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

25 March 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Photocaged complexes have demonstrated efficacy as tools to control the availability of bioactive metals in cells to interrogate signaling pathways. We describe the synthesis of two new photocages, {bis[(2-pyridyl)methyl]amino}(9-oxo-2-xanthenyl)acetic acid (XDPAdeCage, 1) {bis[(2-pyridyl)methyl]amino}(m-nitrophenyl)acetic acid (DPAdeCage, 2), which utilize a 4-xanthone acetic acid and meta-nitrobenzyl chromophore respectively, to mediate a photodecarboxylation reaction. Both photocages strongly coordinate Zn2+ and the binding equilibrium shifts significantly toward free Zn2+ upon the decarboxylation of the chelator. XDPAdeCage photolyzes with quantum yield of 27% with 365 nm light, and binds Zn2+ with 4.6 pM affinity, which decreases by over 4 orders of magnitude upon uncaging. A neutral form of [Zn(XDPAdeCage)]+ can be generated in situ using the anionic bidentate ligand pyrithione, which imparts membrane impermeability to the ternary complex. Using fluorescent imaging, we have confirmed transport of Zn2+ across lipophilic membranes; in addition, RT-PCR experiments demonstrate the photocaged complexes ability to perturb cellular processes after photolysis by showing a change in the expression levels of metallothionein and zinc transporter proteins.



Supplementary materials

March 22 SI


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.