying for his bachelor's degree at Dartmouth College (Dartmouth College 3). He is the first among 135 students in the organic chemistry course. At that time, the storage room of compounds could be said to be able to enter at will. For Sharpless, Periodic Table is like the ocean. "People like me, if they have the chance to enter the lab, will make us fall in love with this business completely." Sharpless recalls, "I can remember all the compounds in the pantry, their smell, their taste." His mentor, Professor Tom Spencer, admired his talent and suggested that he go to his tutor, Professor E. E. van Tamelen of Stanford University, after graduation. It was in Professor Tamelen's lab that Sharpless found the "first fish" he wanted to catch as a chemist.
Periodic table of elements is like an ocean, catalyst is the most difficult fish
At Stanford University, Sharpless developed a strong interest in discovering new chemical reactions. 's study of enzyme-catalyzed him with awe of the selectivity of biocatalysis. However, as a chemist, the difficulty of using enzymes to convert compounds also made him very depressed. In order to discover new chemical reactions that other chemists can use, he began to develop catalysts using simple metal composites.
At Stanford University, Sharpless also met his future wife, Ms. Jan Dueser (later Jan Sharpless). Sharpless said her support is one of the important reasons for her success, and Ms. Jan Dueser's origin of the name of the click-through chemical is also a contribution.
▲Sharpless couple (Picture source: Reference [4])
1969, Sharpless came to MIT (MIThings 3) to study for a postdoctoral degree, studied enzymatics, and later became an assistant professor at MIT. In the following time, he focused on developing methods for asymmetric epoxidation reactions that can produce compounds containing oxygen atoms with specific chirality. Although the chiral molecules of have exactly the same molecular formula, the three-dimensional structure is mirror symmetrical like our left hand and right hand, which is exactly the opposite of (see the figure below). Borrowing the concepts of left-hand and right-hand, scientists also use left-hand configuration and right-hand configuration to distinguish these two different structures.
Image source:!Original:UnknownVector: -- πϵρήλιο, Public domain, via Wikimedia Commons
In the chemical reaction to generate compounds, the catalyst has an important function. They can significantly increase the speed of chemical reactions. The most common catalyst in the human body is the protease , which exist in all organisms and drives the chemical reactions necessary for life. Many proteases are characterized by catalyzing the formation of compounds with one chiral configuration. Drawing on this "asymmetric catalysis" ability formed by nature, Professor Sharpless has also begun to find and design catalysts that can perform "asymmetric catalysis".
After years of hard work, his team discovered that using titanium compounds and chiral ligands can complete the "asymmetric catalysis" of the epoxidation reaction. To demonstrate the purpose of this reaction, his team synthesized a chiral pheromones that attract female gypsy moths. Their experiment was so successful that the lab team members attracted a large number of gypsy moths in the wild because of the compounds left on their clothes. The breakthrough contribution in this field also led to Professor Sharpless's Nobel Prize in Chemistry in 2001.
Click chemistry that simply connects molecular modules together
1990, Professor Sharpless came to the Scripps Institute. After his successful field of asymmetric catalysis, his research interests began to shift in other directions. One of the important ideas is that constructs molecular components like Lego building blocks , which contain molecular groups like seat belt buckles. As long as these two groups meet, they can "click" (click) like buckles to covalently connect the two molecules together.
▲Professor Barry Sharpless and Professor Morten Meldal laid the foundation for a new form of chemistry - click chemistry, which allows molecular modules to be put together quickly and efficiently. Professor Carolyn Bertozzi's work has advanced click chemistry to a completely new field and applied it to living organisms. Her bioorthogonal reactions can occur without interfering with the normal chemistry of cells (Image source: Reference [8])
2001 in the well-known journal Angewandte Chemie International In a paper published on Edition, Professor Sharpless and colleagues wrote: "Inspecting molecules in nature shows that nature prefers carbon-heteroatomic bonds compared to carbon-carbon bonds. Whether it is nucleic acids, proteins, or polysaccharides, they are spliced by small molecules through carbon-heteroatomic bonds, and the total number of these small molecules is only about 35. If humans can learn this set of rules, they can quickly and reliably synthesize a large number of useful molecules..."
In 2002, Professor Sharpless's team discovered that using the Cu(I) catalyst, the Huisgen cyclization reaction that previously needed to be carried out under high temperature conditions can be completed at room temperature and in aqueous solution. This reaction is simply called CuAAC.
▲As early as 2015, Professor Sharpless introduced at the WuXi AppTec academic seminar that click chemistry
has wide application value because it can reliably couple two molecules together in different systems.Biochemists can connect fluorescent molecules to proteins, and the design of antibody-conjugated drugs can use click chemistry to connect toxic drugs to specific positions of antibodies... At present, click reactions have been widely used in many fields such as drug research and development, functional material , supramolecular self-assembly, chemical biology , etc.
Simple and useful chemistry
In his speech when Professor Sharpless won the Nobel Prize in Chemistry for the first time, he mentioned that the compass that guided his chemical research direction, in addition to "catching the most difficult fish in the unknown ocean", there are also the pragmatic concepts instilled in family education . He said that in the field of chemistry, "elegance", "smart" and "innovation" are often positive words used to describe new chemical reactions, and in his mind, the most important word is "useful". From the perspective of chemical reactions, usefulness means a wide range of uses, easy to carry out, and an important transformation of easily available raw materials. Professor Sharpless uses asymmetric oxidation reactions and click chemistry to interpret the "compass" that guided his career in chemistry, and also brings chemical tools that benefit the world. The winning of the Nobel Prize in Chemistry twice is also the best compliment for his contribution to chemistry.
Reference:
[1] Searching for new reactivity. Retrieved October 5, 2022, from https://www.nobelprize.org/uploads/2018/06/sharpless-lecture.pdf
[2] From Curiosity to Click Chemistry: K. Barry Sharpless Forges His Own Way. Retrieved October 5, 2022, from https://www.scripps.edu/newsandviews/e_20111107/sharpless.html
[3] Three scientists win chemistry Nobel Prize for developing ‘click’ and ‘bioorthogonal’ chemistry. Retrieved October 5, 2022, from https://www.statnews.com/2022/10/05/nobel-prize-chemistry-2022/
[4] 2019 Priestley Medalist K. Barry Sharpless works magic in the world of molecules. Retrieved October 5, 2022, from https://cen.acs.org/people/awards/2019-Priestley-Medalist-K-Barry-Sharpless-works-magic-in-the-world-of-molecules/97/i13
[5] A cautionary tale from the past. Retrieved October 5, 2022, from https://news.mit.edu/1992/safety-0311
[6] K. Barry Sharpless Biographical. Retrieved October 5, 2022, from https://www.nobelprize.org/prizes/chemistry/2001/sharpless/biographical/
[7] Nobel Prize Laureate Professor Barry Sharpless Visits WuXi. Retrieved October 5, 2022, from https://wxpress.wuxiapptec.com/nobel-prize-laureate-professor-barry-sharpless-visits-wuxi/
[8] The Nobel Prize in Chemistry 2022, Retrieved October 5, 2022, from https://www.nobelprize.org/uploads/2022/10/press-chemistry2022.pdf
