Metal Ion Receptor Research Articles

Altered selectivity of a dipicolylamine based metal ion receptor

2,2-Dipicolylamine (DPA) based receptors detect Zn(2+) with high fidelity. A fluorescent sensor with thiocarbamate-linked DPA turns it into a highly selective module for Ag(+) with up to ~7-fold enhancement of fluorescence. The sensor exhibits a double ratiometric behavior. It also displays an interesting [Ag(+)] dependent aggregation induced emission.

Azacrown[N,S,O]-modified porphyrin sensor for detection of Ag+, Pb2+, and Cu2+

One new azacrown[N,S,O]-modified metal-free porphyrin derivative, H2Por-azacrown (1), with the central tetrapyrrole moiety as signaling fluorophore and/or metal ion receptor has been designed, synthesized, and characterized. Addition of Ag(+) into this novel metal-free porphyrin compound induces a fluorescence ON-OFF process, while adding Pb(2+) leads to absorption/emission-ratiometric signals. Quite interestingly, blue-shift of the Soret band, ratiometric change of Q bands, and dual-signal changes (absorption ratio and fluorescence ON-OFF) associated with the Cu(2+) displacement from the 1-Pb(2+) system were observed upon addition of Cu(2+). These results render this H2Por-azacrown compound a porphyrin-based multi-responsive optical sensor towards Ag(+), Pb(2+), and in particular Cu(2+) with dual-mode detecting potential.

Benzimidazole-based chromogenic chemosensor for the recognition of oxalic acid via counter ion displacement assay in semi-aqueous medium

An azo dye-coupled benzimidazole-based receptor 1 was synthesized and investigated as a receptor for metal ions in semi-aqueous medium. The receptor recognizes Cu2+ with high selectivity over other metal ions. The resultant complex 1·Cu2+ was found to selectively bind oxalic acid via counter ion displacement.

Integration of the 1,2,3‐Triazole “Click” Motif as a Potent Signalling Element in Metal Ion Responsive Fluorescent Probes

In a systematic approach we synthesized a new series of fluorescent probes incorporating donor-acceptor (D-A) substituted 1,2,3-triazoles as conjugative π-linkers between the alkali metal ion receptor N-phenylaza-[18]crown-6 and different fluorophoric groups with different electron-acceptor properties (4-naphthalimide, meso-phenyl-BODIPY and 9-anthracene) and investigated their performance in organic and aqueous environments (physiological conditions). In the charge-transfer (CT) type probes 1, 2 and 7, the fluorescence is almost completely quenched by intramolecular CT (ICT) processes involving charge-separated states. In the presence of Na(+) and K(+) ICT is interrupted, which resulted in a lighting-up of the fluorescence in acetonitrile. Among the investigated fluoroionophores, compound 7, which contains a 9-anthracenyl moiety as the electron-accepting fluorophore, is the only probe which retains light-up features in water and works as a highly K(+)/Na(+)-selective probe under simulated physiological conditions. Virtually decoupled BODIPY-based 6 and photoinduced electron transfer (PET) type probes 3-5, where the 10-substituted anthracen-9-yl fluorophores are connected to the 1,2,3-triazole through a methylene spacer, show strong ion-induced fluorescence enhancement in acetonitrile, but not under physiological conditions. Electrochemical studies and theoretical calculations were used to assess and support the underlying mechanisms for the new ICT and PET 1,2,3-triazole fluoroionophores.

