Relevant Metal Ions Research Articles

Synthesis and Structural Analysis of 1,4,7,10‐Tetraazacyclododecane‐1,4,7,10‐­tetraazidoethylacetic Acid (DOTAZA) Complexes

AbstractHerein, we present the synthesis and structural analysis of metal complexes of enantiomerically pure 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraazidoethylacetic acid (DOTAZA). DOTAZA is a new tunable analog of DOTA, a clinically approved chelator for various pharmaceutically relevant metal ions. In this work, we investigate the complexation chemistry of DOTAZA and report the crystal structures of a number of complexes with pharmaceutically relevant metal ions such as Gd3+ [magnetic resonance imaging (MRI)], Eu3+ (luminescence spectroscopy), Y3+ [positron emission tomography (PET)], In3+ [single‐photon‐emission computed tomography (SPECT)], and Na+. These structures provide useful information for imaging applications and demonstrate the potential of DOTAZA to form stable complexes. Owing to its clickable azide functionalities, it may be used for the development of tailored imaging reagents that retain the positive complexation chemistry of the parent compound DOTA.

A highly selective and sensitive turn-on fluorescence chemosensor based on a rhodamine–adenine conjugate for Al3+ in aqueous medium: Bioimaging and DFT studies

Recently, extraordinary progress has been made for the specific detection of environmentally and biologically relevant metal ions in aqueous solution and living cells. A new dye L where rhodamine B is covalently attached to adenine has been synthesized in good yields. This dye is found to be highly specific in detecting of Al3+ ion in presence of excess of biologically relevant metal ions in DMSO/H2O [1:4 (v/v), HEPES buffer, pH=7.1] medium. Upon complexation with Al3+ the dye exhibits a substantially enhanced absorbance intensity at 566nm and fluorescence intensity at 590nm. Besides showing high selectivity, the sensor gives a sensitivity of 0.19µM for Al3+ in both absorbance and fluorescence studies over a wide pH range. The sensitivity is much higher compared to the value mentioned in the guidelines of WHO (7.41µM). Moreover, the dye shows moderately cytotoxicity and can be employed for the detection of intracellular concentration of Al3+ ions in living cells.

A rhodamine scaffold immobilized onto mesoporous silica as a fluorescent probe for the detection of Fe (III) and applications in bio-imaging and microfluidic chips

A novel ethylenediamine derivative of a rhodamine 6G silica particle (RSSP) was covalently grafted onto the surface of mesoporous silica to create a fluorescent chemosensing hybrid material for the detection of Fe3+. The prepared RSSP was dispersed in water, and its optical sensing response to various metal cations (Ag+, Na+, Li+, K+, Cs+, Hg2+, Cu2+, Ca2+, Cd2+, Co2+, Fe2+, Mg2+, Ni2+, Pb2+, Zn2+, Fe3+ and Al3+) was evaluated through the resulting fluorescence spectra. Upon coordination with Fe3+, the promoted ring opening of the rhodamine spirolactam ring in the RSSP activated a fluorescence response via CHEF (chelation enhancement fluorescence). This fluorescence enhancement was induced by the spirolactam ring system of the chemosensor immobilized in the pore. Conversely, the fluorescence response of the RSSP–Fe3+ complex was quenched by the addition of EDTA, which abstracted the Fe3+ ion from the complex and turned the sensor off, confirming that the recognition process was reversible. The proposed chemosensor also exhibited excellent selectivity for Fe3+ over competing environmentally relevant metal ions. The chemosensor can also be used over a wide pH range and was readily regenerated. The sensing ability of RSSP makes it desirable for practical applications in microfluidics analysis tools, intracellular bio-imaging and lab-on-a-chip development.

