Relevant Metal Ions Research Articles

Synthesis, Complexation and DFT Computational Studies of Bis(naphthyl)methane‐“Capped” Triazole‐Linked Calix[4]arenes as Fe3+ Fluorescent Chemosensors

AbstractTwo new substituted‐bis(naphthyl)methane “capped” 1,2,3‐triazole‐linked calix[4]arene receptors have been synthesized and characterized. Their binding properties toward different biologically relevant metal ions were studied by fluorescence spectroscopy titrations and 1H NMR spectroscopy. The fluorescence spectral changes show that are sensitive and selective for Fe3+ ions and the binding modes have been confirmed based upon both the 1H NMR and DFT studies.

An Aptamer-based Sensor for Unchelated Gadolinium(III)

A method for determining the presence of unchelated trivalent gadolinium ion (Gd3+) in aqueous solution is demonstrated. Gd3+ is often present in samples of gadolinium-based contrast agents as a result of incomplete reactions between the ligand and the ion, or as a dissociation product. Since the ion is toxic, its detection is of critical importance. Herein, the design and usage of an aptamer-based sensor (Gd-sensor) for Gd3+ are described. The sensor produces a fluorescence change in response to increasing concentrations of the ion, and has a limit of detection in the nanomolar range (~100 nM with a signal-to-noise ratio of 3). The assay may be run in an aqueous buffer at ambient pH (~7 - 7.4) in a 384-well microplate. The sensor is relatively unreactive toward other physiologically relevant metal ions such as sodium, potassium, and calcium ions, although it is not specific for Gd3+ over other trivalent lanthanides such as europium(III) and terbium(III). Nevertheless, the lanthanides are not commonly found in contrast agents or the biological systems, and the sensor may therefore be used to selectively determine unchelated Gd3+ in aqueous conditions.

An Aptamer-based Sensor for Unchelated Gadolinium(III).

A method for determining the presence of unchelated trivalent gadolinium ion (Gd3+) in aqueous solution is demonstrated. Gd3+ is often present in samples of gadolinium-based contrast agents as a result of incomplete reactions between the ligand and the ion, or as a dissociation product. Since the ion is toxic, its detection is of critical importance. Herein, the design and usage of an aptamer-based sensor (Gd-sensor) for Gd3+ are described. The sensor produces a fluorescence change in response to increasing concentrations of the ion, and has a limit of detection in the nanomolar range (~100 nM with a signal-to-noise ratio of 3). The assay may be run in an aqueous buffer at ambient pH (~7 - 7.4) in a 384-well microplate. The sensor is relatively unreactive toward other physiologically relevant metal ions such as sodium, potassium, and calcium ions, although it is not specific for Gd3+ over other trivalent lanthanides such as europium(III) and terbium(III). Nevertheless, the lanthanides are not commonly found in contrast agents or the biological systems, and the sensor may therefore be used to selectively determine unchelated Gd3+ in aqueous conditions.

Dual signaling of hypochlorite in tap water by selective oxidation of phenylselenylated dichlorofluorescein

A novel hypochlorite-selective signaling probe based on the oxidative transformation of phenylselenylated 2′,7′-dichlorofluorescein 1 to its selenoxide analogue was investigated. In a pH 7.0 phosphate buffer system (containing 1% DMF as a solubilizer), the designed probe 1 exhibited pronounced colorimetric and fluorogenic hypochlorite signaling behavior over other representative oxidants such as hydrogen peroxide, tert-butyl hydroperoxide, perborate, and percarbonate as well as a range of environmentally relevant metal ions and anions. The signaling was due to the hypochlorite-assisted oxidation of the probe’s selenyl moiety to selenoxide. Hypochlorite signaling was unaffected by the presence of common metal ions and anions as a background. The hypochlorite-selective fluorescence signaling of probe 1 has a detection limit of 3.9×10−8M (0.002ppm). Finally, the determination of hypochlorite concentration in tap water using a smartphone as a stand-alone portable signaling detection and processing tool was successfully demonstrated.

