The design and synthesis of aromatic crystalline materials with controllable crystal structure packing is of particular interest in organic semiconductor and optoelectronic devices, where 1-D π−π stacked structures that enhance charge mobility are the most beneficial. We report here that the π−π interactions between aromatic molecules can be strengthened and the C sp2 −H···π (T−shape) interaction can be suppressed by perfluoroalkylation of corresponding aromatics. Both crystal structure data and ab initio calculations show that the π−π interaction is strengthened due to the electronic effects of perfluoroalkyl substituents, and the C sp2 −H···π interaction is suppressed by the steric effects of the perfluoroalkyl substituents. The C sp3 −F···F−C sp3 attractive interactions between perfluoroalkyl chains further stabilize the crystal structures. We also found that C sp3 −F···π interaction can be eliminated if an optimal electron deficiency of the π system is tuned by adjusting the number of perfluoroalkyl substituents. The insight gained from this study is of particular interest in organic semiconductor research as well as the fields of molecular recognition, sensing, and design of enzyme inhibitors where π−π interactions are also important.

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 Zn 2+ and the binding equilibrium shifts significantly toward free Zn 2+ upon the decarboxylation of the chelator. XDPAdeCage photolyzes with quantum yield of 27% with 365 nm light, and binds Zn 2+ 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 Zn 2+ 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. File list (2) download file view on ChemRxiv March_22 Manuscript.pdf (734.69 KiB) download file view on ChemRxiv March_22 SI.pdf (5.45 MiB)

Metal ion signaling in biology has been studied extensively with ortho-nitrobenzyl photocages; however, the low quantum yields and other optical properties are not ideal for these applications. We describe the synthesis and characterization of NTAdeCage, the first member in a new class of Zn2+ photocages that utilizes a light-driven decarboxylation reaction in the metal ion release mechanism. NTAdeCage binds Zn2+ with sub-pm affinity using a modified nitrilotriacetate chelator and exhibits an almost 6 order of magnitude decrease in metal binding affinity upon uncaging. In contrast to other metal ion photocages, NTAdeCage and the corresponding Zn2+ complex undergo efficient photolysis with quantum yields approaching 30%. The ability of NTAdeCage to mediate the uptake of 65Zn2+ by Xenopus laevis oocytes expressing hZIP4 demonstrates the viability of this photocaging strategy to execute biological assays.

Site-selective imination of anthraquinone-based macrocyclic crown ethers using titanium tetrachloride as the catalyst yields imines where only the external carbonyl group of the anthraquinone forms Schiff-bases. The following aromatic amines yield monomeric compounds (aniline, 4-nitroaniline, 4-pyrrolaniline, and 1,3-phenylenediamine). Reaction of 2 equiv of the macrocyclic anthraquinone host with 1,2- and 1,4-phenylenediamine yields dimeric imine compounds. The 1,2-diimino host acts as a luminescence sensor, exhibiting enhanced selectivity for Ba(II) ion. Spectroscopic data indicate that two barium ions coordinate to the sensor. Due to E/Z isomerization of the imine, the monomeric complexes are nonluminescent. Restricted rotation about the 1,2 oriented C═N groups or other noncovalent/coordinate-covalent interactions acting between neighboring crown ether rings may inhibit E/Z isomerization in this example, which is different from current examples that employ coordination of a metal cation with a chelating imine nitrogen atom to suppress E/Z isomerization and activate luminescence. The 1,4-diimino adduct, where the crown rings remain widely separated, remains nonluminescent.

Selective reduction of an anthracenone-quinoline imine derivative, 2, using 1.0 equiv of NaBH(4) in 95% ethanol affords the corresponding anthracen-9-ol derivative, 3, as confirmed by (1)H NMR, (13)C NMR, ESI-MS, FTIR, and elemental analysis results. UV-vis and fluorescence data reveal dramatic spectroscopic changes in the presence of Zn(II) and Cu(II). Zinc(II) coordination induces a 1,5-prototropic shift resulting in anthracene fluorophore formation via an imine-enamine tautomerization pathway. Copper(II) induces a colorimetric change from pale yellow to orange-red and results in imine hydrolysis in the presence of water. Spectroscopic investigations of metal ion response, selectivity, stoichiometry, and competition studies all suggest the proposed mechanisms. ESI-MS analysis, FTIR, and single-crystal XRD further support the hydrolysis phenomenon. This is a rare case of a single sensor that can be used either as a chemosensor (reversibly in the case of Zn(II)) or as a chemodosimeter (irreversibly in the case of Cu(II)); however, the imine must contain a coordinating Lewis base, such as quinoline, to be active for Cu(II).

