Metal Ion Binding Properties Research Articles

Switchable Metal-Ion Selectivity in Sulfur-Functionalised Pillar[5]arenes and Their Host-Guest Complexes.

Nucleophilic substitution of pertosylated pillar[5]arene (P-OTs) with commercially available sulfur containing nucleophiles (KSCN, KSAc, and thiophenol), yields a series of sulfur-functionalised pillar[5]arenes. DLS results and SEM images imply that these pillararene macrocycles self-assemble in acetonitrile solution, while X-ray crystallographic evidence suggests solvent-dependent assembly in the solid state. The nature of the sulfur substituents decorating the rim of the pillararene controls binding affinities towards organic guest encapsulations within the cavity and dictates metal-ion binding properties through the formation of favorable S-M2+ coordination bonds outside the cavity, as determined by 1 H NMR and fluorescence spectroscopic experiments. Addition of a dinitrile guest containing a bis-triazole benzene spacer (btn) induced formation of pseudorotaxane host-guest complexes. Fluorescence emission signals from these discrete macrocycles were significantly attenuated in the presence of either Hg2+ or Cu2+ in solution. Analogous titrations utilizing the corresponding pseudorotaxanes alter the binding selectivity and improve fluorescence sensing sensitivity. In addition, preliminary liquid-liquid extraction studies indicate that the macrocycles facilitate the transfer of Cu2+ from the aqueous to the organic phase in comparison to extraction without pillar[5]arene ligands.

Nesfatin-3 possesses divalent metal ion binding properties, which remain hidden in the nucleobindin-2 precursor protein

BackgroundNucleobindin-2 (Nucb2) is a multidomain protein that, due to its structure, participates in many physiological processes. It was originally identified in several regions of the hypothalamus. However, more recent studies have redefined and extended the function of Nucb2 far beyond its initially observed role as a negative modulator of food intake.ResultsPreviously, we described Nucb2 as structurally divided into two parts: the Zn2+-sensitive N-terminal half and the Ca2+-sensitive C-terminal half. Here, we investigated the structural and biochemical properties of its C-terminal half, which, after posttranslational processing, yields the formation of a fully uncharacterized peptide product known as nesfatin-3. Nesfatin-3 likely contains all the key respective structural regions of Nucb2. Hence, we expected that its molecular properties and affinity toward divalent metal ions might resemble those of Nucb2. Surprisingly, the obtained results showed that the molecular properties of nesftain-3 were completely different from those of its precursor protein. Moreover, we designed our work as a comparative analysis of two nesfatin-3 homologs. We noticed that in their apo forms, both proteins had similar shapes and existed in solution as extended molecules. They both interacted with divalent metal ions, and this interaction manifested itself in a compaction of the protein molecules. Despite their similarities, the differences between the homologous nesfatin-3s were even more informative. Each of them favored interaction with a different metal cation and displayed unique binding affinities compared either to each other or to Nucb2.ConclusionsThe observed alterations suggested different from Nucb2 physiological roles of nesfatin-3 and different impacts on the functioning of the tissues and on metabolism and its control. Our results clearly demonstrated that nesfatin-3 possessed divalent metal ion binding properties, which remained hidden in the nucleobindin-2 precursor protein.

In-vitro evaluation of indigenous probiotic lactobacilli for lead bio-adsorption potential, its tolerance and complex stability

Probiotic lactic acid bacteria exhibit metal ion binding properties, which can be employed as metal bio-adsorbents in the human system. Lead is a prevalent dietary contaminant that causes lead toxicity in humans, especially children. In the present investigation, we evaluated the indigenous lactobacilli for their lead bioadsorption potential that can offer a pre-emptive approach for bioremediating lead toxicity. After standardizing the lead bioadsorption assay, ten probiotic lactobacilli showing lead retention of >80% in the pellet were selected. Statistical correlation analysis on lead bioadsorption assay, factors affecting lead and lead resistance profiling revealed L. plantarum HD 51 as the most potent lead adsorber. Scanning electron microscopy of L. plantarum HD 51 demonstrated that the binding occurred on the bacterial cell wall. Hence L. plantarum HD-51 could be used as a biotherapeutic agent to reduce the body’s burden on lead by sequestering it out of the human body.

