Thiol-yne click chemistry

Sounds familiar? "A perusal of the literature from 1940s to 1960s" prompted this new version of click chemistry.

As indicated in the scheme, the double thiol-addition happens in two consecutive steps with the second 3-times faster than the first. The reaction can be driven either by light or radical initiators. Not only it complements established click chemistries such as alkyne-azide and thiol-ene, but also it provides a new feature which enables installation of more functional groups at once. This click chemistry was demonstrated with a few recent examples, either individually or in combination with other click chemitries. It is best suited for construction of dendrimers, networked structures, polymers, and other functional materials. I would expect it to find applications in biotechnology, nanotechnology, surface chemistry,  etc. 

Andrew B. Lowe et al, J. Mater. Chem., 2010, DOI: 10.1039/b917102a
      

Bioorthogonal click chemistry - Carolyn Bertozzi the champion

Chem. Soc. Rev., 2010 DOI: 10.1039/b901970g

Carolyn Bertozzi et al clearly defined the bioorthognal click chemistry. They used this figure to illustrate a general bioorthogonal reaction. Best described: "we must first look at an organic chemistry textbook and remove any reaction that is sensitive to water. Second, with an abundant supply of thiols and amines in the cell, we must also remove reagents that are prone to nucleophilic attack. Third, because of the reducing environment in the cytosol, we have to remove reactions that are sensitive to redox chemistry. If a reaction requires heat (above 37 °C), pressure, or high concentrations to work then it is also unacceptable. Lastly, some functionalities can be digested by cellular enzymes that have an ase in their name (e.g., esterase, phosphatase, sulfatase, etc.). Add reagent toxicity to this list and you will find a select few reactions that remain viable for performance in living systems."

Indeed one needs to be very picky in picking a good bioothogonal reaction from the already- small click chemistry tool box. The review covers the most viable reactions up-to-date, lists their pros and cons, and potentials. The chemistry aspects are detailed, with great insights and perspectives from a mechanistic point of view.

And did I mention the secret - go back to the old dusty organic chemistry toolbox and find treasures, such as click chemistry?