Scripps Research Institute Chemists Uncover Powerful New Click Chemistry Reactivity

Nobel laureate K. Barry Sharpless at The Scripps Research Institute (TSRI)
Nobel laureate K. Barry Sharpless at The Scripps Research Institute (TSRI)
The findings open a doorway on an unexplored chemical galaxy containing vast numbers of new molecules for making drugs, plastics and unprecedented smart materials

Chemists led by Nobel laureate K. Barry Sharpless at The Scripps Research Institute (TSRI) have used his click chemistry to uncover unprecedented, powerful reactivity for making new drugs, diagnostics, plastics, smart materials and many other products.

The new SuFEx—Sulfur Fluoride Exchange—reactions enable chemists to link molecules of their choice together using derivatives of a common commercial chemical considered essentially inert. The Sharpless team made this chemical reliably and predictably reactive. Astonishingly, acid-base constraints are rarely a concern, though they are central to nature’s chemistry and an enormous hurdle for chemists. The stabile linkers are also non-polar and can enter cells, so have potential for crossing the blood-brain barrier.

Consequently, SuFEx gives easy access to an entire, unexplored galaxy within the chemical universe.

“This is a new, emergent phenomenon,” said Sharpless, the W.M. Keck Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI.

Click chemistry, conceived in the mid-90s as a method for discovering new and improving existing chemical reactivity, became universally used in the chemical sciences after the 2002 discovery of copper-catalyzed azide-alkyne cycloaddition (CuAAC). Now SuFEx is the second “perfect” click reaction to be discovered at TSRI.

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