Ion Interactions with a New Ditopic Naphthalimide‐Based Receptor: A Photophysical, NMR and Theoretical (DFT) Study

A new multi-component chemosensor system comprising a naphthalimide moiety as fluorophore is designed and developed to investigate receptor-analyte binding interactions in the presence of metal and non-metal ions. A dimethylamino moiety is utilized as receptor for metal ions and a thiourea receptor, having acidic protons, for binding anions. The system is characterized by conventional analytical methods. The absorption and fluorescence spectra of the system consist of a broad band typical for an intramolecular charge transfer (ICT). The effects of various metal-ion additives on the spectral behavior of the present sensor system are examined in acetonitrile. It is found that among the metal ions studied, alkali/alkaline earth-metal ions and transition-metal ions modulate the absorption and fluorescence spectra of the system. As an additional feature, the anion signaling behavior of the system in acetonitrile is studied. A decrease in fluorescence efficiency of the system is observed upon addition of fluoride and acetate anions. Fluorescence quenching is most effective in the case of fluoride ions. This is attributed to the enhancement of the photoinduced electron transfer from the anion receptor to the fluorophore moiety. Hydrogen-bond interactions between the acidic NH protons of the thiourea moiety and the F(-) anions are primarily attributed to the fluoride-selective signaling behavior. Interestingly, a negative cooperativity for the binding event is observed when the interactions of the system are studied in the presence of both Zn(2+) and F(-) ions. NMR spectroscopy and theoretical calculations are also carried out to better understand the receptor-analyte binding.

Coordination polymers of sodium 2-(quinolin-8-yloxy)propionate: A receptor for selective metal ions

Unusual bifurcated and trifurcated carboxylate binding to sodium ions in a one dimensional coordination polymer, [{Na2L(H2O)3}Br·H2O]n (1) (where L=2-(quinolin-8-yloxy)propionate), was observed. The ionic coordination polymer 1, possessing bromide anions, has sodium ions in two independent coordination environments. Reaction of 1 with perchloric acid led to anion exchange to form the dinuclear complex [Na2(HL)2(ClO4)2(μ-H2O)] (2). A cadmium coordination polymer [Cd(L)Br]n (3) was prepared by reacting 1 with cadmium(II) acetate. This one dimensional cadmium coordination polymer 3 has cadmium ions in a distorted square pyramidal geometry. The uniqueness of the cadmium polymer is that the bromide ions are inside the coordination sphere and it forms parallel sheet-like structures of polymeric chains through bromide–bromide interactions. The coordination polymer 1 and the dinuclear complex 2 are weakly fluorescent, whereas complex 3 is highly fluorescent. The coordination polymers 1 and 2 are fluorescence receptors for Mg, Ca, Ba, Zn, Cd and Hg in the (+2) oxidation state.

Zn2+ Binding‐Enabled Excited State Intramolecular Proton Transfer: A Step toward New Near‐Infrared Fluorescent Probes for Imaging Applications

In order to facilitate the in vivo study of zinc-related biology, it is essential to develop a zinc-selective sensor that exhibits both near-infrared (NIR) emission and larger Stokes shift. A fluorescent sensor, Zinhbo-5, has been constructed by using bis(benzoxazole) ligand with 2, 2'-dipicolylamine (DPA) as metal ion receptor. In aqueous solution, Zinhbo-5 exhibits high sensitivity (K(d) = 2.58 nM(2) ) and selectivity for Zn(2+) cation, revealing about 14-fold fluorescence enhancement upon zinc binding to give green emission. Remarkably, Zn(2+) binding to Zinhbo-5 switches on the excited state intramolecular proton transfer (ESIPT), producing the desirable near-infrared region (over 710 nm) with large Stokes shift (ca. 240 nm). The new probe is demonstrated to be useful for in vivo imaging of the intracellular Zn(2+) ion. The Zinhbo-5 is also useful for detecting zinc ion distribution during the development of living zebrafish embryos.

Synthesis and inclusion properties of C3-symmetric triazole derivatives based on hexahomotrioxacalix[3]arene

A series of metal ion receptors cone-7,15,23-tri-tert-butyl-25,26,27-tris{[1H-(1-arylmethyl)(1,2,3-triazolyl)]-4-methoxy}hexahomotrioxacalix[3]arenes, cone-3–cone-5, have been synthesized from 7,15,23-tri-tert-butyl-25,26,27-tris(propargyloxy)hexahomotrioxacalix[3]arene 2via click chemistry. The complexation properties of the receptors cone-3–cone-5 toward the selected binding of heavy metal and transition metal ions have been evaluated. The structure of cone-3 was elucidated by single-crystal X-ray crystallography.

