Interaction Of Zn2 Research Articles

A turn-on fluorescence sensor based on water-soluble amino-pyridyl-benzothiazole-derivatives for measuring cellular Zn2+

Novel amino-pyridyl-benzothiazole-derivatives (PBT) were synthesized through cycloaddition/nucleophilic aromatic substitution reactions for the development of a turn-on fluorescence chemosensor that accurately determines Zn2+ in polar media. The selectivity, water-solubility, and overall analytical response were systematically optimized through incorporation of different aliphatic amines as substituents: pyrrolidine (PBT-Pyn), ethylenediamine (PBT-Et) or 1,3-propylenediamine (PBT-Pr). Those ligands presented intense dual radiative emissions in the blue/green region upon activation with a 395 nm LED, which were attributed to the local excitation and internal energy transfer states. Although no variations were observed upon the interaction of Zn2+ with PBT-Pyn, both turn-off and turn-on responses were observed upon its interaction with PBT-Et. These responses depended on the ligand concentration and the associated inner filter effects. Thereby, PBT-Pr was selected for a deeper evaluation towards photoluminescence determination of Zn2+ due to its exclusive turn-on response and major sensibility obtained at pH 7.0, making it very convenient for analysis in physiological media. Under those conditions, the detection limits were 1.9 µM and 4.7 µM for measurements in aqueous or ethanolic solutions, respectively, with linear ranges up to 40 and 80 μM. The selectivity and good biocompatibility of the chemosensor were demonstrated through cell-viability assays with MCF-7, 3T3-L1 and HT-29 cell lines. The probe was then applied for the real-time epifluorescence imaging of Zn2+, observing emission intensities and distribution profiles that correlated with the concentration and location of the target within living cells.

Selective Detection of Zn2+ Ions by Ratiometric Receptor (E)-N′-(1-(2, 5-Dihydroxy phenyl) Ethylidene) Isonicotinohydrazide: A DFT Study

The metal ion sensing characteristics of a novel Schiff-based ratiometric UV-visible chemosensor (E)-N’-(1-(2,5-dihydroxy phenyl)ethylidene) isonicotinohydrazide) (R1) has been explored. In EtOH:H2O (7:3, v/v), it has high sensitivity and selectivity for Zn2+ among a series of metal ions. With the addition of Zn2+ ions solution, R1 displayed discriminating spectral activity. The other metal ions did not affect R1 in any way. Furthermore, the addition of Zn2+ ions to R1 and LMCT action caused the shifting of the peak to a longer wavelength of 406 nm. The interaction of Zn2+ ions with R1 was further investigated using Density Functional Theory (DFT) investigations. Zn2+-R1 combination has a lower energy (2.2667 kcal.mol-1 to 0.9339 kcal.mol-1) than R1, indicating a strong connection with excellent stability. The Zn2+-R1 complex’s association constant (Ka) was discovered to be 6795M-1 and 6836M-1 using Benesi-Hildebrand and Scatchard plots respectively. The detection limit was determined to be 276 nM.

Performance optimization of CuO-ZnO ceramic electrode on the electrocoagulation of wastewater

Copper oxide (CuO) and zinc oxide (ZnO) were used as a matrix and reinforcement in the compression molding technique to produce conductive ceramic electrodes. CuO-ZnO-based ceramic composites were fabricated through conventional pressing with CuO:ZnO ratios of 75 %:25 %, 80 %:20 %, 85 %:15 %, 90 %:10 %, and 95 %:5 %. CuO and ZnO powders were sieved, dried, mixed, and thencompressed at 300 MPa for 10 min to form a pellet before being burned for 3 h at 800, 900, and 1000 °C in a furnace. The sample's density, porosity, and electrical conductivity were measured. In addition, SEM, XRD analysis, and palm oil wastewater electrocoagulation were carried out. The optimal density value of CuO-ZnO-based ceramic composites ranged from 8.564 × 103 to 9.205 × 103 kg m−3. The optimal composition of the CuO:ZnO in the synthesized composites, namely 95 %:5 %, yielded the lowest porosity values (12.1 %-35.4 %), while the 75 %:25 % composition produced the highest porosity values (20.8 %–88.3 %). The optimum porosity value (12.1 %) was obtained by CuO:ZnO composite composition of 95 %:5 % with a sintering temperature of 1000 °C. This composite also generates a conductivity value of 1.019–16.897 S/m. The interaction of Zn2+ ions from ZnO crystals with CuO crystals increases the size of CuO and ZnO crystals, as determined by XRD analysis. Based on the findings of this study, CuO-ZnO ceramic electrodes could be utilized in industrial wastewater treatment as the water quality test result met the requirements of Minister of Environment Decree No. 51/MENLH/10/1995.

