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

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

Digital circuits and neural networks based on acid-base chemistry implemented by robotic fluid handling

The complementarity of acids and bases is a fundamental chemical concept. Here, the authors use simple acid-base chemistry to encode binary information and perform information processing including digital circuits and neural networks using robotic fluid handling