Designed To Dissolve: Suppression of Colloidal Aggregation of Cu(I)-Selective Fluorescent Probes in Aqueous Buffer and In-Gel Detection of a Metallochaperone

Due to the lipophilicity of the metal-ion receptor, previously reported Cu(I)-selective fluorescent probes form colloidal aggregates, as revealed by dynamic light scattering. To address this problem, we have developed a hydrophilic triarylpyrazoline-based fluorescent probe, CTAP-2, that dissolves directly in water and shows a rapid, reversible, and highly selective 65-fold fluorescence turn-on response to Cu(I) in aqueous solution. CTAP-2 proved to be sufficiently sensitive for direct in-gel detection of Cu(I) bound to the metallochaperone Atox1, demonstrating the potential for cation-selective fluorescent probes to serve as tools in metalloproteomics for identifying proteins with readily accessible metal-binding sites.

Abstract 35: Genome-wide molecular profiling of peri-tumoral neocortex revealed genes possibly responsible for tumor-induced epilepsy

Abstract Epilepsy is a common cause of morbidity affecting approximately one third of patients with primary brain tumors. The molecular mechanism underlying the tumor induced epileptogenesis is poorly understood. Since the alteration in the peritumoral microenvironments is believed to play a significant role in inducing the epileptic state, we hypothesize that the change in gene expression of neighboring astrocytes and neurons may contribute to the increased neuronal excitability. To identify the genes possibly responsible for tumor induced epilepsy, a genome-wide gene expression profiling was conducted using Affymetrix HG U133 plus 2.0 arrays and RNAs derived from 1-5 year old formalin-fixed paraffin embedded (FFPE) peritumoral cortex from 5-paired (seizure vs. non-seizure) low grade brain tumor patients. RNAs were extracted from 3-5 microdisections of FFPE tissue blocks using Qiagen RNeasy FFPE kit and cDNA were synthesized and amplified using NuGen's WT-Ovation FFPE RNA amplification system and FL-Ovation cDNA biotin module. Our results showed that although FFPE derived RNAs were significant fragmented with a peak of 100-200 bases, gene detection rate was found to be significant high (up to 49.8%) with excellent 3’/5’ ratios (GAPDH, 1-3.4). The rate of gene detection is depending on the archive time of tissue blocks (correlation coefficient = -0.71, P< 0.05). We identified 345 differentially expressed genes (DEGs, 2-fold plus P < 0.05). Principal Component Analysis (PCA) based on both global genes and 345 DEGs showed that epilepsy samples were clustered together tightly (except one sample) and were clearly separated from the non-epilepsy samples. Gene Ontology (GO) analysis on 345 DEGs revealed several important functional groups of genes including signal transduction (20.6%), metal ion binding (18.2%), cation binding (17.9%), receptor activity (10.8%) and receptor binding (4.0%). Other significant DEGs include transcription factors, glutamate receptors and intercellular matrix proteins. Pathway analysis showed these 345 DEGs were mainly involved in focal adhesion (12 genes), ECM-receptor interaction (11 genes) and cell communication (9 genes) pathways. In conclusion, our study showed that (1) archival FFPE brain tissue is an excellent resource for genomic studying; and (2) the altered gene expression in the peri-tumoral neurons implicate multiple cellular pathways in the induction of the epileptic state. Identification of genes responsible for brain tumor-induced epilepsy may lead to novel and better management of epilepsy in brain tumor patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 35. doi:10.1158/1538-7445.AM2011-35

Discriminating octahedral transition metal ions: highly selective tripodal tris-(2,2′-bipyridine) functionalized piperazine cyclophane receptor for Cu2+ ions