Role of diluents in the comparative extraction of Th(IV), U(VI) and other relevant metal ions by DHOA and TBP from nitric acid media and simulated wastes: Reprocessing of U–Th based fuel in perspective

Keeping reprocessing of 233U–Th based fuel in perspective, solvent extraction of Th(IV), U(VI) and some relevant metal ions has been carried out from nitric acid media and simulated high-level waste (HLW) typical of a fast-breeder reactor using dihexyloctanamide (DHOA) in commercially available alternate diluents, viz. Solvesso 100 and ShellSol D70. Acid uptake constant (KH) and distribution ratios (D) of metal ions as a function of nitric acid, thorium ion and extractant concentrations are determined. Slope-analysis results showed various types of species extracted into the organic phase. For comparison, a similar set of experiments were carried out with tri-n-butyl phosphate (TBP) in both diluents. A few clear and interesting trends were observed in the variation of D values of metal ions. Interference of other relevant metal ions likely to get co-extracted along with Th(IV) and U(VI) was also studied by ICP-AES using a simulated HLW.

Azomethine-H as a highly selective fluorescent probe for Fe3+ detection in 100% aqueous solution and its application in living cell imaging

A simple assay for the detection of Fe3+ in water by means of fluorescence spectroscopy was developed based on a commercially available reagent, Azomethine-H(A-H), allowing sensing trace levels of Fe3+ with high selectivity over other cations. A significant fluorescence quenching of A-H at 424 nm was found after its binding with Fe3+ in 100% aqueous solution at pH=7.0, while other physiologically relevant metal ions posed little interference. The fluorescence responses can be well described by the modified Stern-Volmer equation. A good linear relationship(R2=0.9904) was observed up to 1.6×10–5 mol/L Fe3+ ions. The detection limit, calculated via the 3σ IUPAC(international union of pure and applied chemistry) criteria, was 1.95×10–7 mol/L. Moreover, the colorimetric and fluorescent response of A-H to Fe3+ can be conveniently detected by the naked eye, providing a facile method for visual detection of Fe3+. The proposed method was used to determine Fe3+ in water samples. Moreover, inverted fluorescence microscopy imaging using human umbilical vein endothelial cells shows that A-H can be used as an effective fluorescent probe for detecting Fe3+ in living cells.

Colorimetric detection of Cu2+ by surface coordination complexes of polyethyleneimine-capped Au nanoparticles

A new simple colorimetric chemosensor for sensitive and selective detection of Cu2+ using polyethyleneimine (PEI)-capped Au nanoparticles (PEI/Au NPs) has been developed. PEI/Au NPs are synthesized by using PEI as reducer without adding nanoparticles seeds and stabilizing agent. Copper ions are captured by the amino groups of the PEI/Au NPs to form an absorbent complex at the surface of PEI/Au NPs, resulting in the color of PEI/Au NPs changing from wine red to purple. Under the optimal conditions, the proposed colorimetric sensor is capable of sensitively and specifically detecting Cu2+ with a detection limit of 0.29μM and a linear range of 25–300μM. This method is simple, fast and highly selective for Cu2+ in the presence of high concentrations of other environmentally relevant metal ions because of the great specific coordination between Cu2+ and PEI, which potentially meets the requirement of the detection in real samples. Moreover, addition of EDTA to PEI/Au NPs-Cu2+ recovers the color offering PEI/Au NPs as a promising reversible sensor for practical application.

A colorimetric chemosensor based on new water-soluble PODIPY dye for Hg2+ detection

Abstract The phosphorus-containing PODIPY 1 as a chemosensor can detect Hg 2+ by a color change from pink to violet red without the use of any instrumentation. PODIPY 1 was selective to Hg 2+ with a remarkable absorption change, and addition of other relevant metal ions caused almost no absorption change. The new PODIPY dye 1 was sensitive to various concentrations of Hg 2+ . The energy gap between the HOMO and LUMO of the metal complex 1 –Hg 2+ is smaller than that of chemosensor 1 , which is in good agreement with the red shift in the absorption observed upon treatment of 1 with Hg 2+ . The 1 -based test strips were easily fabricated and low-cost, useful in practical and efficient Hg 2+ test kits.