Bifunctional 3-Hydroxy-4-Pyridinones as Potential Selective Iron(III) Chelators: Solution Studies and Comparison with Other Metals of Biological and Environmental Relevance.

The binding ability of five bifunctional 3-hydroxy-4-pyridinones towards Cu2+ and Fe3+ was studied by means of potentiometric and UV–Vis spectrophotometric measurements carried out at I = 0.15 mol L−1 in NaCl(aq), T = 298.15 K and 310.15 K. The data treatments allowed us to determine speciation schemes featured by metal-ligand species with different stoichiometry and stability, owing to the various functional groups present in the 3-hydroxy-4-pyridinones structures, which could potentially participate in the metal complexation, and in the Cu2+ and Fe3+ behaviour in aqueous solution. Furthermore, the sequestering ability and metal chelating affinity of the ligands were investigated by the determination of pL0.5 and pM parameters at different pH conditions. Finally, a comparison between the Cu2+ and Fe3+/3-hydroxy-4-pyridinones data herein presented with those already reported in the literature on the interaction of Zn2+ and Al3+ with the same ligands showed that, from the thermodynamic point of view, the 3-hydroxy-4-pyridinones are particularly selective towards Fe3+ and could therefore be considered promising iron-chelating agents, also avoiding the possibility of competition, and eventually the depletion, of essential metal cations of biological and environmental relevance, such as Cu2+ and Zn2+.

Inhibitory effect of Zn2+ on the chain‐initiation process of cumene oxidation

AbstractCarbon nanotubes (CNTs) have excellent catalytic activity in liquid phase reaction, especially in aerobic oxidation of cumene. In previous work, the conversion of cumene was 41.8% and the selectivity of cumene hydroperoxide was 71.5%, which was catalyzed by CNTs. But a small amount of impurity Zn2+ totally blocked up the aerobic oxidation of cumene that catalyzed by CNTs, which is an unexpected discovery. By analyzing the catalytic mechanism of CNTs, the inhibition effect of Zn2+ is locked on the abstraction of H atom from cumene. The inhibition of Zn2+ is confirmed in two effects by density functional theory calculations. First, due to the strongly coordination of active oxygen species (ROS) by Zn2+, the energy barrier of initial reaction increases to 1.90 eV, which is nearly 4 times higher than that of the only ROS promoted‐process. Second, the interaction of Zn2+ and RO· or ROO· to inhibits the chain propagation reaction of free radicals. This work precisely demonstrates that the inhibition effect of Zn2+ on initial reaction of cumene. The most significant thing is that the effect of metallic heteroatoms is not negligible in organic oxidation reaction.

The effect of combined exposure of zinc and nickel on the development of zebrafish.

Excessive accumulation of Zn2+ or Ni2+ can cause various problems to aquatic animals. In this study, the developmental toxicity induced by individual or combined exposure of Zn2+ and Ni2+ to zebrafish embryos and larvae were evaluated to better understand the interaction between Zn2+ and Ni2+ . Both of individual and combined exposure of Zn2+ and Ni2+ could cause obvious developmental toxicity, which mainly occurred after hatching, at a concentration-dependent manner. The calculated 168-h LC50 were 2.79 mg/L for Zn2+ and 7.44 mg/L for Ni2+ . The interaction of Zn2+ and Ni2+ based on mortality was found to be an antagonism. Various malformations, including tail curving, spinal curvature, pericardial edema, and yolk sac edema, were observed with significant effects on body length and heartbeat rates after exposure of Zn2+ and Ni2+ . Meanwhile, some genes related to cardiovascular development and bone formation were mainly down-regulated by the individual and combined exposure of Zn2+ and Ni2+ . The individual exposure was more toxic than combined exposure because the interaction of Zn2+ and Ni2+ was determined to be an antagonism. The down-regulation of genes related to cardiovascular development and bone formation may contribute to the observed malformation and decreases of body length and heartbeat rates.

