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+ .

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.

Following the Ca²âº roadmap to photocaged complexes for Zn²âº and beyond.

The first photocaged complexes appeared in the mid-1980s specifically to complement the ongoing work studying intracellular Ca(2+) signaling with fluorescent probes. Recently, the field of biological inorganic chemistry has focused increasingly on the homeostasis mechanisms and possible signaling functions of transition metal ions like Mn(2+), Fe(2+), Cu(+) and Zn(2+). Development of fluorescent sensors for imaging studies has been a very active area of research; however the corresponding chemical tools for delivering metal ions have received less interest. Using the roadmap provided by Ca(2+) predecessors, we describe how new photocaged complexes are being developed, and highlight some of the obstacles that must be overcome to investigate an emerging area in metal ion biology with different requirements.

Quantifying factors that influence metal ion release in photocaged complexes using ZinCast derivatives.

Two generations of nitrobenzhydrol-based photocages for Zn(2+) have been prepared and characterized. The first series includes the tridentate ZinCast-1 utilizes a bis-pyridin-2-ylmethyl-aniline ligand that forms a 5,5-chelate ring upon metal binding. The related photocages ZinCast-2 with a N-[2-(pyridine-2-yl)ethyl]-N-(pyridine-2-ylmethyl)aniline (5,6-chelate ring) and ZinCast-3 with a N,N-bis[2-(pyridine-2-yl)ethyl]aniline (6,6-chelate ring) were synthesized for comparative studies. The complexes formed by the ions Cu(2+), Zn(2+) and Cd(2+) with three ZinCast and their photoproducts (ZinUnc) were interrogated by UV-Vis spectroscopy. The studies indicate that ZinCast-1 forms complexes of the highest stability and ZinCast-3 exhibits the most significant changes in metal affinity upon uncaging. These results suggest that the changes in nitrogen atom donor ability as well as the initial complex stability must be considered to design a photocage with the desired properties. The composite results were used to design ZinCast-4 and ZinCast-5, the second generation photocages that incorporate an additional adjacent ether ligand into the Zn(2+) chelator.

ZinCast-1: a photochemically active chelator for Zn(2+).

Two strategies were applied to the synthesis of ZinCast-1, a nitrobenzhydrol-based caged complex that upon photolysis exhibits a nearly 400-fold difference in binding for Zn(2+).

Methods for preparing metal ion photocages: application to the synthesis of crowncast.

Three different synthetic strategies were utilized in the construction of a novel class of macrocyclic containing o-nitrobenzhydrol group II cation cages. The synthetic methodology presented herein is unparalleled in scope toward the preparation of caged complexes for various main group and transition block cations.