A colorimetric and fluorescent probe for multiple transition metal ions (Cu2+, Zn2+ and Ni2+): Fast response and high selectivity

A multi-metal colorimetric and fluorescent sensor based on Schiff base bearing an “O-N-N”-coordination site was developed. This newly designed sensor is a highly sensitive and selective “turn-on” fluorescent chemosensor towards Zn2+ which is less affected by physiologically relevant metal ions, especially Cd2+. The cell imaging experiment further confirmed that the sensor could be used for monitoring trace Zn2+ in living cells. On the other hand, evident color changes can be observed from colorless to yellow, orange and purple upon the sensor selective binding with Cu2+, Zn2+ and Ni2+, respectively. The corresponding color changes can be directly discriminated by “naked eye”. Significant response from spectral shift provided distinctly different profiles for each of the three metal ions. Overall, the sensor could simultaneously detect and differentiate three transition metal ions through fluorogenic (Zn2+) and chromogenic (Cu2+, Zn2+ and Ni2+) methods in real time and the detection limit was as low as 10−8M in aqueous medium.

Potentiometric and spectroscopic study of the interaction of 3d transition metal ions with inositol hexakisphosphate

Among myo-inositol phosphates, the most abundant in nature is the myo-inositol hexakisphosphate, InsP6. Although it is known to be vital to cell functioning, the biochemical research into its metabolism needs chemical and structural analysis of all the protonation, complexation and precipitation processes that it undergoes in the biological media. In view of its high negative charge at physiological level, our group has been leading a thorough research into the InsP6 chemical and structural behavior in the presence of the alkali and alkaline earth metal ions essential for life. The aim of this article is to extend these studies, dealing with the chemical and structural features of the InsP6 interaction with biologically relevant 3d transition metal ions (Fe(II), Fe(III), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II)), in a non-interacting medium and under simulated physiological conditions. The metal-complex stability constants were determined by potentiometry, showing under ligand-excess conditions the formation of mononuclear species in different protonation states. Under metal ion excess, polymetallic species were detected for Fe(II), Fe(III), Zn(II) and Cu(II). Additionally, the 31P NMR and UV–vis spectroscopic studies provided interesting structural aspects of the strong metal ion-InsP6 interaction.

Assembly Pathway and Characterization of the RAG1/2-DNA Paired and Signal-end Complexes

Mammalian immune receptor diversity is established via a unique restricted set of site-specific DNA rearrangements in lymphoid cells, known as V(D)J recombination. The lymphoid-specific RAG1-RAG2 protein complex (RAG1/2) initiates this process by binding to two types of recombination signal sequences (RSS), 12RSS and 23RSS, and cleaving at the boundaries of RSS and V, D, or J gene segments, which are to be assembled into immunoglobulins and T-cell receptors. Here we dissect the ordered assembly of the RAG1/2 heterotetramer with 12RSS and 23RSS DNAs. We find that RAG1/2 binds only a single 12RSS or 23RSS and reserves the second DNA-binding site specifically for the complementary RSS, to form a paired complex that reflects the known 12/23 rule of V(D)J recombination. The assembled RAG1/2 paired complex is active in the presence of Mg(2+), the physiologically relevant metal ion, in nicking and double-strand cleavage of both RSS DNAs to produce a signal-end complex. We report here the purification and initial crystallization of the RAG1/2 signal-end complex for atomic-resolution structure elucidation. Strict pairing of the 12RSS and 23RSS at the binding step, together with information from the crystal structure of RAG1/2, leads to a molecular explanation of the 12/23 rule.

A novel method for expression and purification of authentic amyloid-β with and without 15N labels

Amyloid-β (Aβ) is a major constituent in the senile plaques of patients with Alzheimer’s disease (AD). Aβ has been intensively studied in amyloid research; however, challenges posed by data reproducibility arise from purity of synthetic Aβ and high expense for its isotope-labeling. The difficulties motivate development and optimization of recombinant Aβ (rAβ) production. Here, we report a new procedure to express and purify high quality rAβ40 from Escherichia coli. The new Aβ construct expressed insoluble Aβ fused with an N-terminal histidine-tag connected by a linker harboring TEV protease cut site. After purification and partial refolding, the fusion tag was removed by TEV protease cleavage, immobilized metal affinity chromatography (IMAC), and reversed phase-HPLC purification with a yield of 3.5mg/L culture with and without 15N label. The rAβ adopts classic amyloid fibrillization and is capable of binding to its clinical relevant metal ions.

