Copper Uncaged

Caged-copper complexes that release their metal cargo on cue may help scientists explore how this essential yet toxic transition metal is trafficked and utilized in cells (J. Am. Chem. Soc., DOI: 10.1021/ja8047442). Katherine J. Franz and coworkers at Duke University envision that their caged-copper strategy also could be harnessed to kill cancer cells. That's because the method could permit precise site- and time-dependent delivery of the metal, which promotes the formation of toxic reactive oxygen species that can lead to cell death. To make the caged complexes, the researchers embedded a photoactive nitrophenyl group into the backbone of a nitrogen-rich tetradentate copper-chelating compound. Upon exposure to ultraviolet light, the chelator's backbone breaks in two, uncaging the copper (shown). Although the chelator grips copper with picomolar affinity, that might not be tight enough to keep biological copper-binding proteins from making off with the copper. So Franz's team is now working to improve the stability of caged-copper complexes and to ensure that they can be delivered to their desired cellular destinations.