Metal ion signaling in biology has been studied extensively with ortho-nitrobenzyl photocages; however, the low quantum yields and other optical properties are not ideal for these applications. We describe the synthesis and characterization of NTAdeCage, the first member in a new class of Zn 2+ photocages that utilizes a light-driven decarboxylation reaction in the metal ion release mechanism. NTAdeCage binds Zn 2+ with sub-pM affinity using a modified nitrilotriacetate chelator and exhibits an almost 6 order of magnitude decrease in metal binding affinity upon uncaging. In contrast to other metal ion photocages, NTAdeCage and the corresponding Zn 2+ complex undergo efficient photolysis with quantum yields approaching 30%. The ability of NTAdeCage to mediate the uptake of 65 Zn 2+ by Xenopus laevis oocytes expressing hZIP4 demonstrates the viability of this photocaging strategy to execute biological assays. Keywords cage compounds; coordination compounds; photolysis; X-ray diffraction; zinc The importance of Zn 2+ beyond structural and catalytic functions in proteins has become increasingly apparent. [1] Zinc and iron regulated proteins (ZIPs) increase cytosolic Zn 2+ concentrations; in contrast, zinc transporter (ZnT) proteins decrease cytosolic Zn 2+ . [2,3] Elucidating the function of free or loosely bound Zn 2+ in the cytosol as well as in intracellular compartments remains important; however, the ability to modulate Zn 2+ levels in vivo in a time-resolved manner remains elusive. [4] Free Zn 2+ has been implicated in various signaling pathways, [1] and recently fertilization of oocytes has been shown to trigger "zinc sparks" that serve to initiate meiosis at the beginning stages of embryotic development. [5] The development of new methodologies to simulate fluctuations in Zn 2+ concentrations in a spatiotemporal manner would facilitate the understanding of complex signaling processes.Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201505778. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe photochemistry of ortho-nitrobenzyl (oNB) chromophores initially was recognized as a means to deliver Ca 2+ in a controlled manner to biological receptors using light. [6] We subsequently adapted two Ca 2+ -releasing strategies to develop photocaged complexes for biologically relevant metal ions such as Zn 2+ , Cu + and Fe 3+ . [7,8] In the Cast photocages, decreased electron density on a coordinated aniline nitrogen atom following photolysis lowers chelator binding affinity. [9][10][11] While this strategy can adequately buffer Ca 2+ at typical intracellular resting levels (ca. 100 nM) and simulate biologically relevant concentration increases, [6,12] the reliance on weakly coordinating aniline-based ligands precludes use with Zn 2+ , which experiences tighter intracellular homeostasis. [11] Alternatively, photolytically breaking a carbon-heteroatom bond provides compounds that release metal ions through the reduction ...

Reduction of imine-anthracenone compounds selectively produces secondary alcohols leaving the external imine group unreacted. Addition of the Zn(II) ion induces a metal-mediated imine-enamine tautomerization reaction that is selective for Zn(II), a new fluorescence detection method not previously observed for this important cation.

Self-assembly enables formation of incredibly diverse supramolecular structures with practically important functions from simple and inexpensive building blocks. Here, we show how a semirational, bottom-up approach to create emerging properties can be extended to a design of highly enantioselective catalytic nanoassemblies. The designed peptides comprising as few as two amino acid residues spontaneously self-assemble in the presence of metal ions to form supramolecular, vesicle-like nanoassemblies that promote transfer hydrogenation of ketones in an aqueous phase with excellent conversion rates and enantioselectivities (>90% ee).