Experimental and theoretical study of novel aminobenzamide-aminonaphthalimide fluorescent dyads with a FRET mechanism.

In this work, both experimental and theoretical methods were used to study the photophysical and metal ion binding properties of a series of new aminobenzamide–aminonaphthalimide (2ABZ–ANAPIM) fluorescent dyads. The 2-aminobenzamide (2ABZ) and 6-aminonaphthalimide (ANAPIM) fluorophores were linked through alkyl chains (C2 to C6) to obtain four fluorescent dyads. These dyads present a highly efficient (0.61 to 0.98) Förster Resonant Energy Transfer (FRET) from the 2ABZ to the ANAPIM due to the 2ABZ emission and ANAPIM excitation band overlap and the configurational stacking of both aromatic systems which allows the energy transfer. These dyads interact with Cu2+ and Hg2+ metal ions in solution inhibiting the FRET mechanism by the cooperative coordination of both 2ABZ and ANAPIM moieties. Both experimental and theoretical results are consistent and describe clearly the photophysical and coordination properties of these new dyads.

Mechanistic Insights into Selective Sensing of Pb2+ in Water by Photoluminescent CdS Quantum Dots

The prospect of aqueous polyethyleneimine-capped CdS quantum dots (QDs), in toxic metal-ion sensing, has been explored. Pb2+ binds strongly to the surface of the QDs facilitating ultrafast electron transfer. As a result, severe (∼90%) PL quenching is observed. Hot electron transfer plays an important role in the quenching process, as is elucidated by anticorrelation between the magnitude of ground-state bleach of the QDs and the concentration of Pb2+ ions, as well as the concurrent decrease in bleach rise time. A second major contribution is from electron transfer from conduction band edge, with a rate constant of 1.45 × 1011 s–1. Selectivity in this “turn-off” sensing process is governed by the exergonicity, quality of QD surface, nature of capping ligand, and its metal-ion binding properties. Engineering these factors is crucial for the development of QD-based selective and efficient metal-ion sensors.

A Pentapeptide with Tyrosine Moiety as Fluorescent Chemosensor for Selective Nanomolar-Level Detection of Copper(II) Ions.

Herein, we have investigated principally with the use of UV and fluorescence (steady-state and time-resolved) spectroscopy the interactions between selected pentapeptides with tyrosine residue (EYHHQ, EHYHQ, EHHQY, and KYHHE) and various metal ions (Cu2+, Mn2+, Co2+, Ni2+, Zn2+, Cr3+, Cd2+, Ag+, Pb2+, Sr2+, Ba2+, Ca2+, Mg2+, Al3+, Fe2+, and Ga3+) in order to establish the relationship between the position of a tyrosine residue in the peptide sequence and the metal ion-binding properties. Among the peptides studied, EHYHQ was evaluated as an efficient and selective ligand for developing a chemosensor for the detection of copper(II) ions. While significant fluorescence emission quenching was observed for that peptide in the presence of Cu2+ cations, other metal cations used at the same and at considerably higher concentrations caused a negligible change of the fluorescence emission spectrum, indicating a high selectivity of EHYHQ for Cu2+ ions. Under optimum conditions, fluorescence intensity was inversely proportional to the concentration of Cu2+ ions. The limit of detection of Cu2+ ions with the use of EHYHQ was determined at the level of 26.6 nM. The binding stoichiometry of the complexes of the studied peptides with Cu2+ ions was evaluated spectrophotometrically and fluorimetrically (as in the case of EHYHQ confirmed by mass spectrometry) and found to be 1:2 (Cu2+-peptide) for all the investigated systems. Furthermore, the stability constant (K) values of these complexes were determined. The reversibility of the proposed Cu2+ ions sensor was confirmed, the pH range where the sensor acts was determined, while its analytical performance was compared with some other reported recently fluorescent sensors. The mechanism of the interactions between EHYHQ and Cu2+ was proposed on the basis of NMR spectroscopy investigations.

