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K. Barry Sharpless - Chemistry's 'Influencer'

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Before the term “influencer” became synonymous with celebrity endorsements on social media, it could most assuredly have been a moniker to be applied to K. Barry Sharpless within the chemistry community. 

Earlier this month, Sharpless joined the exclusive club of two-time Nobel prize winners. His latest Nobel laureate status has been awarded for his pioneering work (along with that of Carolyn Bertozzi and Morten Meldal) in “click chemistry” and adds to the Nobel prize he won in 2001 for his work in the field of asymmetric catalysis. He is now in the rarefied company of only four other two-time winners – Marie Curie (1902 for Physics and 1911 for Chemistry); Linus Pauling (1954 for Chemistry and 1962 for Peace); John Bardeen (1956 and 1972 – both for Physics) and Frederick Sanger (1958 and 1980 – both for Chemistry).

His first seminal area of research (and for which he garnered his 2001 laureate) was in the area of asymmetric catalysis – specifically asymmetric oxidation processes. The Sharpless epoxidation, Sharpless asymmetric dihydroxylation and Sharpless oxyamination enable organic chemists to stereoselectively introduce additional functionality into pro-chiral molecules. Single stereoisomer chiral molecules constitute well over half the number of currently marketed small molecule drugs. Making these via asymmetric catalytic methods avoids the need for tedious (and often expensive) resolution processes or the need to recycle or dispose of the unwanted stereoisomer(s). Sharpless’ work opened up the door through which many others subsequently followed whereby asymmetric catalysis has become relatively routine for most organic chemists working in the pharmaceutical industry.

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His more recent honor by the Nobel Committee, was for the development of reactions that are fast, simple to use, easy to purify, versatile, regiospecific, and give high product yields. They are characterized by a high thermodynamic driving force that drives the reactants to “click” together to form the product – hence the term Click Chemistry. Such reactions are particularly sought after by the pharmaceutical community for their tolerance of typical biological conditions, tolerance of most functional groups and the ability to run them in (or on) water. The development of Click Chemistry opens up the possibility of easier, more modular drug synthesis where specific fragments can be easily “clicked” together to form the target molecule of choice. Furthermore, Click Chemistry has found application in biomedical imaging, development of non-viral drug delivery vectors and drug conjugation.

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Given the breadth of impact of his technologies and approaches, it could be credibly argued that Sharpless has been the single greatest influencer of recent decades on drug discovery and CMC in the 21st century.  

As Dawn Kelly, Functional Lead of Chemistry at APC says, “Barry Sharpless’ ability to conceptualize how chemistry should work and then develop methods of making it work that way has had an astounding impact on modern chemistry”.  

In an interview on the day his 2022 prize was announced he was already talking about his “next idea” which he said, “is pretty good I think”. Ever the master of understatement, who’s to say that this next idea (whatever it is) will not be equally as influential as his previous ones!