Exploring the interactions of iron and zinc with the microtubule binding repeats R1 and R4

The dyshomeostasis of copper, iron and zinc ions in pathological conditions, which are critically involved in many brain activities, may result in an accumulation of them in the brain that has been reported for the patients with Alzheimer's disease. Conformational change is one of the consequences of metal-peptide interaction as we observed for the interaction of the Cu2+ with microtubule binding repeats of tau protein, which ultimately cause peptide aggregation. Herein, we show that interaction of Zn2+, Fe2+, and Fe3+ with full-length tau peptide R1 (tau244–274) and R4 (tau337–368), the first and fourth microtubule binding repeats of tau protein, lead to the conformational changes. And while the Electrospray ionization-mass spectrometry (ESI-MS) confirmed the complexation of Zn2+ and Fe2+ with both R1 and R4, there is no evidence for metalation of R1 or R4 with Fe3+.

Triplet of cysteines – Coordinational riddle?

Polythiol binding of metal ions plays crucial role in the proper functioning of cysteine-rich proteins that are responsible for metal homeostasis and defending processes against metal toxicity (including heavy metals detoxification). The coordination properties of cysteine residues involved in specific sequencional patterns in proteins (like those present in e.g. metallothioneins) are interesting not only from a chemical point of view but may also lead to a better understanding of the purpose and allocation of metal ions in various biomolecules. In this study, the interaction of Zn2+, Cd2+ and Ni2+ ions with four peptides containing cysteine triplet motif were studied by potentiometric and spectroscopic methods. The main goal of this research was to answer the question how effectively three thiols, each being next to other, are able to bind single metal ion. Two of peptides contain additional, fourth cysteine residue, separated from triplet by two and three other amino acid residues. As results show, all three cysteine residues in the CCC motif are able to participate in the coordination of the metal ion (Cd2+, Zn2+). Except cysteine thiol groups, amide nitrogen atoms are also involved in the coordination of Ni2+.

Role of zinc and copper ions in the pathogenetic mechanisms of traumatic brain injury and Alzheimer's disease.

The disruption of homeostasis of zinc (Zn2+) and copper (Cu2+) ions in the central nervous system is involved in the pathogenesis of many neurodegenerative diseases, such as amyotrophic lateral sclerosis, Wilson's, Creutzfeldt-Jakob, Parkinson's, and Alzheimer's diseases (AD), and traumatic brain injury (TBI). The last two pathological conditions of the brain are the most common; moreover, it is possible that TBI is a risk factor for the development of AD. Disruptions of Zn2+ and Cu2+ homeostasis play an important role in the mechanisms of pathogenesis of both TBI and AD. This review attempts to summarize and systematize the currently available research data on this issue. The neurocytotoxicity of Cu2+ and Zn2+, the synergism of the toxic effect of calcium and Zn2+ ions on the mitochondria of neurons, and the interaction of Zn2+ and Cu2+ with β-amyloid (Abeta) and tau protein are considered.

A reversible calix[4]arene armed phenolphthalein based fluorescent probe for the detection of Zn2+ and an application in living cells.

A reversible and easy assembled fluorescent sensor based on calix[4]arene and phenolphthalein (C4P) was developed for selective zinc ion (Zn2+ ) sensing in aqueous samples. The probe C4P demonstrated high selective and sensitive detection towards Zn2+ over other competitive metal ions. Interaction of Zn2+ with a solution of C4P resulted in a considerable increment in emission intensity at 440nm (λex =365nm) due to the suppression of photoinduced electron transfer (PET) process and the restriction of C=N isomerization. The binding constant (Ka ) of C4P with Zn2+ was calculated to be 4.50×1011 M-2 and also the limit of detection of C4P for Zn2+ was as low as 0.108μM (at 10-7 M level). Moreover, the fluorescence imaging in the human colon cancer cells suggested that C4P had great potential to be used to examine Zn2+ in vivo.