A fluorescent chemosensor for Hg(2+) and Cd(2+) ions in aqueous medium under physiological pH and its applications in imaging living cells.

A new BODIPY derivative with 2,2'-(ethane-1,2-diylbis(oxy))bis(N,N-bis(pyridine-2-ylmethyl)aniline unit as the metal receptor has been designed and synthesized. The dye selectively detects either Cd(2+) or Hg(2+) ions in the presence of hosts of other biologically important and environmentally relevant metal ions in aqueous medium at physiological pH. Binding of metal ions causes a change in the emission behavior of the dye from weakly fluorescent to highly fluorescent. Confocal microscopic experiments validate that the dye can be used to identify changes in either Hg(2+) or Cd(2+) levels in living cells.

Recognition of Al3+ based on a naphthalene-based “Off–On” chemosensor in near 100% aqueous media

An efficient fluorescent Al3+ sensor, 2-hydroxy-1-naphthylaldehyde nicotinoyl hydrazone (HL) has been designed and synthesized. The receptor shows “off–on” fluorescent responses toward Al3+ in near 100% aqueous media. Other relevant metal ions such as Li+, Na+, K+, Ca2+, Mg2+, Cu2+, Co2+, Mn2+, Ni2+, Zn2+, Ba2+, Fe2+, Cd2+, Hg2+, Pb2+, Sc3+, Fe3+, Cr3+ caused almost no fluorescence increase. The reason for this phenomenon is that the addition of Al3+ to the solution of HL induce the formation of a 1:1 stoichiometry of the binding mode of L-Al(III) which inhibits the excited-state intramolecular proton transfer (ESIPT) and photoinduced electron transfer (PET). More importantly, the reversibility of the recognition process of HL was performed by adding a Al3+ bonding agent Na2EDTA.

Morphology-directing synthesis of rhodamine-based fluorophore microstructures and application toward extra- and intracellular detection of Hg(2+).

A new, easily synthesizable rhodamine-based chemosensor with potential N2O2 donor atoms, L(3), has been characterized by single-crystal X-ray diffraction together with (1)H NMR and high-resolution mass spectrometry (HRMS) studies. L(3) was found to bind selectively and reversibly to the highly toxic Hg(2+) ion. The binding stoichiometry and formation constant of the sensor toward Hg(2+) were determined by various techniques, including UV-vis, fluorescence, and Job's studies, and substantiated by HRMS methods. None of the biologically relevant and toxic heavy metal ions interfered with the detection of Hg(2+) ion. The limit of detection of Hg(2+)calculated by the 3σ method was 1.62 nM. The biocompatibility of L(3) with respect to its good solubility in mixed organic/aqueous media (MeCN/H2O) and cell permeability with no or negligible cytotoxicity provides good opportunities for in vitro/in vivo cell imaging studies. As the probe is poorly soluble in pure water, an attempt was made to frame nano/microstructures in the absence and in the presence of sodium dodecyl sulfate (SDS) as a soft template, which was found to be very useful in synthesizing morphologically interesting L(3) microcrystals. In pure water, micro-organization of L(3) indeed occurred with block-shaped morphology very similar to that in the presence of SDS as a template. However, when we added Hg(2+) to the solution of L(3) under the above two conditions, the morphologies of the microstructures were slightly different; in the first case, a flowerlike structure was observed, and in second case, a simple well-defined spherical microstructure was obtained. Optical microscopy revealed a dotlike microstructure for L(3)-SDS assemblies, which changed to a panicle microstructure in the presence of Hg(2+). UV-vis absorption and steady-state and time-resolved fluorescence studies were also carried out in the absence and presence of Hg(2+), and also the SDS concentration was varied at fixed concentrations of the receptor and guest. The results revealed that the fluorescence intensity increased steadily with [SDS] until it became saturated at ∼7 mM SDS, indicating that the extent of perturbation to the emissive species increases with the increase in [SDS] until it becomes thermodynamically stable. There was also an increase in anisotropy with increasing SDS concentration, which clearly manifests the restriction of movement of the probe in the presence of SDS.

