“Chemistry for Life”, one hundred young researchers have been chosen in this unique experience to interact with the 6 Nobel laureates: Sidney Altman, Ryoji Noyori, Barry Sharpless, Aaron Ciechanover, Richard R. Schrock and Ada E. Yonath. Also there were the leaders and scientists from industrial world.
A talk by Barry Sharpless covers many topics including click chemistry. Many seemingly random and scattered thoughts may better be heart-felt when one has gained quite some experience into the research career. Say, illusions, astronomical number of possible compounds, function, fishing, on-water reactions, German chemistry tradition, the huge wealth of chemistry in place today, Invitrogen Click-It, etc.
Bioorthogonal chemistry and click chemistry owe the debt to the curiosity-driven rather than problem-driven discoveries by two German scientists, Hermann Staudinger & Rolf Huisgen, nearly a century ago. "Without some curiosity-driven research we won't leave much of a legacy for the next generation of scientists".
Bertozzie coined bioorthogonal chemistry decade ago to probe "biomolecules within their native habitats, that is, in cells, or even better, live organisms". The group developed first bioorthogonal reaction, Staudinger ligation, slow for most biological processes. Sharpless CuACC is 25 times faster than Staudinger but with copper toxicity. Copper-free click chemistry, DIFO, combines biocompatibility of Staudinger ligation with fast kinetics of triazol click chemistry.
A contribution from Bertozzi group, on the stability and reactivity of cycloalkynes
Bioorthogaonal chemistry: stable while fast reacting in highly functionalized environment Rapid reaction kinetics, high specificity, good stability, low side-reactivity activating vs deactivatiing modifications: ring size (relaxing or strain), electronic factors (electron with-drawing, hybridization patterns), stabilizing large atoms as sulfur / Silicon etc. Cu-free click chemistry, cycloaddition between azides and cyclooctynes Stability and reactivity can be fine-tuned