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

preprint
submitted on 22.03.2019 and posted on 25.03.2019 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.

Funding

NSF CHE‐0955361

History

Email Address of Submitting Author

scburdette@wpi.edu

Institution

Worcester Polytechnic Institute

Country

United States

ORCID For Submitting Author

0000-0002-2176-0776

Declaration of Conflict of Interest

None

Exports