Highly Selective and Sensitive Detection of Hg(II) from HgCl2 by a Simple Rhodamine-Based Fluorescent Sensor.

N-acryloyl rhodamine B hydrazide, a non-responsive control of a colorimetric Cu(2+) sensor, was used as a turn-on fluorescent sensor for Hg(II) from HgCl2 in the presence of AgNO3. The detection was highly selective and sensitive, and a large number of environmentally and biologically relevant metal ions, such as Na(+), K(+), Ca(2+), Mg(2+), Fe(3+), Cu(2+), Zn(2+), Cr(3+), Pb(2+), Ni(2+), Fe(2+), Mn(2+), Co(2+), Cd(2+), including Hg(II) from the easy dissociated salts, did not show significant interference. The fluorescence of the sensor (10μM) was enhanced 74 folds by 10 equiv. of Hg(II) from HgCl2 in THF/HAc-NaAc (1/1, v/v, pH = 6) aqueous buffer solution containing 20 equiv. of AgNO3. The maximal fluorescence intensity increased linearly with the concentration of Hg(II) in the range of 0-70μM. The detection limit of Hg(II) was 0.59μM. The sensing mechanism was explored by Job's plot experiment, reversible experiment, mass spectrum analysis, spectroscopic analysis, and thin-layer chromatography.

Thermodynamic properties of molybdate ion: reaction cycles and experiments

Abstract Standard molar quantities of molybdate ion entropy, S m 0 , $S_{\rm{m}}^0,$ enthalpy of formation, Δ f H m o , ${\Delta _{\rm{f}}}H_m^{\rm{o}},$ and Gibbs energy of formation, Δ f G m o , ${\Delta _{\rm{f}}}G_{\rm{m}}^{\rm{o}},$ are key data for the thermodynamic properties of molybdenum compounds and complexes, which are at present investigated by an OECD NEA review project. The most reliable method to determine Δ f H m o ${\Delta _{\rm{f}}}H_{\rm{m}}^{\rm{o}}$ of molybdate ion and alkali molybdates directly consists in measuring calorimetrically the enthalpy of dissolution of crystallized molybdenum trioxide and anhydrous alkali molybdates in corresponding aqueous alkali metal hydroxide solutions. Solubility equilibria of sparingly soluble alkaline earth molybdates and silver molybdate lead to trustworthy data for Δ f G m o ${\Delta _{\rm{f}}}G_{\rm{m}}^{\rm{o}}$ of molybdate ion. Thereby the Gibbs energies of the metal molybdates and the corresponding metal ions are combined with the Gibbs energies of dissolution. As reliable values are available for Δ f G m o ${\Delta _{\rm{f}}}G_{\rm{m}}^{\rm{o}}$ of the relevant metal ions the problem reduces to select the best values of solubility constants and Δ f G m o ${\Delta _{\rm{f}}}G_{\rm{m}}^{\rm{o}}$ of alkaline earth molybdates and silver molybdate. There are two independent possibilities to achieve the latter task. (1) Δ f H m o ${\Delta _{\rm{f}}}H_{\rm{m}}^{\rm{o}}$ for alkaline earth molybdates and silver molybdate have been determined by solution calorimetry. Entropy data of molybdenum have been compiled and evaluated recently. CODATA key values are available for S m o $S_{\rm{m}}^{\rm{o}}$ of the other elements involved. Whereas S m o ( CaMoO 4 , cr ) $S_{\rm{m}}^{\rm{o}}({\rm{CaMo}}{{\rm{O}}_4},{\rm{ cr}})$ is well known since decades, low-temperature heat capacity measurements had to be performed recently, but now reliable values for S m o $S_{\rm{m}}^{\rm{o}}$ of Ag2MoO4(cr), BaMoO4(cr) and SrMoO4(cr) are available. (2) Δ f H m o ( BaMoO 4 , cr ) , ${\Delta _{\rm{f}}}H_{\rm{m}}^{\rm{o}}({\rm{BaMo}}{{\rm{O}}_4},{\rm{ cr}}),$ for example, can be obtained from high temperature equilibria also, but the result is less accurate than that of the first method. Once Gibbs energy of formation, Δ f G m o , ${\Delta _{\rm{f}}}G_{\rm{m}}^{\rm{o}},$ and enthalpy of formation, Δ f H m o , ${\Delta _{\rm{f}}}H_{\rm{m}}^{\rm{o}},$ of molybdate ion are known its standard entropy, S m o , $S_{\rm{m}}^{\rm{o}},$ can be calculated.

