Scripps scientists bring focus to mechanism of click reaction
The process, known as copper-catalyzed azide-alkyne cycloaddition, became a go-to method for the synthesis of drugs after scientists discovered the reaction in 2002. Despite the widespread use of the process, how the reaction worked was not precisely understood.
"Despite its many uses, the nature of the copper-containing reactive intermediates that are involved in the catalysis had not been well understood, in large part due to the promiscuous nature of copper, which rapidly engages in dynamic interactions with other molecules," Valery Fokin, a chemist and the principal investigator for the study, said.
Fokin and his colleagues published the results of a new study on Thursday in Science Express which attempted to reproduce key steps of the CuAAC catalytic cycle. The study corroborated the results of previous studies which hinted that not one but two copper-containing catalytic units were needed to build a new triazole structure.
"By monitoring the reaction in real time, we showed that both copper atoms are needed and established the involvement of copper-containing intermediates that could not be isolated or directly observed," Brady Worrell, the paper's first author, said.
A second set of experiments determined the two copper centers were effectively interchangeable during key steps of the reaction.
Fokin said the research would give scientists a better understanding of the many biological and chemical processes involving copper.
"These new findings allow us to exert greater control of the reaction and make it faster and more efficient under the most challenging conditions," Fokin said. "The reaction-tracking techniques we developed here also can be applied to the study of other complex processes, both chemical and biological."
The National Institutes of Health's National Institute of General Medical Sciences provided funding for the study.