Zinc Photocages with Improved Photophysical Properties and Cell Permeability Imparted by Ternary Complex Formation

Photocaged complexes can control the availability of metal ions to interrogate cellular signaling pathways. We describe a new photocage, {bis[(2-pyridyl)methyl]amino}(9-oxo-2-xanthenyl)acetic acid (XDPAdeCage, 1), which utilizes a 2-xanthone acetic acid group to mediate a photodecarboxylation reaction. XDPAdeCage photolyzes with a quantum yield of 27%, and binds Zn2+ with 4.6 pM affinity, which decreases by over 4 orders of magnitude after photolysis. For comparison to our previous approach to Zn2+ release via photodecarboxylation, the analogous photocage {bis[(2-pyridyl)methyl]amino}(m-nitrophenyl)acetic acid (DPAdeCage, 2), which uses a m-nitrobenzyl chromophore, was also prepared and characterized. The advantages of the 2-xanthone acetic acid chromophore include red-shifted excitation and a higher extinction coefficient at the preferred uncaging wavelength. The neutral ternary complex of [Zn(XDPAdeCage)](+) with the anionic ligand pyrithione is membrane permeable, which circumvents the need to utilize invasive techniques to introduce intracellular Zn2+ fluctuations. Using fluorescent imaging, we have confirmed transport of Zn2+ across membranes; in addition, RT-PCR experiments demonstrate changes in expression of Zn2+-responsive proteins after photolysis.