New tripodal transition metal ion receptors, tris(5-ethoxycarbonyl-2,2'-bipyridine) and tris(5-carboxylate-2,2'-bipyridine) substituted 27-membered trimeric piperazine cyclophanes 5 and 7 as well as tetra(5-ethoxycarbonyl-2,2'-bipyridine) substituted 36-membered tetrameric piperazine cyclophane 6, have been prepared and their transition metal ion complexing properties studied in solution by UV-vis spectroscopy and in the solid state by single-crystal X-ray diffraction. The crystal structures of [H(3)5(3+)·Fe(2+)]·4(ClO(4)(-))·CF(3)COO(-) (V), [H(3)7(2+)·Fe(2+)]·2(SO(4)(2-)) (VII) and the reference complex [tris(5,5'-bis(ethoxycarbonyl)-2,2'-bipyridine)Fe(II) perchlorate] (I) showed that the robust piperazine cyclophane is an optimal platform in preorganizing the 2,2'-bipy moieties to form a very fixed octahedral coordination site. In an acidic water solution, the highly preorganized structure of 5 gives a [5·Fe(2+)] complex, the stability of which is comparable with the classical tris(2,2'-bipy) Fe(2+)-complex but it is a significant 3.7 logK units more stable than the non-preorganized tetrameric analog [6·Fe(2+)]. Detailed studies with other similar divalent octahedral transition metal cations showed that the restricted octahedral coordination in complexes of 5 results in an unusual selectivity. The selectivity order [Zn(2+)<Co(2+)<Ni(2+)≈Fe(2+)<Cu(2+)] deviates significantly from that of typical tris(2,2'-bipy) complexes [Zn(2+)<Co(2+)<Cu(2+)≈Fe(2+)<Ni(2+)]. As a highlight, cyclophane 5 exhibits exceptionally high selectivity towards Cu(2+) ions but very weak binding for Co(2+).

An efficient fluoroionophore for selective recognition of Hg 2+ and Cu 2+ ions

An azo-phenol based receptor 2 viz., 1-(6-nitrobenzothiazole-2-ylazo)naphthalene-2-ol has been designed, synthesized and characterized. The sensing behavior of receptor for different metal ions viz. Na +, K +, Ca 2+, Co 2+, Ni 2+, Cu 2+, Zn 2+, Hg 2+, Ag + and Cd 2+ has been studied in aqueous acetonitrile solution and was found specific for both the Hg 2+ and Cu 2+ transition metal ions. The chemosensor upon interaction with Hg 2+ and Cu 2+ ions shows well defined naked-eye visible color change from a yellow-green to pink and blue respectively, with a significant red-shift in absorption spectra. The estimated association constant and, enhancement and quenching in fluorescence emission spectra respectively, reveals the affinity of chemosensor for Hg 2+ and Cu 2+ ions. The FT-IR spectral analysis have suggested the probability of complexation, in the reaction medium, between metal ions and 2, through naphthol OH, azo N and thiazole N as a potential coordination sites.

Synthesis of new hydrazones based on tetrathiacalix[4]arene in the 1,3-alternate conformation

Reactions of 1,3-alternate stereoisomers of tetrathiacalix[4]arene and 4-tert-butyltetrathiacalix[4]-arene, functionalized by hydrazide groups, with benzaldehyde and pyridin-2-carbaldehyde gave new tetrathiacalix[ 4]arene tetrahydrazone derivatives as promising receptors for transition and toxic heavy metal ions.

Nickel(ii) and iron(iii) selective off-on-type fluorescence probes based on perylene tetracarboxylic diimide