Curcuma longa rhizome extract mediated unmodified silver nanoparticles as multisensing probe for Hg(II) ions

Sensing of mercury ion which is an environmental and health hazardous metal ion is achieved by microwave assisted silver nanoparticles (AgNP) using curcuma longa rhizome (CLR) extract. The phyto-constituents, especially curcuminoids plays a vital role in the reduction and stabilisation of nanoparticles and provides suitable binding sites for sensing Hg(II) ions. The heavy metal ion binding properties of curcumin help to prevent the toxicity induced by Hg(II) ions. This work emphasizes on the controlled synthesis, characterization and sensing mechanism of CLR-AgNP and its interaction with Hg(II) ion, with the aid of UV–vis. spectroscopy, XRD, FT-IR, TEM, EDX, DLS, fluorescence spectroscopy and electrochemical tools and techniques. The limit of detection for UV–vis. spectroscopic, fluorescence spectroscopic and electrochemical methods are 8.20, 0.50 and 6.50 nM (S/N = 3) respectively, suggesting the enhanced sensitivity of the proposed system towards Hg(II) ions. High selectivity for Hg(II) ions over an extended range of other rival heavy metal ions and successful application in real samples also possible with these techniques. We also attempt to focus on the antibacterial activities of CLR-AgNP against Escherichia coli and Staphylococcus aureus.

Efficient DNA-Catalyzed Porphyrin Metalation for Fluorescent Ratiometric Pb2+ Detection.

Developing biosensors for Pb2+ is an important analytical topic. DNA-based Pb2+ sensors have been designed mainly based on RNA-cleaving DNAzymes and Pb2+-induced folding of G-quadruplex (G4) DNA. Porphyrin metalation is a key reaction in biology and catalysis. Many enzyme mimics have been developed to catalyze this reaction, and some metalation DNAzymes were reported with a G4 structure. Inspired by the excellent G4 binding properties of certain divalent metal ions, we herein screened a few metals and G-rich DNA sequences. The metalation activity of a DNA named T30695 (sequence: (G3T)4) was significantly accelerated by Pb2+. The reaction of Cu2+ insertion into the mesoporphyrin IX had a kcat of 0.89 min-1 and a Km of 9.8 μM, representing a catalytic efficiency similar to that of human ferrochelatase. The reason for the acceleration was attributed to Pb2+ binding of the G4 DNA and the catalytic activity of the large Pb2+ ion for this reaction. A ratiometric sensor for Pb2+ was developed by inserting Zn2+ with a detection limit of 23.5 nM Pb2+. This work has established a new DNA-based reaction that can be used for Pb2+ detection, and it also provides a highly efficient new DNAzyme for porphyrin metalation, which might be used for signal production for other biosensors.

Direct Assembly and Metal-Ion Binding Properties of Oxytocin Monolayer on Gold Surfaces.

Peptides are very common recognition entities that are usually attached to surfaces using multistep processes. These processes require modification of the native peptides and of the substrates. Using functional groups in native peptides for their assembly on surfaces without affecting their biological activity can facilitate the preparation of biosensors. Herein, we present a simple single-step formation of native oxytocin monolayer on gold surface. These surfaces were characterized by atomic force spectroscopy, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy. We took advantage of the native disulfide bridge of the oxytocin for anchoring the peptide to the Au surface, while preserving the metal-ion binding properties. Self-assembled oxytocin monolayer was used by electrochemical impedance spectroscopy for metal-ion sensing leading to subnanomolar sensitivities for zinc or copper ions.

