Nobel Prize in Chemistry

11 Oct 2022 Nobel Prize in Chemistry

Source: The Hindu; The Indian Express

News: Chemists Carolyn R. Bertozzi and K. Barry Sharpless from the U.S.and Morten Meldal from Denmark received the Nobel Prize in chemistry for their research in click and bioorthogonal chemistry.

Complications in imitating naturally occurring compound  

• Replicating reactions that involve bonds between carbon atoms is expensive and often leads to side reactions and loss of material.So,the need arises to develop synthetic strategies like click chemistry to fulfill the same purpose.
• Simpler reactions may avoid the loss of material as well as the unwanted side reactions due to strong intrinsic drive for the molecules to bond together.
• Barry Sharpless invented the click chemistry where instead of making carbon atoms react with each other he utilizes the smaller molecules with complete carbon frame for reactions.
• According to The Nobel Foundation these smaller molecules can further be linked using oxygen or nitrogen atoms as bridges.

About Click Chemistry

• Click chemistry is a branch of science invented by Dr.K.Barry Sharpless to explore the assembly of molecules.
• Click chemistry is a functional field where molecules snap together quickly and efficiently like a click.
• In click chemistry, molecules that wouldn’t typically bind with one another are made to do so in an efficient and uncomplicated manner.
• According to Dr. Sharpless conditions for click chemistry reaction is that it should occur in the presence of oxygen and in water.
• Dr.K.Barry Sharpless defined click chemistry as a “set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links”. 
• Importance of click chemistry according to Dr. Sharpless: Even if click chemistry fails to perfectly imitate naturally occurring compounds, it can help find molecules that fulfill the same purpose.

Timeline of Click chemistry:

• Dr. Sharpless is the originator of the concept of ‘Click Chemistry’ as he was the first scientist to work on click chemistry.
• Immediately, Dr. Meldal and Dr. Sharpless independent of each other presented the improved form of the azide-alkyne Huisgen cycloaddition reaction i.e. copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction 
• Dr. Bertozzi developed click reactions that work inside living organisms by demonstrating that these bioorthogonal reactions do not disrupt the normal chemistry of the cell.

Research of Dr. Morten Meldal

• During one of her research to find potential pharmaceutical substances. Dr.Morten Meldal and his team tried to react alkyne with an acyl halide with copper ions and palladium as catalysts 
• Analysis of the reaction: Alkyne and the azide created a ring-shaped structure called triazole after reaction of  alkyne with the “wrong” end of the acyl halide molecule.
• Result of Dr. Meldal’s reaction: Catalyst copper ions controlled the reaction, and acyl halide mostly remained untouched.

                                                                                                                            CuAAC reaction

                                                                                              Image Credit: The Royal Swedish Academy Sciences

Contribution of Dr.K. Barry Sharpless

• In one of his research, Dr. Sharpless described the copper-catalysed reactions between azides and alkynes as an  “ideal” click chemistry reaction. As the reaction worked well in water, satisfying basic criterion for click chemistry.
• Sharpless won the Nobel Prize for the second time. His first Nobel Prize was for creating Lego blocks (creating molecular building blocks) that could snap together quickly and efficiently.

Dr. Carolyn R. Bertozzi’s addition to the research

• She began her research in the early 1990s, to understand functioning of the glycan. For this she started mapping a glycan that attracts immune cells to lymph nodes.
• She tried to map the glycans using the chemical handles if cells incorporate the modified sialic acid in different glycans.So in order to do that she explores the possibility of production of  sialic acid(one of the sugars that make up glycans) with a type of chemical handle.
• Method: Attach a fluorescent molecule to the chemical  handle, and the emitted light would reveal where the glycans were in the cell.To accomplish the above reaction chemical handle should not react with any other substance in the cell.Her quest for  optimal chemical handle ended with an azide.
• In 2000, Dr. Bertozzi modified the Staudinger reaction and used it to connect a fluorescent molecule to the azide introduced to glycans in cells. 
• If the alkyne is forced into a ring-shaped chemical structure then azides and alkynes can react in an almost explosive manner without copper as a catalyst. This reaction worked well in cells as the strain produces enough energy for the reaction to run smoothly. 
• In 2004, Dr. Bertozzi demonstrated that copper-free click reaction, called the strain-promoted alkyne-azide cycloaddition (SPAAC)  can be used to track glycans.
• Bertozzi expanded click chemistry and demonstrated how it might be used in living things. She discovered a mechanism to create a copper-free (copper is poisonous to living cells) click reaction known as the strain-promoted azide-alkyne cycloaddition and showed that it might be utilised to treat tumours.
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                                                                                              Image Credit: The Royal Swedish Academy of Sciences

Applications of Click Chemistry

• Applications in areas such as  drug conjugation, materials science, etc because of high selectivity and specificity of click chemistry reactions.
• Since bioorthogonal reactions do not interact with any other substances around them. So, they are extremely significant in medicinal biochemistry.
• Creation of new pharmaceuticals by Dr. Bertozzi through bioorthogonal chemistry:Through click reactions she worked on a  new pharmaceutical by joining a glycan-specific antibody to enzymes that break down the glycans on the surface of the tumour cells. 
• Applications in medicinal and materials chemistry: Research paper demonstration by John E. Moses and Adam D. Moorhouse shows that click chemistry can solve problems of purification and separation of impure products in the synthesis of dendrimers.
• Bertozzi’s methods are helpful in the development of Cancer drugs as her approach  has shown the promise of treating advanced cancer. 

Article:

1.A synthetic click: On 2022 Chemistry Nobel

2.Nobel Prize 2022: Making chemistry click

3.Explained | The research in click and bioorthogonal chemistry that led to the 2022 Nobel Prize in the field.

Article Link:

1.https://www.thehindu.com/opinion/editorial/a-synthetic-click-the-hindu-editorial-on-the-2022-nobel-prize-in-chemistry/article65980953.ece 

2.https://indianexpress.com/article/explained/explained-sci-tech/nobel-prize-2022-making-chemistry-click-8191930/ 

3.https://www.thehindu.com/sci-tech/science/explained-research-in-click-and-bioorthogonal-chemistry-that-led-to-the-2022-nobel-prize-in-the-field/article65972562.ece

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