Coumarine–imino–C2-glucosyl conjugate as receptor for Cu2+ in blood serum milieu, on silica gel sheet and in Hep G2 cells and the characterization of the species of recognition

A coumarine–imino–C2-glucosyl conjugate (L) was synthesized and characterized. The conjugate L is found to recognize Cu2+ in aqueous HEPES buffer by exhibiting a 95% fluorescence quenching in pH range 7–10 even in the presence of several biologically and ecologically relevant metal ions. Fluorescence on–off behavior has been clearly demonstrated on the basis of the binding variability of Cu2+ to L. The binding has been elicited through the changes observed in fluorescence, absorption, ESI-MS and 1H NMR titrations. All the other thirteen metal ions studied did not show any change in the fluorescence emission. These ions do not interfere with the recognition of Cu2+ by L. The structural features of [CuL]2 complex in both the isomeric forms were established by DFT computational calculations. The utility of L has been demonstrated by showing its sensitivity toward Cu2+ on a thin layer of silica gel. The L gives sensitive fluorescence signals for Cu2+ even in blood serum and exhibits appropriate fluorescence responses in living cells.

Universal buffers for use in biochemistry and biophysical experiments.

The use of buffers that mimic biological solutions is a foundation of biochemical and biophysical studies. However, buffering agents have both specific and nonspecific interactions with proteins. Buffer molecules can induce changes in conformational equilibria, dynamic behavior, and catalytic properties merely by their presence in solution. This effect is of concern because many of the standard experiments used to investigate protein structure and function involve changing solution conditions such as pH and/or temperature. In experiments in which pH is varied, it is common practice to switch buffering agents so that the pH is within the working range of the weak acid and conjugate base. If multiple buffers are used, it is not always possible to decouple buffer induced change from pH or temperature induced change. We have developed a series of mixed biological buffers for protein analysis that can be used across a broad pH range, are compatible with biologically relevant metal ions, and avoid complications that may arise from changing the small molecule composition of buffers when pH is used as an experimental variable.

A colorimetric and turn-on fluorescent chemosensor for selective detection of Hg2+: theoretical studies and intracellular applications

A new colorimetric, “turn-on” fluorescent chemosensor (DEAS-BPH) was synthesized for selective and sensitive recognition of Hg2+ ions with no interference from environmentally relevant metal ions in a mixed organo-aqueous medium.

A new selective chromogenic and turn-on fluorogenic probe for copper(II) in solution and vero cells: recognition of sulphide by [CuL

A new coumarin-appended thioimidazole-linked imine conjugate, viz. has been synthesized and characterized. has been found to recognize Cu(2+) selectively among a wide range of biologically relevant metal ions. The chemosensing behavior of has been demonstrated through fluorescence, absorption, visual fluorescence color changes, ESI-MS and (1)H NMR titrations. The chemosensor showed selectivity toward Cu(2+) by switch on fluorescence among the 18 metal ions studied with a detection limit of 1.53 μM. The complex formed between and Cu(2+) is found to be 1 : 1 on the basis of absorption and fluorescence titrations and was confirmed by ESI-MS. DFT and TDDFT calculations were performed in order to demonstrate the structure of and [CuL] and the electronic properties of chemosensor and its copper complex. This highly fluorescent [CuL] complex has been used to recognize sulphide selectively among the other allied anions. Microstructural features of and its Cu(2+) complex have been investigated by SEM imaging (scanning electron microscopy). The biological applications of were evaluated in Vero cells and it was found to exhibit low cytotoxicity and good membrane permeability for the detection of Cu(2+).