Two novel "turn-on" fluorescent probes with perylene tetracarboxylic diimide (PDI) as the fluorophore and two different di-(2-picolyl)-amine (DPA) groups as the metal ion receptor (PDI-1 and PDI-2) were successfully synthesized with satisfactory yields. PDI-1 exhibited high selectivity toward Ni(2+) in the presence of various other metal cations including Zn(2+), Cd(2+) and Cu(2+) which were expected to interfere significantly. A 1 : 2 stoichiometry was found for the complex formed by PDI-1 and Ni(2+) by a Job's plot and by non-linear least square fitting of the fluorescence titration curves. By introducing an extra diamino ethylene group between DPA and the phenyl bridge, the receptor was modified and the high selectivity of the sensor toward Ni(2+) shifted to Fe(3+). The enhancement factor of the fluorescence response of PDI-2 to Fe(3+) was as high as 138. The binding behavior of the receptors in these two compounds is affected significantly by the PDI fluorophores. Most interestingly, both Ni(2+) and Fe(3+) are paramagnetic metal ions, which are known as fluorescence quenchers and are rarely targeted with "turn-on" fluorescence probes. This result suggests that PDIs are favorable fluorophores for a "turn-on" fluorescence probe for paramagnetic transition metal ions because of their high oxidation potential.

The role of metal ions and counterions in the switching behavior of a carboxylic acid functionalized spiropyran

The ability of a carboxylic acid functionalized spiropyran, SP, to act as a reversible and selective receptor for metal ions has been systematically examined. A series of spectroscopic measurements, combined with single-crystal X-ray diffraction have been employed in order to determine metal-ion sensitivity and selectivity, binding constants, solution compositions, binding kinetics as well as solid-state structure of a metal-complex of this ligand. This molecule acts as a chelating ligand and binds to metal ions using a triad of functionalities and will release the metal ion by application of visible light. Altering the complex from ZnCl(2) and Zn(ClO(4))(2), leads to only a small change in the complex absorption maxima from 494 to 492 nm, but produced a drastic increase in the sensitivity for the zinc(II) ion. Fluorescence spectroscopy was employed to establish that the detection limit for Zn(II) is approximately 3 x 10(-7) M for Zn(ClO(4))(2). The counterion also influences binding constants and the equilibrium constants for Cu(ClO(4))(2) and CuCl(2) are K = 3.37 x 10(4) M(-1) to K = 2.04 x 10(3) M(-1), respectively. Additionally, in the presence of perchlorate, the spiropyran-Cu complex formation is fast enough to allow for real-time naked eye detection of this metal ion in less than three minutes; the formation of other metal complexes takes between 50 minutes to 2 hours. Finally, the single-crystal structure determination of the SP-zinc chloride complex shows that the Zn(II) ion displays a distorted square-pyramidal arrangement, and neighbouring metal ions are bound together into a 1-D coordination polymer with a hydrophilic core, surrounded by hydrophobic 'cladding'.

Dithiocarbamate-Coated SERS Substrates: Sensitivity Gain by Partial Surface Passivation

The surface-enhanced Raman scattering (SERS) activity of nanoporous gold (NPG) can be boosted by controlled surface passivation. The SERS activities of unfunctionalized NPG were first optimized by etching substrates with NaI/I(2) (triiodide) and using 2-mercaptopyridine (2-MP) as the probing analyte. Gains in analyte sensitivity were then achieved by passivating the superficial regions of the NPG substrates with dimethyldithiocarbamate (Me(2)DTC) while leaving the more recessed "hot spots" available for SERS detection. Partial surface passivation with DTCs increased the substrate sensitivity to chemisorptive analytes such as 2-MP by an order of magnitude, whereas surface saturation lowered the sensitivity by an order of magnitude. The partially passivated NPG films can also be functionalized with supramolecular receptors for chemoselective SERS. Installation of a DTC-anchored terpyridine enabled the detection of divalent metal ions at trace levels, as determined by the complexation-induced shift of a characteristic Raman peak of the metal ion receptor.