Novel polymeric phthalocyanines bridged flexible 1,5-pentanedithiol unit for metal ions extraction: synthesis, characterization and evaluation

A novel bisphthalonitrile 5,5′-(pentane-1,5-diylbis(sulfanediyl))bis(4-((2-aminophenyl)thio)phthalonitrile) 2 was synthesized by a nucleophilic aromatic substitution of chloro atom of 4-(2′-aminophenyl sulfanyl)-5-chloro-benzene-1,2-dicarbonitrile 1 with dithiol functions of pentane-1,5-dithiole. The synthesis of polymeric phthalocyanine complexes 3 and 4 by cyclotetramerization of bisphthalonitrile derivative 2 were accomplished in the presence of appropriate metal salt in a Schlenk tube containing quinoline under nitrogen atmosphere. The investigation of metal-ion binding properties of bisphthalonitrile 2 and polymeric zinc(II) phthalocyanine 4 was performed by using liquid–liquid extraction procedure for 2 and solid–liquid extraction procedure for 4. Polymeric zinc(II) phthalocyanine 4 was found to extract Ag(II) and Hg(II) with high efficiency. The novel compounds were characterized by a combination of elemental analysis and 1H NMR, 13C NMR, IR, and MS spectral data.

Ester appended organosilatranes: Paradigm for the detection of Cu2+, Pb2+ and Hg2+ ion

A new series of ester appended organosilatranes (5a–f) were developed for the specific and selective detection of Cu2+, Hg2+ and Pb2+ and were well characterized by various spectroscopic techniques. The newly synthesized silatranes (5a–f) were appraised for heavy metal ion binding properties using UV-vis and photoluminescent spectra. In addition the stern volmer plot confirmed the quenching phenomenon on addition of Cu2+, Hg2+ and Pb2+. Interestingly, the detection limit of 5a-f with Cu2+, 5b with Hg2+ and 5d with Pb2+ is 1.07–3.56 µM, 1.43 and 1.65 respectively. In a nutshell, the present article provides the cost-effective and promising platform for detection of these ions.

Benzodifurans for biomedical applications: BZ4, a selective anti-proliferative and anti-amyloid lead compound.

Our goal is to evaluate benzodifuran-based scaffolds for biomedical applications. We here explored the anticancer and anti-amyloid activities of a novel compound (BZ4) in comparison with other known benzodifuran analogs, previously studied in our group, and we have explored its ability to interact with different DNA model systems. BZ4 shows antiproliferative activity on different cancer cells; does not affect noncancerous control cells and alters the aggregation properties of β-amyloid, as ascertained by circular dichroism, fluorescence spectroscopy and scanning electron microscopy analysis. An overall, qualitative picture on the mechanistic aspects related to the biological activities is discussed in light of the dynamic light scattering, UV, circular dichroism and fluorescence data, as well as of the metal ion-binding properties of BZ4.

Contemplating 1,2,4-Thiadiazole-Inspired Cyclic Peptide Mimics: A Computational Investigation

Marine derived cyclic peptides have inspired chemists for decades as the cavitand architecture can be compared with macrocyclic ligands, and hence easily conceived as mediators of metal-ion transport. Lissoclinamide 5 and ascidiacyclamide are two such cyclic peptides that have received much attention both for their metal ion complexation properties and biological activity; the metal ion binding properties of mimics of these two systems have been reported. Reported herein is a computational study aimed at evaluating the stability, and potential for copper(ii) ion binding by lissoclinamide 5 mimics that substitute the naturally occurring 4-carboxy-1,3-thiazole units for novel valine- and phenylalanine-derived 1,2,4-thiadiazole units. Our results suggest that one lissoclinamide 5 mimic, 1,2,4-thiadiazole (TDA)-lissoclinamide 9, may be capable of forming a complex with one CuII ion, [Cu(9-H)(H2O)]+. A complex with two CuII ions, [Cu2(9-H)(μ-OH)]2+, was also considered. These results set the stage for synthetic and experimental metal binding studies.