Colorimetric determination of Cu2+ in simulated wastewater using naphthalimide-based Schiff base

A new Cu2+-selective colorimetric sensor was developed by combining the chromophore 3-hydroxynaphthalimide with diaminomaleonitrile. The sensor showed Cu2+-selective colorimetric signaling behavior in dimethylsulfoxide, indicated by a solution color change from yellow to pink, which was readily discernible without any external devices. Practical application of the sensor to the detection of Cu2+ in an aqueous solution containing other environmentally relevant metal ions by selective two-phase liquid-liquid extraction with ethyl acetate was possible. Particularly, extractive signaling of Cu2+ in simulated semiconductor wastewater with a readily-usable smartphone as a colorimetric data capture and analysis tool was successfully conducted.

Benzodifuran Derivatives as Potential Antiproliferative Agents: Possible Correlation between Their Bioactivity and Aggregation Properties.

To further explore the properties and bioactivity of benzodifurans, three compounds in this class were synthesised and characterised using spectroscopic and spectrometric techniques, as well as SEM and thermogravimetric analysis. The synthesised compounds showed interesting antiproliferative activity on different human cancer cells (HeLa, Hep-G2, WM266), whereas no relevant cytotoxic effect was observed on healthy control cells. To study the possible mechanism of action of the benzodifurans, their ability to bind various model DNA systems, their aggregation properties, and their ability to bind biologically relevant metal ions was evaluated. The molecules were found to form monodisperse nanoaggregates stable at physiological temperature, which are likely related to the observed bioactivity.

Highly sensitive and selective “turn-on” chemodosimeter based on Cu2+- promoted hydrolysis for nanomolar detection of Cu2+ and its application in confocal cell imaging

Abstract Based on Cu2+- promoted hydrolysis reaction a rhodamine B derivative L containing a napthalene moiety has been synthesized as a fluorescence turn-on chemodosimetric probe for Cu2+ in EtOH:H2O (3:1, v/v, 10 mM HEPES Buffer, pH ≈ 7). The Cu2+ promoted ring opening and hydrolysis reaction of L leads to formation of the 2:1 ligand metal intermediate complex which rapidly converts to rhodamine-B and bis-Cu2+ complex of 1, 8 diaminonaphthalene. The proposed sensing mechanism has been supported by ESI–MS, 1H NMR, 13C NMR, IR analysis and DFT calculations. The dye L exhibits high selectivity toward Cu2+ over other relevant metal ions and anions in the physiological pH range 5–8 with a low detection limit of 60 nM. Application in confocal cell imaging in HeLa cells is also demonstrated in the current work. Additionally, L has been shown to be non-toxic and biocompatible for mammalian cells.

Transient Proteotoxicity of Bacterial Virulence Factor Pyocyanin in Renal Tubular Epithelial Cells Induces ER-Related Vacuolation and Can Be Efficiently Modulated by Iron Chelators.

Persistent infections of biofilm forming bacteria, such as Pseudomonas aeruginosa, are common among human populations, due to the bacterial resistance to antibiotics and other adaptation strategies, including release of cytotoxic virulent factors such as pigment pyocyanin (PCN). Urinary tract infections harbor P. aeruginosa strains characterized by the highest PCN-producing capacity, yet no information is available on PCN cytotoxicity mechanism in kidney. We report here that renal tubular epithelial cell (RTEC) line NRK-52E responds to PCN treatments with paraptosis-like activity features. Specifically, PCN-treated cells experienced dilation of endoplasmic reticulum (ER) and an extensive development of ER-derived vacuoles after about 8 h. This process was accompanied with hyper-activation of proteotoxic stress-inducible transcription factors Nrf2, ATF6, and HSF-1. The cells could be rescued by withdrawal of PCN from the culture media before the vacuoles burst and cells die of non-programmed necrosis after about 24-30 h. The paraptosis-like activity was abrogated by co-treatment of the cells with metal-chelating antioxidants. A microscopic examination of cells co-treated with PCN and agents aiming at a variety of the cellular stress mediators and pathways have identified iron as a single most significant co-factor of the PCN cytotoxicity in the RTECs. Among biologically relevant metal ions, low micromolar Fe2+ specifically mediated anaerobic oxidation of glutathione by PCN, but catechol derivatives and other strong iron complexing agents could inhibit the reaction. Our data suggest that iron chelation could be considered as a supplementary treatment in the PCN-positive infections.