Synthesis of fluorescent BSA templated silver nanomaterials and it’s application of detection of Zn2+ and Co2+

In this paper, BSA (bovine serum albumin) was used as stabilizer and protectant to synthesize high fluorescent silver nanoparticles (BSA-AgNPs) in ice bath. A method for the detection of metal ions was developed by using silver nanoparticles as fluorescent probes. The experimental results show that the BSA-AgNPs has unique selectivity for cobalt ions and zinc ions. When the cobalt ion exists in the system, the BSA-AgNPs is destroyed and the fluorescence quenching is caused, and the correlation coefficient is R = 0.970 35 when the concentration of cobalt ion is 100 μmol/L–600 μmol/L, and the correlation coefficient is R = 0.970 35. When the zinc ion exists in the system, the interaction of Zn2+ and BSA leads to the rise of the BSA-AgNPs fluorescein, and the Zn2+ concentration is in the 100 μmol/L–600 μmol/L. BSA-AgNPs shows a good linear relationship. The correlation coefficient is 0.985 90. EDTA can be used as a metal ion chelating agent. The rapid complexation of Co2+ with EDTA blocked the interaction between Co2+ and BSA, and the fluorescence of BSA-AgNPs could be restored. Based on this, the label free detection of zinc ions and cobalt ions was completed. Therefore, the prepared high fluorescence BSA-AgNPs sensor has a good application prospect in ion detection.

Zn(ii)–nucleobase metal–organic nanofibers and nanoflowers: synthesis and photocatalytic application

The interaction of Zn2+ ions with pure nucleobases guanine and cytosine under alkaline conditions leads to the formation of nanoscale metal–organic nanofibers and nanoflowers with excellent photocatalytic activity for the degradation of organic pollutant dyes.

Insights on the interaction of Zn2 + cation with triazoles: Structures, bonding, electronic excitation and applications

At present, we investigate the structures, the stability, the bonding and the spectroscopy of the Zn2+-triazole complexes (Zn2+-Tz), which are subunits of triazolate based porous materials and Zn-enzymes. This theoretical work is performed using ab initio methods and density functional theory (DFT) where dispersion correction is included. Through these benchmarks, we establish the ability and reliability of M05-2X+D3 and PBE0+D3 functionals for the correct description of Zn2+-Tz bond since these DFTs lead to close agreement with post Hartree-Fock methods. Therefore, M05-2X+D3 and PBE0+D3 functionals are recommended for the characterization of larger organometallic complexes formed by Zn and N-rich linkers. For Zn2+-Tz, we found two stable σ-type complexes: (i) a planar structure where Zn2+ links to unprotonated nitrogen and (ii) an out-of-plane cluster where carbon interacts with Zn2+. The most stable isomers consist on a coordinated covalent bond between the lone pair of unprotonated nitrogen and the vacant 4s orbital of Zn2+. The roles of covalent interactions within these complexes are discussed after vibrational, NBO, NPA charges and orbital analyses. The bonding is dominated by charge transfer from Zn2+ to Tz and intramolecular charge transfer, which plays a vital role for the catalytic activity of these complexes. These findings are important to understand, at the microscopic level, the structure and the bonding within triazolate based macromolecular porous materials and Zn-enzymes.

