These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
2 files

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

submitted on 22.03.2019, 13:25 and posted on 25.03.2019, 16:52 by Prem N. Basa, Chelsea A Barr, Kady M Oakley, Xiaomeng Liang, Shawn Burdette
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.


NSF CHE‐0955361


Email Address of Submitting Author


Worcester Polytechnic Institute


United States

ORCID For Submitting Author


Declaration of Conflict of Interest