Powerful new click chemistry reactivity

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 SuFExSulfur Fluoride Exchangereactions 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.

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.

Life chemistry depends on phosphate and amide linkers which are polar, so constrained when entering or exiting cells and membranes. During its three billion-year adventure, nature never adopted sulfate links, yet SuFEx has been shown to be tolerated by and within the chemistry of life.

The breakthrough came by making SO2F2 reactive. SO2F2 is the commercial gas known as Vikane, the world's most common fumigant, used for tenting buildings to kill termites, as well as being pumped into vast warehouses to rid produce of potential disease vectors and extend shelf life.

One of the most exciting potential uses of SuFEx is the promise of finding new diagnostics, drugs and other therapeutics, even ones reactive within the human body.

TSRI chemists are already using SuFEx reactivity for the precision assembly of new molecules from diverse building blocks. This should quickly lead to reduced manufacturing costs for equivalents of existing products, as well as the introduction of new products made by easy synthetic routes.

We believe that we can, with near-perfect control, use sulfur fluorides as general connectors for joining molecular building blocks, said Dong.

The reaction easily creates polysulfate plastics, a whole class of unexplored of materials .Polysulfate plastics may, for example, have properties to rival or surpass those of popular, ubiquitous polymers like polycarbonates. Strong, resilient and transparent, polycarbonates are annually produced in the millions of tons and are found everywhere in consumer products, from DVDs to the cockpit canopies of F-22 Raptor jets. Yet polycarbonates hydrolizebreak down in waterrather easily. A consequence is the much-publicized leaching of bis-phenol-A, the principal building block of all polycarbonates and an estrogen mimic.

A stable, non-leaching commercial polysulfate is an obvious target for SuFEx. Chemists have long assumed polysulfates could not be made by a commercially feasible method, but in a strikingly easy, controlled and scalable process, the Sharpless team made BPA polysulfate fibers.

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Powerful new click chemistry reactivity