Electrochemical Studies of Zinc/Cysteine Interactions

Introduction The amino acid L-cysteine has been studied because of its role in several biochemical pathways (1). Electrochemical studies are possible due to the redox characteristics of the sulfhydryl group, so that the electrochemical characteristics of L-cysteine can be determined by voltammetric methods (2). In this study, the biochemical importance of zinc(II)/cysteine complexes in proteins (“zinc fingers”) has prompted an investigation of the interaction of ZnSO4with L-cysteine in various media. Experimental L-Cysteine was obtained from Sigma-Aldrich Company, and ZnSO4 .7 H2O was obtained from ThermoFisher Scientific. A Gamry Interface 1000 potentiostat with Gamry Framework software was used to carry out electrochemical experiments. Potentials are referenced against a Ag/AgCl reference electrode. Platinum and glassy carbon electrodes were purchased from BASi. Gold electrodes were obtained from eDAQ. Results and Discussion In a study of the complexation of Zn2+ by L-cysteine in pH 7.4 phosphate buffer, it was found that addition of ZnSO4 . 7 H2O to the buffer solution produced a cloudy appearance due to the low solubility of the resulting Zn3(PO4)2 . Upon addition of L-cysteine, the system was still cloudy at the 1:1 L-cysteine : Zn2+ point; however, at the 2:1 L-cysteine : Zn2+ point, the solution became clear. This behavior evidently occurs because the interaction of Zn2+ with L-cysteine is stronger than is its interaction with phosphate. These results are consistent with Zn(cys)2 complexation reported in the literature (3). The corresponding voltammograms at glassy carbon are shown in Figure 1. For ZnSO4 addition, the scan showed only a very small zinc stripping peak at the negative end of the potential range. At the 1:1 L-cysteine : Zn2+ point, processes are clearly evident for zinc deposition/stripping, and oxidation of complexed L-cysteine is observed at +0.7 V vs Ag/AgCl. This oxidation process is slightly altered compared to that observed for only L-cysteine (no added Zn2+) (2). Similar behavior for the oxidation processes was also observed at gold. Further additions of L-cysteine gave larger currents for the L-cysteine oxidation process. These results support the uptake of zinc ion into the solution as L-cysteine interacts with Zn2+, initially added as ZnSO4 . 7 H2O in pH 7.4 phosphate buffer. References C.K. Mathews, K.E. Van Holde, D.R. Appling, and S. J. Anthony-Cahill, Biochemistry, 4th Edition, Pearson Canada, Toronto, 2013. G. T. Cheek and M. A. Worosz, ECS Transactions, 2016, 72(27), 1-8. S. Foley and M. Enescu, Vibrational Spectroscopy, 2007, 44, 256-265. Figure 1. Cyclic voltammograms at glassy carbon (3 mm diameter) in aqueous pH 7.4 phosphate buffer, 100 mV/s scan rate. [ Dashed red line : ZnSO4 . 7 H2O, 2.1 mM nominal concentration ] [ Solid black line : Addition of 2.4 mM L-cysteine to previous solution ] Figure 1

ESI-MS studies of the non-covalent interactions between biologically important metal ions and N-sulfonylcytosine derivatives.

The aim of this report is to present the electrospray ionization mass spectrometry results of the non-covalent interaction of two biologically active ligands, N-1-(p-toluenesulfonyl)cytosine, 1-TsC, 1 and N-1-methanesulfonylcytosine, 1-MsC, 2 and their Cu(II) complexes Cu(1-TsC-N3)2 Cl2 , 3 and Cu(1-MsC-N3)2 Cl2 and 4 with biologically important cations: Na+ , K+ , Ca2+ , Mg2+ and Zn2+ . The formation of various complex metal ions was observed. The alkali metals Na+ and K+ formed clusters because of electrostatic interactions. Ca2+ and Mg2+ salts produced the tris ligand and mixed ligand complexes. The interaction of Zn2+ with 1-4 produced monometal and dimetal Zn2+ complexes as a result of the affinity of Zn2+ ions toward both O and N atoms. Copyright © 2016 John Wiley & Sons, Ltd.

Agglutination of human erythrocytes by the interaction of Zn2+ion with histidine-651 on the extracellular domain of band 3

Clustering of band 3, chloride/bicarbonate exchanger, has been reported in Zn2+-treated human erythrocytes. However, the agglutination of human erythrocytes is also induced by the interaction of Zn2+ion with histidine on band 3. Identification of histidine that interacts with Zn2+ion remains to be determined. The Zn2+-induced agglutination of human erythrocytes was unaffected by chymotrypsin cleavage of the small loop region containing His-547 in the extracellular domain of band 3. On the other hand, papain digestion of the large loop region containing His-651 in band 3 inhibited such Zn2+-induced agglutination. Moreover, Zn2+-induced erythrocyte agglutination was inhibited by the peptide (ARGWVIHPLG) containing His-651, but not by the peptide such as ARGWVIRPLG, which His-651 was substituted by arginine. Among 10 kinds of animal erythrocytes tested, interestingly, no agglutination by Zn2+ions was observed in cow cells only that the forth amino acid in the upstream from His-669 on the large loop of cow band 3 is aspartate (Asp-665) instead of glycine. As expected, the agglutination of human erythrocytes by Zn2+ ions was inhibited in the presence of aspartate. These data indicate that the interaction of Zn2+ ion with His-651 residue of band 3 plays an important role in the Zn2+-induced agglutination of human erythrocytes.

