Kien Nguyen Huy Trung
CLICK CHEMISTRY AND BIOORTHOGONAL CHEMISTRY
I. Award:
The Royal Swedish Academy of Sciences awarded the 2022 Nobel Prize in Chemistry to Carolyn R. Bertozzi, Morten Meldal and K. Barry Sharpless “for the development of click chemistry and bioorthogonal chemistry”.
II. About 2022 Nobel Prize in Chemistry:
The theme of the 2022 Nobel Prize in Chemistry is the simplification of complex processes. Barry Sharpless and Morten Meldal are the pioneers laying the groundwork for click chemistry, a powerful field that quickly and efficiently assembles building blocks of molecules. Carolyn Bertozzi has taken click chemistry to the next level and applied it to living things.
III. The history of click chemistry and bioorthogonal chemistry:
For a long time, chemists’ motivation has always been to build more complex molecules. In pharmaceutical research, this often requires the artificial synthesis of natural molecules with medicinal properties. This has given rise to many admirable synthesis methods, but they are often costly and time-consuming. Around the turn of this millennium, Barry Sharpless – a second recipient of the Nobel Prize in Chemistry – formulated the concept of click chemistry, a simple and reliable field that uses very fast reactions and avoids the formation of by-products.
Not long after, Morten Meldal and Barry Sharpless independently discovered the “jewel” of click chemistry: the copper-catalyzed azid-alkyn ring addition reaction (Fig.1) This is a subtle and effective transformation that is being widely used . Among its applications are drug development, DNA mapping, and the creation of more suitable drugs. Carolyn Bertozzi is the one who takes click chemistry to the next level. To detect important but hard-to-locate biomolecules on the surface of cells – glycans – she developed a click reaction in organisms. The course of these orthogonal reactions does not disturb the cell chemistry.
Fig.1
Source: ©The Royal Swedish Academy of Sciences
These reactions have been used globally to explore cell structure and trace biological processes. Thanks to orthogonal bioreactors, the researchers have developed the ability to localise the cancer drug, progressing in clinical trials. Click chemistry and orthogonal bioreactions brought about the era of functionalism in chemistry. This is of great benefit to all mankind.
IV. About bioorthogonal chemistry:
The general idea would be a “click reaction” between an azid (which is functionalized to a glycan) and an alkyn (which fluoresces). The alkyne chosen is the cyclooctyn, which is the smallest cycloalkyn formed to date and has a high ring tension, so the reaction proceeds smoothly without copper catalysis. This is a necessary step towards being non-toxic to cells and organisms. Metabolism is so rapid that it completely ignores other chemical regions in the physiological environment, perhaps hence the name “bioorthogonal” (Fig.2).
Source: ©The Royal Swedish Academy of Sciences
Image reference:
The Nobel Prize in Chemistry 2022. NobelPrize.org. Nobel Prize Outreach AB 2022. Fri. 14 Oct 2022. <https://www.nobelprize.org/prizes/chemistry/2022/summary/>