Triazole-Linked Quinoline Conjugate of Glucopyranose: Selectivity Comparison among Zn2+, Cd2+, and Hg2+ Based on Spectroscopy, Thermodynamics, and Microscopy, and Reversible Sensing of Zn2+ and the Structure of the Complex Using DFT.

A water-soluble triazole-linked quinoline conjugate of glucopyranose (L) has been synthesized and characterized, and its single-crystal X-ray diffraction (XRD) structure has been established. Binding of L toward different biologically relevant metal ions has been studied using fluorescence and absorption spectroscopy in HEPES buffer at pH 7.4. The conjugate L detects Zn2+ and Cd2+ with 30 ± 2 and 14 ± 1-fold fluorescence enhancement, respectively, but in the case of Hg2+, only a fluorescence quench was observed. The stoichiometry of the complex is 1:2 metal ion to the ligand in the case of Zn2+ and Cd2+ resulting in [Zn(L)2] and [Cd(L)2], and it is 1:1 in the case of Hg2+, as confirmed from their electrospray ionization mass spectrometry (ESIMS) spectra. Zn2+ shows greater exothermicity over Cd2+, whereas Hg2+ shows endothermicity , which supports the differences in their binding strength and the nature of the corresponding complex. L exhibits rod-shaped particles and upon complexation with Zn2+, it exhibits sphere-like morphological features in scanning electron microscopy (SEM) images. However, clustered aggregates are observed in Cd2+, whereas the [HgL] complex exhibits small fused spherical structures, and therefore the signature of these ions is seen in microscopy images. The computational studies revealed that the syn-[Zn(L)2] complex is stabilized by 9.7 kcal mol–1 more than that in the case of anti-[Zn(L)2] owing to the formation of hydrogen bonds between the two glucosyl moieties within the syn-complex. Among the anions studied, [Zn(L)2] is sensitive and selective toward the phosphate ion (H2PO4–) with a minimum detection limit of 16 ± 2 ppb. Similarly, the [HgL] can act as a secondary sensor for CN– while also exhibiting reversibility. Based on the input–output characteristics, INHIBIT logic gate was built in the case of Zn2+ vs H2PO4– and IMPLICATION logic gate was built in the case of Hg2+ vs CN–.

A new fluorescent chemosensor for recognition of Hg2+ ions based on a coumarin derivative

A novel coumarin derivatives based fluorescent chemosensor CBH was designed and synthesized by Schiff base reaction, which was connected by 7-(N,N-diethylamino) coumarin-3-aldehyde and 3-methyl-2-benzothiazolinone hydrazone through C=N. X-ray single crystal structure analysis indicated that two aromatic groups of the CBH were almost in the same plane. It displayed enhancement of the fluorescent intensity and absorbance when the sensor CBH interacted with Hg2+ ions. The chemosensor CBH exhibited a good sensitive and selective recognition towards Hg2+ ions in the presence of other important relevant metal ions.

Selective Hg2+ signaling via dithiane to aldehyde conversion of an ESIPT fluorophore

We herein report the development of a simple structured reaction-based probe for the fluorescence signaling of Hg2+ ions using a dithiane derivative of an excited-state intramolecular proton transfer (ESIPT) dye. The designed probe exhibited prominent fluorescence signaling behavior towards Hg2+ ions by the deprotection of its dithiane function to an aldehyde in an aqueous acetonitrile solution. The interfering response of Cu2+ ions was efficiently removed using citrate as both a masking agent and a buffer. Thus, the use of a citrate buffer allowed exclusive Hg2+-selective signaling to be obtained in the presence of common environmentally relevant transition metal ions. Signaling of the Hg2+ ions was complete within 15 min after sample preparation, and a detection limit of 2.0 × 10−7 M was estimated. As a practical application of the designed probe, the detection of Hg2+ ions in simulated wastewater was tested using a smartphone as a portable signal-capturing device.

Metal Cations in G-Quadruplex Folding and Stability.

