Increasing the dynamic range of metal ion affinity changes in Zn2+ photocages using multiple nitrobenzyl groups

Two generations of DiCast photocages that exhibit light-induced decreases in metal ion affinity have been prepared and characterized. Expansion of the common Zn(2+) chelator of N,N-dipicolylaniline (DPA) to include additional aniline ligand provides N,N'-diphenyl-N,N'-bis(pyridin-2-ylmethyl)ethane-1,2-diamine, a tetradentate ligand that was functionalized with two photolabile groups to afford DiCast-1. Uncaging of the nitrobenzhydrol reduces the electron density on two metal-bound aniline ligands, which decreases the Zn(2+) affinity 190-fold. The analogous MonoCast photocage with a single nitrobenzhydrol group only undergoes a 14-fold reduction in affinity after an identical photochemical transformation. A second series of DiCast photocages based on a N,N'-(pyridine-2,6-diylbis(methylene))dianiline scaffold, which allows the introduction of two additional Zn(2+)-binding ligands into a preorganized chelator, expand on the multi-photolabile group strategy. DiCast-2 includes two pyridine ligands while DiCast-3 adds two carboxylate groups. Addition of bridging pyridine to the second generation photocages leads to more stable Zn(2+) complexes, and photolysis of two photolabile groups increases the Zn(2+) affinity changes to 480-fold. The Zn(2+), Cu(2+), and Cd(2+) binding properties were examined in all the DiCast photocages and the corresponding photoproducts using UV-vis spectroscopy. Further insight into the photocage Zn(2+)-binding motifs was obtained by X-ray analysis of DiCast-2 and DiCast-3 model ligands.