Chromenone-rhodamine conjugate for naked eye detection of Al3+ and Hg2+ ions in semi aqueous medium

ABSTRACTChromenone-rhodamine conjugate 1 has been synthesized and its metal ion binding properties have been studied in CH3CN/water (3:1, v/v; 10 mM HEPES buffer; pH = 6.85). Compound 1 senses multiple metal ions such as Al3+ and Hg2+ by exhibiting turn on fluorescence and color change (colorless to pink). Al3+ and Hg2+ ions have been distinguished with the aid of tetrabutylammonium iodide (TBAI). While in the presence of I− the pink color of the 1.Hg2+ complex was completely discharged; under identical conditions the pink color of 1.Al3+ complex was retained.

Mutations of Histidine 13 to Arginine and Arginine 5 to Glycine Are Responsible for Different Coordination Sites of Zinc(II) to Human and Murine Peptides.

Because mice and rats do not naturally develop Alzheimer's disease, genetically modified animals are required to study this pathology. This striking difference in terms of disease onset could be due to three alterations in the murine sequence (R5G, Y10F and H13R) of the amyloid-β peptide with respect to the human counterpart. Whether the metal-ion binding properties of the murine peptide are at the origin of such different amyloidogenicity of the two peptides is still an open question. Herein, the main zinc binding site to the murine amyloid-β at physiological pH has been determined through the combination of several spectroscopic and analytical methods applied to a series of six peptides with one or two of the key mutations. These results have been compared with the zinc binding site encountered in the human peptide. A coordination mechanism that demonstrates the importance of the H13R and R5G mutations in the different zinc environments present in the murine and human peptides is proposed. The nature of the minor zinc species present at physiological pH is also suggested for both peptides. Finally, the biological relevance and fallouts of the differences determined in zinc binding to human versus murine amyloid-β are also discussed.

Coumarin–derived Organosilatranes: Functionalization at magnetic silica surface and selective recognition of Hg2+ ion

This article features the first synthesis of coumarin based triazole linked organosilatranes (3–5) derived from terminal alkyne (1) via click methodology. The coumarin tethered organosilatranyl moiety was anchored on magnetic silica surface and was well characterized by numerous spectroscopic and analytical techniques. The resultant hybrid nanoparticles have been characterized in detail by FTIR, UV–vis spectroscopy, Photoluminiscence (P.L), SEM, TEM, XRD, EDX and TGA. The silatranes (3–5) were then assessed for their metal ion binding properties using absorption and emission spectra. It was observed that the synthesized compounds showed significant selectivity for Hg (II). In addition, the interacting ability of coumarin based derivatives was investigated at different pH values and the pH 9 was considered to be the most favorable pH for fluorometric analysis. Importantly, the hybrid nanoparticles possessed enhanced sensorial ability towards Hg2+ ion and these findings were affirmed using stern volmer equation. In addition, the complexation mode of silatrane (3) with Hg2+ ion was also elucidated by computational analysis using DFT study.

Synthesis and Characterization of Polymer Metal Complexes of Cu (II) and Zn (II) with NNMBA Cross-Linked Polyacrylamide Supported L-Aspartic Acid and L-Lysine

Crosslinked polymers with specific properties are widely used as catalyst supports as they are inert, non toxic and non volatile and offer advantageous features of heterogeneous catalysis such as thermal stability, selectivity and recyclability to homogeneous system. The ease of separation from the reaction products lead to operational flexibility. Moreover the amount of metal present on the surface of such catalyst is very small which is of economic significance in the case of expensive metals. Metal ion binding properties of transition metal ions Cu (II) and Zn (II) with amino acids L-Aspartic acid (L-Asp) and L-Lysine (L-Lys) supported 2 mol % N, N'methylene bisacrylamide (NNMBA) crosslinked polyacrylamide have been studied. The swelling studies reveal that they are highly hydrophilic polymeric ligands. The characterization of the polymer, transamidated polymer, and the polymer metal complexes were done by Infra Red (IR), Ultra Violet (UV) and Scanning Electron Microscope (SEM) analysis. From carboxyl capacity measurements, SEM analysis and swelling studies it was established that the more complexation of the metal ion is found with the ligand L-Aspartic acid

Antiviral activity and metal ion-binding properties of some 2-hydroxy-3-methoxyphenyl acylhydrazones.

