Click chemistry reaction thrown into reverse using ultrasound could lead to new protection strategies
US chemists have attached polymer chains to a small, robust molecule and used ultrasound to grab the chains and literally pull the molecule apart. The technique can reverse click chemistry reactions, a popular transformation in which simple starting materials are snapped together under mild conditions. Reversing this process, or ’unclicking’ the components, could be used to activate covalent bonds in a manner that is inaccessible through thermal or photochemical treatments.
In their demonstration of a mechanically facilitated reaction, Christopher Bielawski and colleagues at the University of Texas at Austin, focused on the highly inert 1,2,3-triazole moiety. These molecules are readily made using click chemistry by coupling an azide and alkyne, but the team reasoned the same triazole might be a useful protecting group in various chemical processes if there were a way to reverse the process. Given that light and heat are inadequate, the team turned to a mechanical alternative for this cycloreversion.
By incorporating the triazole group into poly(methyl acrylate) (PMA) the researchers could give it hooks which can be used to direct mechanical forces. It is known that polymers can be pulled apart using ultrasound. Ultrasound causes nucleation, growth and collapse of bubbles in solution. A solvated polymer chain close to a cavitating bubble will be stretched to breaking point. Bielawski’s group exploited this phenomenon to pull apart triazoles that are part of PMA chains.
The team points out that unclicking triazoles in this way opens up new ways of using their constituent azides and alkynes and might allow for the use of triazoles as mechanically labile protecting groups in synthetic reactions. For example, triazoles could potentially be used to protect azides from harsh environments required to build another part of the same molecule. After the desired reaction has taken place, mechanical force could then be used to liberate the azide, which can then be used for further chemical modification. The methodology might also be used in the development of dye-sensitised force sensors or in force-responsive fluorescent tags for biological assays.
According to Craig Hawker of University of California, Santa Barbara, US, the research might change the way chemists make and break covalent bonds, giving them a new paradigm for preparing organic molecules. ’Being able to literally pull apart these triazoles into their constituent precursors and then unlock their chemical reactivity in new ways is now possible with the assistance of mechanical force,’ he says. ’This approach might then be coupled to traditional strategies for covalent bond formation.’
J N Brantley, K M Wiggins and C W Bielawski, 333, 1606 (DOI: 10.1126/science.1207934)