Difference between Click Chemistry and Bioorthogonal Chemistry

Nobel Prize in Chemistry 2022 was awarded to three scientists for for the development of ‘click chemistry’ and bioorthogonal chemistry”

1.     Barry Sharpless of Scripps Research, USA, 

2.     Carolyn R. Bertozzi of Stanford University, USA and 

3.     Morten Meldal of University of Copenhagen, Denmark.

Image credit https://www.nobelprize.org/

Click Chemistry

a) The term “click chemistry” was coined by Barry Sharpless

b) Click chemistry refers to a group of reactions that are fast, simple to use, easy to purify, versatile, and give high product yields.

Combining molecules together in simple reactions forming a product without any or minimum by products or intermediate products

c) Characteristics of click reaction:  include simple reaction conditions 

• ideally, the process should be insensitive to oxygen and water,
• readily available starting materials and reagents,
• use of no solvent or water as a solvent and simple product isolation.

d) Barry Sharpless and Morten Meldal independently discovered the first click reaction copper catalysed azide-alkyne cycloaddition.

e) Wide applications in a wide variety of research areas, including materials sciences, polymer chemistry, and pharmaceutical sciences.

Bioorthogonal Chemistry

a) The term Bioorthogonal Chemistry was coined by Carolyn Bertozzi 

Image credit https://www.nobelprize.org/

b) Bioorthogonal chemistry is a set of rapid reactions that can take place in biological environments without affecting biomolecules or interfering with biochemical processes.

c) Carolyn Bertozzi developed click reactions that work inside living organisms without any toxic effects. 

d) The earliest bioorthogonal reaction developed was a modified Staudinger ligation; strain induced azide-alkyne cycloaddition; a biorthogonal reaction and  a click reaction developed by Bertozzi’s team.

d) Wide applications in imaging, identifying, and characterizing biomolecules genetic code expansion and metabolic engineering, drug target identification, antibody–drug conjugation and drug delivery.

 *copper catalysed azide-alkyne cycloaddition is not a biorthogonal reaction as copper is toxic to cells.

 

References

Scinto SL, Bilodeau DA, Hincapie R, Lee W, Nguyen SS, Xu M, Am Ende CW, Finn MG, Lang K, Lin Q, Pezacki JP, Prescher JA, Robillard MS, Fox JM. Bioorthogonal chemistry. Nat Rev Methods Primers. 2021;1:30. 

Hein CD, Liu XM, Wang D. Click chemistry, a powerful tool for pharmaceutical sciences. Pharm Res. 2008 Oct;25(10):2216-30. 

Bird, R. E., Lemmel, S. A., Yu, X., & Zhou, Q. A. (2021). Bioorthogonal chemistry and its applications. Bioconjugate Chemistry, 32(12), 2457-2479.