In light of the recent Nobel prize award in chemistry, Kevin Boyle discusses an advance that could potentially change how chemistry is carried out in the future with far reaching applications.
On the 5th October 2022, the revolutionary concept of click chemistry was thrown into the limelight. The 2022 Nobel prize for chemistry was shared between Professor Barry Sharpless (Scripps Research, California (his 2nd Nobel prize)), Professor Morton Meldal (University of Copenhagen, Denmark), and Professor Carolyn Bertozzi (Stanford University, California). All three researchers had been working independently on click chemistry over the past 20 years or so.
The concept is simple: take two molecules and join them together; a bit like fastening a seatbelt – click! Why is this so revolutionary? Making molecules in a laboratory has never been anywhere close to that easy for the past two hundred years! Some experts have gone as far to say that it is about to change the world.
The idea began in the late 90s when Sharpless postulated that organic chemistry had become overly complicated, particularly in the field of drug synthesis. He wanted something quicker, more reliable and efficient than traditional methods, resulting in a versatile template that would allow a vast range of products to be made from a limited set of simple reactions. He also wanted something that could be as easy to carry out on an industrial scale as a small laboratory scale, which is a constant challenge chemists face.
The big breakthrough came in 2002, when Sharpless and Meldal independently published the first reaction of its kind. The product of the reaction was a triazole – a very useful nitrogen containing compound, often viewed as a chemical “building block” from which other products can be made. The triazole was, notably, the only product made. Click chemistry has of course progressed since the original discovery but the intended products are still triazoles of some description.
Sharpless’ vision has become reality. The reactions are simple, quick and versatile, producing only one product in very high amounts. At worst, additional harmless products may be produced but can be easily removed. The reactions can be done in water, and in some cases don’t require any solvent. This negates the use of a toxic organic solvent, making click-chemistry reactions environmentally friendly. They are now being used in research and industry covering many applications, such as plastics, dyes and agricultural as well as pharmaceutical products.
Where does Bertozzi fit in? Long before click chemistry was invented, Bertozzi was looking for ways to monitor the function of cells in the body; namely, “mapping” or tracking glycans (sugar molecules) that exist on the cell surface. She wanted to attach fluorescent molecules to the glycans so that she could “see” how the cells function, but was having problems with the attachment part. Click chemistry solved her problem. She called this application of click chemistry within a living cell: “bioorthogonal chemistry”. The beauty of click chemistry is that it occurs without disrupting the natural function of the cell. Her methods are now used worldwide to map the function of cells.
Using the biological markers, Bertozzi’s research group discovered that glycans protect tumour cells from the immune system. From this, she has developed antibodies (an important type of molecule in the immune system) that break down the glycans, with the intention to kill the tumour cells. The antibodies are now being tested in clinical trials as a treatment for cancer and other researchers are using a similar method to target different diseases.
It is not a wild claim to say that the work of Sharpless, Meldal and Bertozzi is genius. They believe that click chemistry is still in its infancy, a whole world of possibilities awaits. It really does seem like the start of something extraordinarily exciting.
Written by Kevin Boyle and edited by Natasha Kisseroudis.
Kevin studied Chemistry as an undergrad and later pursued a PhD in Organic Chemistry at the University of Edinburgh before later undertaking a Masters in Chemical Biology at Imperial College London. He now works as a full-time Chemistry tutor.
https://www.nobelprize.org/prizes/chemistry/2022/press-release/
https://phys.org/news/2022-10-click-chemistry-nobel-winning-science-world.html
nice article.thanks