Bertozzi: bioorthogonal & click chemistry out of curiosity

A sum-up Lecture on bioorthogonal chemistry by Bertozzi@ Kavli Foundation during ACS Spring 2012 National Meeting in San Diego on March 26, 2012.

"Bioorthogonal chemistry is literally chemistry for life"

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. 

                                

Stability & reactivity, copper-free click chemistry

JACS 2012, Angew. Chem. Int. Ed. 2012, 51, 2443


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