This review is focused on the structural and physicochemical aspects of metal cation coordination to G-Quadruplexes (GQ) and their effects on GQ stability and conformation. G-quadruplex structures are non-canonical secondary structures formed by both DNA and RNA. G-quadruplexes regulate a wide range of important biochemical processes. Besides the sequence requirements, the coordination of monovalent cations in the GQ is essential for its formation and determines the stability and polymorphism of GQ structures. The nature, location, and dynamics of the cation coordination and their impact on the overall GQ stability are dependent on several factors such as the ionic radii, hydration energy, and the bonding strength to the O6 of guanines. The intracellular monovalent cation concentration and the localized ion concentrations determine the formation of GQs and can potentially dictate their regulatory roles. A wide range of biochemical and biophysical studies on an array of GQ enabling sequences have generated at a minimum the knowledge base that allows us to often predict the stability of GQs in the presence of the physiologically relevant metal ions, however, prediction of conformation of such GQs is still out of the realm.

Transient Proteotoxicity of Bacterial Virulence Factor Pyocyanin in Renal Tubular Epithelial Cells Induces ER-Related Vacuolation and Can Be Efficiently Modulated by Iron Chelators.

Persistent infections of biofilm forming bacteria, such as Pseudomonas aeruginosa, are common among human populations, due to the bacterial resistance to antibiotics and other adaptation strategies, including release of cytotoxic virulent factors such as pigment pyocyanin (PCN). Urinary tract infections harbor P. aeruginosa strains characterized by the highest PCN-producing capacity, yet no information is available on PCN cytotoxicity mechanism in kidney. We report here that renal tubular epithelial cell (RTEC) line NRK-52E responds to PCN treatments with paraptosis-like activity features. Specifically, PCN-treated cells experienced dilation of endoplasmic reticulum (ER) and an extensive development of ER-derived vacuoles after about 8 h. This process was accompanied with hyper-activation of proteotoxic stress-inducible transcription factors Nrf2, ATF6, and HSF-1. The cells could be rescued by withdrawal of PCN from the culture media before the vacuoles burst and cells die of non-programmed necrosis after about 24–30 h. The paraptosis-like activity was abrogated by co-treatment of the cells with metal-chelating antioxidants. A microscopic examination of cells co-treated with PCN and agents aiming at a variety of the cellular stress mediators and pathways have identified iron as a single most significant co-factor of the PCN cytotoxicity in the RTECs. Among biologically relevant metal ions, low micromolar Fe2+ specifically mediated anaerobic oxidation of glutathione by PCN, but catechol derivatives and other strong iron complexing agents could inhibit the reaction. Our data suggest that iron chelation could be considered as a supplementary treatment in the PCN-positive infections.

Naked-eye detection of copper(II) ions by a “clickable” fluorescent sensor

A novel “clickable” sensing platform for signal-on fluorescent detection of Cu2+ has been developed based on the high regioselectivity of Cu(I)-catalyzed azide–alkyne click reaction (CuAAC) and the aggregated AIE-active molecules (BATPE) as the signal reporters. The CuAAC reaction causes a structural change of BATPE from molecularly dispersed to aggregate state in the presence of trace Cu2+, thus inducing a dramatic fluorescence “turn-on” response which can be judged with the naked eye. Under the optimum conditions, down to 0.2μM and 0.5μM Cu2+ were successfully detected by fluorescence spectrophotometer and naked eye, respectively. This method is simple and low-cost without the need for expensive equipment. Thanks to the superior specificity of CuAAC reaction, our assay is capable of sensing Cu2+ in the existence of other environmentally relevant metal ions in real samples, indicating that it may serve as a promising sensor for on-site Cu2+ analysis.

Fluorescent imaging of Au3+ in living cells with two new high selective Au3+ probes

Two new acetylenic compounds were designed and synthesized as the probes to realize the detection and recognition of Au(3+). The latent fluorophores was rearranged into the fluorescent coumarin derivatives with strong fluorescence by a gold ion-mediated hydroarylation reaction. In the meanwhile, the generated fluorescent substances were also isolated and characterized. The probes identified Au(3+) ions highly selectively over other biologically relevant metal ions, and detection concentration of Au(3+) was as low as 0.1µM or less. Fluorescent imaging of Au(3+) in living cells was also successfully demonstrated.

A Fluorescent Sensor for Al(III) and Colorimetric Sensor for Fe(III) and Fe(II) Based on a Novel 8-Hydroxyquinoline Derivative.