Synthesis and structural characterization of 18-, 19-, 20- and 22-membered Schiff base macrocycles

Six new dioxadiaza macrocyclic Schiff bases with 18-, 19-, 20- and 22-membered rings have been synthesized from diamine and dialdehyde building blocks. An X-ray diffraction study and molecular modelling (at the HF/6-31G(d,p) level of theory) have been performed to determine their molecular geometries and structural configurations. According to the theoretical studies the most stable conformers of the macrocycles are those, in which the lone pair electrons localized on the nitrogen atoms are exo-oriented, and those on the oxygen atoms are endo-oriented with respect to the cavity. In order to obtain more proper metal ion receptors with all lone pair electrons directed into the cavity, two Schiff base macrocycles have been reduced to the corresponding diamines, of which one could be isolated only as a very stable oxaazacyclophane borane adduct. Six dioxadiaza macrocyclic Schiff bases with 18-, 19-, 20- and 22-membered rings were synthesized and their molecular geometries and structural configurations were determined by X-ray diffraction and molecular modelling. In addition, two of these macrocycles were reduced to the corresponding diamines, of which one could be isolated only as a very stable oxaazacyclophane borane adduct.

Novel heavy-metal adsorption material: ion-recognition P(NIPAM-co-BCAm) hydrogels for removal of lead(II) ions

A novel polymeric lead(II) adsorbent is prepared by incorporating benzo-18-crown-6-acrylamide (BCAm) as metal ion receptor into the thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel. Both stimuli-sensitive properties and the Pb(2+)-adsorption capabilities of the prepared P(NIPAM-co-BCAm) hydrogels are investigated. The prepared P(NIPAM-co-BCAm) hydrogels exhibit good ion-recognition and Pb(2+)-adsorption characteristics. When crown ether units capture Pb(2+) and form BCAm/Pb(2+) host-guest complexes, the lower critical solution temperature (LCST) of the hydrogel shifts to a higher temperature due to both the repulsion among charged BCAm/Pb(2+) groups and the osmotic pressure within the hydrogel. The adsorption results at different temperatures show that P(NIPAM-co-BCAm) hydrogels adsorb Pb(2+) ions at temperature lower than the LCST, but undergo desorption at temperature higher than the LCST due to the "stretch-to-shrink" configuration change of copolymer networks which is triggered by the change in environmental temperature. This kind of ion-recognition hydrogel is promising as a novel adsorption material for adsorption and separation of Pb(2+) ions. The adsorption and desorption of Pb(2+) could be rationally achieved by simply changing the environmental temperature.

Synthesis and characterization of linear molecular assembly of crystalline calix[4]arenes dithianes

A family of six new variously substituted calix[4]arene dithianes has been prepared from respective formyl and acetyl derivatives. Shorter reaction time, mild conditions, and facile isolation of desired products are attractive features of the described method. The new 1,2-dithiane derivatives have been characterized by 1H NMR, 13C NMR spectroscopy, and FABMS analysis. The crystal structure of one of the acetyl calix[4]arene dithiane was determined by X-ray diffraction analysis, which revealed a dithiane capped linear molecular organization. Preliminary evaluation of bis (dithiane) calix[4]arene derivatives as molecular receptor for transition metal ions has revealed strong interaction with Hg 2+ in 1:1 stoichiometry.

Selective heavy metal receptor functional phthalocyanines bearing thiophenes: Synthesis, characterization, spectroscopy and electrochemistry

Soft metal ion receptor 2,9,16,23-tetrakis-6-(-thiophene-2-carboxylate)-hexylthio-phthlocyaninato zinc(II) and cobalt(II) complexes derived from 6-(3,4-dicyanophenylthio) hexylthiophene-2-carboxylate have been prepared as an isomeric mixture via cyclotetramerization reactions. The complexes have been fully characterized by elemental analysis, FTIR, 1H and 13C NMR, MS (ESI and MALDI-TOF) and by UV–vis spectral data. Soft metal ion binding ability of the complexes with Ag I, Pd II, Hg II and Cd II has been evaluated by UV–vis spectroscopic titration technique. Cyclic and differential pulse voltammetries show that while Zn(II)Pc gives up to two ligand-based reduction and one ligand-based oxidation processes having diffusion-controlled reversible electron transfer properties, Co(II)Pc represents one ligand-based and one metal-based oxidation and one metal-based and one ligand-based reduction processes having diffusion-controlled reversible electron transfer characters. Assignments of the redox couples of Co(II)Pc are confirmed by spectroelectrochemical measurements.