Carbon Dioxide Radical Anion by Photoinduced Equilibration between Formate Salts and [11C, 13C, 14C]CO2: Application to Carbon Isotope Radiolabeling

The need for carbon-labeled radiotracersis increasinglyhigherin drug discovery and development (carbon-14, & beta;(-), t (1/2) = 5730 years) as well as in positronemission tomography (PET) for in vivo molecular imaging applications(carbon-11, & beta;(+), t (1/2) =20.4 min). However, the structural diversity of radiotracers is stillsystematically driven by the narrow available labeled sources andmethodologies. In this context, the emergence of carbon dioxide radicalanion chemistry might set forth potential unexplored opportunities.Based on a dynamic isotopic equilibration between formate salts and[C-13, C-14, C-11]CO2, C-labeledradical anion CO2 (& BULL;-) could be accessedunder extremely mild conditions within seconds. This methodology wassuccessfully applied to hydrocarboxylation and dicarboxylation reactionsin late-stage carbon isotope labeling of pharmaceutically relevantcompounds. The relevance of the method in applied radiochemistry wasshowcased by the whole-body PET biodistribution profile of [C-11]oxaprozin in mice.