Probing the Ni2+ -selective Response of Fluorescent Probe NiSensor-1 with the NiCast Photocaged Complex.

CTEA (N,N-bis[2-(carboxylmethyl)thioethyl]amine) is a mixed donor ligand that has been incorporated into multiple fluorescent sensors such as NiSensor-1 that was reported to be selective for Ni2+ . Other metal ions such as Zn2+ do not produce an emission response in aqueous solution. To investigate the coordination chemistry and selectivity of this receptor, we prepared NiCast, a photocage containing the CTEA receptor. Cast photocages undergo a photoreaction that decreases electron density on a metal-bound aniline nitrogen atom, which shifts the binding equilibrium toward unbound metal ion. The unique selectivity of CTEA was examined by measuring the binding affinity of NiCast and the CTEA receptor for Ni2+ , Zn2+ , Cd2+ and Cu2+ under different conditions. In aqueous solution, Ni2+ binds more strongly to the aniline nitrogen atom than Cd2+ ; however, in CH3 CN, the change in affinity virtually disappears. The crystal structure of [Cu(CTEA)], which exhibits a Jahn-Teller-distorted square pyramidal structure, was also analyzed to gain more insight into the underlying coordination chemistry. These studies suggest that the fluorescence selectivity of NiSensor-1 in aqueous solution is due to a stronger interaction between the aniline nitrogen atom and Ni2+ compared to other divalent metal ions except Cu2+ .

Detection and Quantification of Tightly Bound Zn2+ in Blood Serum Using a Photocaged Chelator and a DNAzyme Fluorescent Sensor.

DNAzymes have emerged as a powerful class of sensors for metal ions due to their high selectivity over a wide range of metal ions, allowing for on-site and real-time detection. Despite much progress made in this area, detecting and quantifying tightly bound metal ions, such as those in the blood serum, remain a challenge because the DNAzyme sensors reported so far can detect only mobile metal ions that are accessible to bind the DNAzymes. To overcome this major limitation, we report the use of a photocaged chelator, XDPAdeCage to extract the Zn2+ from the blood serum and then release the chelated Zn2+ into a buffer using 365 nm light for quantification by an 8-17 DNAzyme sensor. Protocols to chelate, uncage, extract, and detect metal ions in the serum have been developed and optimized. Because DNAzyme sensors for other metal ions have already been reported and more DNAzyme sensors can be obtained using in vitro selection, the method reported in this work will significantly expand the applications of the DNAzyme sensors from sensing metal ions that are not only free but also bound to other biomolecules in biological and environmental samples.

Coordination Chemistry of a Controlled Burst of Zn2+ in Bulk Aqueous and Nanosized Water Droplets with a Zincon Chelator.

The light-induced photolysis of [Zn(NTAdeCage)]- generates a temporally controlled burst of Zn2+, which is rapidly chelated in situ by the free ligand Zincon2-. The [Zn(Zincon)]2- coordination progress is monitored using absorption spectroscopy in bulk aqueous buffer and reverse micelle environments. The [Zn(NTAdeCage)]- photocage and free ligand Zincon2- have different reverse micelle locations that affect the [Zn(Zincon)]2- formation at the nanoscale compared to the bulk aqueous buffer. The formation of [Zn(Zincon)]2- in a bulk aqueous buffer is more efficient despite the released Zn2+ and Zincon2- being physically closer within reverse micelles. The observed reduction of complex formation is attributed to the interfacial partitioning of Zincon2-, distinct from the Zn2+ photocage in the water pool, requiring diffusion for the species to meet to form [Zn(Zincon)]2-. This work introduces a proof-of-concept methodology to experimentally measure fast chelation reactions in confined spaces and thus provides an approach to exploring cellular responses.

On-demand guest release from MOF-5 sealed with nitrophenylacetic acid photocapping groups.

Recently, we demonstrated that triphenylacetic acid could be used to seal dye molecules within MOF-5, but guest release required the digestion of the framework by treatment with acid. We prepared the sterically bulky photocapping group [bis-(3-nitro-benzyl)-amino]-(3-nitro-phenyl)-acetic acid (PC1) that can prevent crystal violet dye diffusion from inside MOF-5 until removed by photolysis.

Catalytic Nanoassemblies Formed by Short Peptides Promote Highly Enantioselective Transfer Hydrogenation.

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).