Here we report on the results obtained from an antiviral screening, including herpes simplex virus, vaccinia virus, vesicular stomatitis virus, Coxsackie B4 virus or respiratory syncytial virus, parainfluenza-3 virus, reovirus-1 and Punta Toro virus, of three 2-hydroxy-3-methoxyphenyl acylhydrazone compounds in three cell lines (i.e. human embryonic lung fibroblast cells, human cervix carcinoma cells, and African Green monkey kidney cells). Interesting antiviral EC50 values are obtained against herpes simplex virus-1 and vaccinia virus. The biological activity of acylhydrazones is often attributed to their metal coordinating abilities, so potentiometric and microcalorimetric studies are here discussed to unravel the behavior of the three 2-hydroxy-3-methoxyphenyl compounds in solution. It is worth of note that the acylhydrazone with the higher affinity for Cu(II) ions shows the best antiviral activity against herpes simplex and vaccinia virus (EC50~1.5µM, minimal cytotoxic concentration=60µM, selectivity index=40).

Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses

Abstract The acyclic nucleoside phosphonate (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC; Cidofovir) has been approved for clinical use in antiviral therapy. We determined the acidity constants of H2(HPMPC)±, as well as that of the nucleobase-free (hydroxy-2-(phosphonomethoxy)propane (H(HPMP)−) (I = 0.1 M, NaNO3; 25 °C). Given that in vivo nucleotides and their analogues participate in reactions typically as metal ion (M2+) complexes, the stability constants of the M(H;HPMPC)+, M(HPMPC), and M(HPMP) complexes with M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ were measured. Comparisons between results for HPMP2− and previous data for PME2− ( CH 3 CH 2 O CH 2 PO 3 2 - ; phosphonomethoxyethane) revealed the hydroxyl-group effect. The hydroxyl group stabilizes only complexes with the heavier alkaline earth metal ions (Ca2+, Sr2+, Ba2+). For all other complexes, the enhanced stability can solely be explained by the formation of 5-membered chelates involving the ether oxygen; these occur in equilibrium with simple 'open' phosphonate-M2+ species. The stability of the M(HPMPC) complexes is also higher than expected for a phosphonate-only coordination, indicating that chelates are formed, but comparison with the HPMP2− data shows that the cytosine base does not affect complex stability. Similar observations were made previously with related cytosine derivatives. The stability data for the monoprotonated M(H;HPMPC)+ complexes suggest that these carry H+ predominantly on the phosphonate group, and M2+ on the nucleobase.

Inhibition of hazardous compound formation in muscle foods by antioxidative phytophenols.

Individual and mixed herbal extracts, as well as plant spices, are widely used in the preparation of muscle foods to enhance the organoleptic attributes. Abundantly rich in phenolic compounds, many of the phytochemical extracts have been shown to possess strong radical-scavenging and metal ion-binding properties and hence exert antioxidant activity in meat products. Because of their antiradical nature, phenolic acids and flavonoids, such as tea catechins, caffeic acid, chlorogenic acid, and mixed polyphenols derived from rosemary, licorice, and other herbal materials, are capable of inhibiting the formation of harmful secondary products from oxidized lipids and proteins. The inactivation of carcinogenic compounds produced in some nitrite-cured and high temperature-processed meats (e.g., nitrosamines and aromatic amines) by phytophenols has also been demonstrated in recent studies. Here, I describe the application of phytochemical-rich food ingredients in prepared meat and discuss the mechanisms by which plant-derived phenolic antioxidants mitigate toxicant and mutagen production in muscle foods.