A novel 8-hydroxyquinoline-based fluorescent and colorimetric chemosensor was designed, synthesized and fully characterized. The sensor showed high selectivity and sensitivity toward Al(3+) over other tested cations in EtOH/H2O (1:99, v/v) medium. The increase in fluorescence intensity was linearly proportional to the concentration of Al(3+) with a detection limit of 7.38×10(-6)M. Moreover, the sensor exhibited an obvious color change from yellow to black in the presence of Fe(2+) and Fe(3+) in EtOH/THF (99:1, v/v) solution. The absorbance changes showed a linear response to iron ions with the detection limits of 4.24×10(-7)M and 5.60×10(-7)M for Fe(2+) and Fe(3+), respectively. Thus, this chemosensor provides a novel approach for selectively recognition of Al(3+), Fe(3+) and Fe(2+) among environmentally relevant metal ions.

A highly selective and sensitive “Turn-On” fluorescence chemosensor for the Cu 2+ ion in aqueous ethanolic medium and its application in live cell imaging

Abstract A new rhodamine 6G derived chemosensor L has been synthesized that selectively detects the presence of Cu 2+ ion over a host of other biologically important and environmentally relevant metal ions in aqueous alcoholic medium under physiological pH (ethanol: water, 1:1, v/v, pH 7.2). The significant enhancement of fluorescence intensity of L is caused by Cu 2+ ion induced cleavage of spirolactum bond in the rhodamine moiety. This mechanism is well supported by the crystal structure of the L-Cu 2+ complex that depicts two ligand units are bonded to two Cu 2+ ions. Color of the solution changes from light orange to dark pink upon metal binding which allows naked eye detection ion as well. Confocal microscopic experiments validate that the dye is potentially useful for the selective detection of Cu 2+ ion in living cells. Therefore the dye is an excellent fluorogenic and chromogenic chemosensor for the Cu 2+ ion in aqueous ethanolic medium and the living cell as well.

Synthesis and protein binding properties of novel highly functionalized Calix[4]arene

A novel protein binding agent based on highly functionalized calix[4]arene 5 has been synthesized and its structure characterized by 1H and 13C NMR, FT-IR and HRMS spectral data. Protein binding studies carried out using fluorescence spectroscopic technique revealed that this compound could bind strongly to lysozyme. Furthermore, the effect of compound 5 on the conformation of lysozyme was investigated using three-dimensional fluorescence spectroscopy. Finally, the influence of various biological relevant metal ions on the binding constant of lysozyme with 5 was studied.

A TBET based BODIPY-rhodamine dyad for the ratiometric detection of trivalent metal ions and its application in live cell imaging

A novel fluorescent BODIPY-rhodamine dyad probe that operates based on through bond energy transfer (TBET) phenomenon has been synthesized and its application in the detection of biologically relevant metal ions is explored. Among several metal ions, the probe selectively responds to the addition of trivalent metal ions (Al3+, Cr3+ and Fe3+) through its signature absorbance and fluorescence characteristics and permits their ratiometric detection. The trivalent metal ion detection ability of the probe is unaffected with the presence of other commonly coexistent ions. The probe is highly sensitive and it can detect the trivalent metal ions even at ppb level concentrations. The probe is nontoxic under the experimental conditions, cell permeable and useful for the imaging of Al3+, Cr3+ and Fe3+ ions present in W138 (normal lung fibroblast) cells.

Red to brown to green colorimetric detection of Ag+ based on the formation of Au-Ag core-shell NPs stabilized by a multi-sulfhydryl functionalized hyperbranched polymer

The hyperbranched polyethylenimine (HPEI) derivative with thiol (SH) terminals was synthesized and used as multidentate ligand to stabilize AuNPs/analyte composites. A facile and rapid colorimetric method for the sensitive and selective detection of Ag+ based on the formation of Au-Ag core-shell NPs with three color changes (red through brown to green) was developed. Successive multiple color changes can greatly improve the specificity and selectivity of this colorimetric sensor owing to the lower possibility of false positive results. Other environmentally relevant metal ions did not interfere with the determination of Ag+. The response (i.e., the absorbance at 600nm, A600nm) was linearly proportional to the Ag+ concentration in a range from 8.76×10−9 to 1.27×10−4M with a detection limit of 8.76×10−8M by the naked eyes and 8.76×10−9M by the UV–vis spectra. For the first time, this novel colorimetric sensor based on multiple color changes was developed and successfully applied to detect Ag+ in real samples.