The Nobel Prize in Chemistry has been awarded to three
this year. Professor Carolyn R. Bertozzi of Stanford University, Scripps
Laboratory Professor Karl Barry Sharpless, and Professor Morten P. Meldal of
Copenhagen University.1
Among them, Prof. Sharpless was awarded Nobel Prize for the
second time. So far, five people have received the Nobel Prize twice. His first
Nobel was in 2001 for discovering a catalytic way to make molecules that do not
overlap when placed on each other, like left and right hands. His name is the
prefix of that reaction: Sharpless epoxidation.2
In April, a year after Nobel Prize, Prof. Sharpless communicated
the results of his other work.3 The same year, Prof. Meldel's
research dealing with solid phase synthesis was also published in an another journal.4
A chemical reaction discovered by Rolf Huisgen5 in the nineteenth
century, though it is celebrated for the importance of the product it
generates, kept chemists away because of the danger in handling one reactant,
azide. Sharpless and Meldel used copper as a catalyst to reduce the reaction
temperature and the fear of handling azides. If Sharpless's discovery was a
journey of research toward a decisive conclusion, Meldel's discovery was a
journey that followed a reaction that yielded an unexpected result. But both
minds attained the same result: Another reaction with wide application in
various streams, a reaction that gives no by-products at the end, a reaction
that is not affected by extraneous factors such as water and oxygen. Most
importantly, a reaction produces only one product out of two possibilities.
In an interview after his second Nobel, Prof. Sharpless
says: “In a perfect reaction you don’t have side products. When the copper
catalyzed reaction dropped into our lab we were surprised. You put the
reactants together and collect 100% of the product and one can have this reaction in
blood, soup, urine, acid and base.” 6
 |
Figure 1:
Click chemistry © Johan Jarnestad / The
Royal Swedish Academy of Sciences |
Chemists call it 'click chemistry.' What is that prefix?
Like the sound at the Basho's Haiku, 'old pond'? Is it the sound same as the
jump of a frog in water? Or the click of a seat belt? When two molecules come
closer in the presence of copper ion, an instantaneous reaction is similar to a
click, but without any sound! Just as opposite poles of magnets stick together,
the alkyne reacts with the azide to form a ring called 'triazole.' Because of
the inert nature of the starting materials, the strength of this triazole bond
which locks two of them and selectivity, we are reaping the benefits of this
reaction today in the fields of medicine and materials. The molecules attained
through this reaction are used as drugs for diabetes, cancer, HIV, and
Alzheimer's disease, diagnostic studies, and to visualize cells. Bertozzi made
it possible to carry this click reaction from the laboratory to living cells. That
path is called ‘Bioorthogonal chemistry.’ What is it?
Bioorthogonal chemistry is the branch that performs
required reactions at faster rates under physiological conditions and is inert
to other functionalities in living cells.7 It is difficult to
perform a chemical reaction on living cells for attaching a fluorescent molecule
without harming them. Often cell functions are affected by chemicals or
functionalities of chemicals affected by the cell environment. There can be
many reasons, like water, oxygen, and temperature. Most of the time, an
unnecessary reaction/interference harms the attempt.
 |
Figure 2:
Bioorthogonal chemistry © Johan Jarnestad / The Royal Swedish Academy of
Sciences |
Bertozzi’s group worked on several chemical reactions in
cells, each of them having its own merits and demerits. It was then she read
the research papers of both the former published in 2002. She observed that
these reactions took place at room temperature catalyzed by copper in presence
of water and oxygen. But for them, the problem is copper, which kills cells. A
graduate student who worked with her discussed an article that appeared in the
nineteenth century utilizing strained rings for click chemistry without a catalyst. There is the strained ring of a compound waiting to undergo a reaction,
like a string of a bow/guitar ready to snap at any moment, like a fruit that
explodes and scatters its seeds when touched. After several attempts, they
found a strained alkyne partner capable of reacting with azides at low
temperatures. After attaching the cell with an azide-decorated sugar, they
performed the click reaction with the former. This effort, which started to visualize
cells, has expanded to deliver drugs to cells, provide beneficial bacteria in
the gut, and now has stepped into cancer treatment.
 |
Figure 3:
Bertozzi used the strain-promoted click reaction to track glycans. They have a
green glow in the picture. ©Johan Jarnestad / The
Royal Swedish Academy of Sciences |
If the above are the Chemical Science we need to discuss
on this Nobel prize, Bertozzi gives us something to discuss on Social Science:
"The early composition of my lab at Berkeley, really
the core people that did the work that the Nobel Foundation has recognized
before if you look at that group of people, they are far more diverse than
certainly at that time you would see in the average chemistry laboratory. I had
a preponderance of female grade students at that time when our representation
in the graduate program at Berkeley was maybe 30%, but my lab has over half. I
had people from different backgrounds, people who identify as underrepresented
minorities. And I think, that diversity of people created an environment where
we felt we didn't have to play by the same old rules as scientists. We could do
things like organic chemistry in living animals. Why not, right?! We didn't
have to play by the rules! If there weren't the right chemistries to get the
job done, we could invent new chemistries! Why not?! We didn't have to play by
the rules! And I think that culture, it kind of grew organically – no pun
intended – without a whole lot of steering by myself. I was very fortunate that
I could actually play a supportive role in my lab, and let that diverse group
of students find their voice, realize their curiosity, break the rules, and do
something that twenty-five years later some people found impactful. And I owe
them a great debt of gratitude."8
Its meaning becomes even more apparent when read against
the background that Bertozzi voices for inclusion and diversity in the
workplace. That is something we need to discuss in accordance with this year's
Nobel prize.
References:
1.
https://www.nobelprize.org/prizes/chemistry/2022/press-release/
2.
https://www.nobelprize.org/uploads/2018/06/advanced-chemistryprize2001.pdf
4.
https://pubs.acs.org/doi/10.1021/jo011148j
5.
https://www.nature.com/articles/s41589-020-0571-4
6.
https://www.youtube.com/watch?v=ADhhvKZAYUs&ab_channel=ScrippsResearch
7.
Bioorthogonal
Chemistry: Fishing for Selectivity in a Sea of Functionality https://onlinelibrary.wiley.com/doi/10.1002/anie.200900942
8.
https://twitter.com/malycat03/status/1578254758384611328
9.
Telephonic interview
– Sharpless https://twitter.com/NobelPrize/status/1577792412893724678
10. Telephonic interview – Meldel https://twitter.com/NobelPrize/status/1577643078265061377
11. Telephonic interview – Bertozzi https://twitter.com/NobelPrize/status/1577660360735313920
12. The illustrations are free to use for non-commercial
purposes. Attribute ”© Johan Jarnestad/The Royal Swedish Academy of
Sciences” https://www.nobelprize.org/uploads/2022/10/fig2_ke_en_22_clickReaction.pdf
13. The illustrations are free to use for non-commercial
purposes. Attribute ”© Johan Jarnestad/The Royal Swedish Academy of Sciences” https://www.nobelprize.org/uploads/2022/10/fig3_ke_en_22_bioorthogonalChemistry.pdf
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