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

Photocaged complexes can control the availability of metal ions to interrogate cellular signaling pathways. We describe a new photocage, {bis[(2-pyridyl)methyl]amino}(9-oxo-2-xanthenyl)acetic acid (XDPAdeCage, 1), which utilizes a 2-xanthone acetic acid group to mediate a photodecarboxylation reaction. XDPAdeCage photolyzes with a quantum yield of 27%, and binds Zn2+ with 4.6 pM affinity, which decreases by over 4 orders of magnitude after photolysis. For comparison to our previous approach to Zn2+ release via photodecarboxylation, the analogous photocage {bis[(2-pyridyl)methyl]amino}(m-nitrophenyl)acetic acid (DPAdeCage, 2), which uses a m-nitrobenzyl chromophore, was also prepared and characterized. The advantages of the 2-xanthone acetic acid chromophore include red-shifted excitation and a higher extinction coefficient at the preferred uncaging wavelength. The neutral ternary complex of [Zn(XDPAdeCage)]+ with the anionic ligand pyrithione is membrane permeable, which circumvents the need to utilize invasive techniques to introduce intracellular Zn2+ fluctuations. Using fluorescent imaging, we have confirmed transport of Zn2+ across membranes; in addition, RT-PCR experiments demonstrate changes in expression of Zn2+-responsive proteins after photolysis.

Emissive Azobenzenes Delivered on a Silver Coordination Polymer.

Azobenzene has become a ubiquitous component of functional molecules and polymeric materials because of the light-induced trans → cis isomerization of the diazene group. In contrast, there are very few applications utilizing azobenzene luminescence, since the excitation energy typically dissipates via nonradiative pathways. Inspired by our earlier studies with 2,2'-bis[ N,N'-(2-pyridyl)methyl]diaminoazobenzene (AzoAM oP) and related compounds, we investigated a series of five aminoazobenzene derivatives and their corresponding silver complexes. Four of the aminoazobenzene ligands, which exhibit no emission under ambient conditions, form silver coordination polymers that are luminescent at room temperature. AzoAE pP (2,2'-bis[ N,N'-(4-pyridyl)ethyl]diaminoazobenzene) assembles into a three-dimensional coordination polymer (AgAAE pP) that undergoes a reversible loss of emission upon the addition of metal-coordinating analytes such as pyridine. The switching behavior is consistent with the disassembly and reassembly of the coordination polymer driven by displacement of the aminoazobenzene ligands by coordinating analytes.

A Zinc(II) Photocage Based on a Decarboxylation Metal Ion Release Mechanism for Investigating Homeostasis and Biological Signaling.

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.

Increasing the dynamic range of metal ion affinity changes in Zn2+ photocages using multiple nitrobenzyl groups.

Two generations of DiCast photocages that exhibit light-induced decreases in metal ion affinity have been prepared and characterized. Expansion of the common Zn(2+) chelator of N,N-dipicolylaniline (DPA) to include additional aniline ligand provides N,N'-diphenyl-N,N'-bis(pyridin-2-ylmethyl)ethane-1,2-diamine, a tetradentate ligand that was functionalized with two photolabile groups to afford DiCast-1. Uncaging of the nitrobenzhydrol reduces the electron density on two metal-bound aniline ligands, which decreases the Zn(2+) affinity 190-fold. The analogous MonoCast photocage with a single nitrobenzhydrol group only undergoes a 14-fold reduction in affinity after an identical photochemical transformation. A second series of DiCast photocages based on a N,N'-(pyridine-2,6-diylbis(methylene))dianiline scaffold, which allows the introduction of two additional Zn(2+)-binding ligands into a preorganized chelator, expand on the multi-photolabile group strategy. DiCast-2 includes two pyridine ligands while DiCast-3 adds two carboxylate groups. Addition of bridging pyridine to the second generation photocages leads to more stable Zn(2+) complexes, and photolysis of two photolabile groups increases the Zn(2+) affinity changes to 480-fold. The Zn(2+), Cu(2+), and Cd(2+) binding properties were examined in all the DiCast photocages and the corresponding photoproducts using UV-vis spectroscopy. Further insight into the photocage Zn(2+)-binding motifs was obtained by X-ray analysis of DiCast-2 and DiCast-3 model ligands.

Differential sensing of Zn(II) and Cu(II) via two independent mechanisms.

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).

Zinc(II) mediated imine-enamine tautomerization.

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.

Site-selective imination of an anthracenone sensor: selective fluorescence detection of barium(II).

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.

Substitution of thiophene oligomers with macrocyclic end caps and the colorimetric detection of Hg(II).

Alkyl substitution at the α position(s) of mono-, bi-, and terthiophenes via electrophilic addition of macrocyclic end caps combines linear, π-conjugated aromatic compounds and annular macrocycles. Addition of the Hg(II) ion to terthiophene adducts produces intense color changes, allowing for the selective, colorimetric detection of mercury(II). Chemical oxidation of the asymmetric terthiophene adduct produces the sexithiophene oligomer.