Conversion of xylose into furfural in a MOF-based mixed matrix membrane reactor

Furfural is regarded as an important platform chemical with a wide range of applications. Because of the low concentration of furfural in the hydrolysate, energy-saving and environmentally friendly separation method is urgently demanded. In this work, a homogeneous mixed matrix membrane (MMM) consisting of Zn2(bim)4 as inorganic filler and PMPS (polymethylphenylsiloxane) as polymer matrix was successfully fabricated by employing a solution-blending method. The vapor permeation experiments demonstrated that the pervaporation separation index (PSI) increased with increasing temperature, indicating the high performance of the as-synthesized Zn2(bim)4-PMPS membrane for separating furfural at high temperature. Hereafter, the dehydration reaction of xylose into furfural in a membrane reactor coupled with Zn2(bim)4-PMPS membrane was carried out. In contrast to the conventional reactor, the furfural yield in membrane reactor kept increasing due to the in-situ recovery of furfural by vapor permeation. The highest furfural yield achieved till now was 41.1% at 140°C in aqueous solution. Owing to the intrinsic separation properties of Zn2(bim)4 crystals and the effective enhancement of membrane stability by interaction of Zn2(bim)4 with PMPS matrix, the Zn2(bim)4-PMPS membrane coupled reactor exhibited better performance than pure PMPS membrane coupled reactor.

Elucidating the mode of action of a typical Ras state 1(T) inhibitor.

The small GTPase Ras is an essential component of signal transduction pathways within the cell, controlling proliferation, differentiation, and apoptosis. Only in the GTP-bound form does Ras interact strongly with effector molecules such as Raf-kinase, thus acting as a molecular switch. In the GTP-bound form, Ras exists in a dynamic equilibrium between at least two distinct conformational states, 1(T) and 2(T), offering different functional properties of the protein. Zn2+-cyclen is a typical state 1(T) inhibitor; i.e., it interacts selectively with Ras in conformational state 1(T), a weak effector binding state. Here we report that active K-Ras4B, which is prominently found to be mutated in human tumors, exhibits a dynamic equilibrium like H-Ras, which can be modulated by Zn2+-cyclen. The titration experiments of Ras with Zn2+-cyclen indicate a cooperatively coupled binding of the ligands to the two interaction sites on Ras that could be identified for H-Ras previously. Our data further indicate that as in state 2(T) where induced fit produces the substate 2(T)* after effector binding, a corresponding substate 1(T)* can be detected at the state 1(T) mutant Ras(T35A). The interaction of Zn2+-cyclen with Ras not only shifts the equilibrium toward the weak effector binding state 1(T) but also perturbs the formation of substate 1(T)*, thus enhancing the inhibitory effect. Although Zn2+-cyclen shows an affinity for Ras in only the millimolar range, its potency of inhibition corresponds to a competitive state 2 inhibitor with micromolar binding affinity. Thus, the results demonstrate the mode of action and potency of this class of allosteric Ras inhibitors.

The effect of Zn2+ on Pelodiscus sinensis creatine kinase: unfolding and aggregation studies

We studied the effects of Zn2+ on creatine kinase from the Chinese soft-shelled turtle, Pelodiscus sinensis (PSCK). Zn2+ inactivated the activity of PSCK (IC50 = .079 ± .004 mM) following first-order kinetics consistent with multiple phases. The spectrofluorimetry results showed that Zn2+ induced significant tertiary structural changes of PSCK with exposure to hydrophobic surfaces and that Zn2+ directly induced PSCK aggregation. The addition of osmolytes such as glycine, proline, and liquaemin successfully blocked PSCK aggregation, recovering the conformation and activity of PSCK. We measured the ORF gene sequence of PSCK by rapid amplification of cDNA end and simulated the 3D structure of PSCK. The results of molecular dynamics simulations showed that eight Zn2+ bind to PSCK and one Zn2+ is predicted to bind in a plausible active site of creatine and ATP. The interaction of Zn2+ with the active site could mostly block the activity of PSCK. Our study provides important insight into the action of Zn2+ on PSCK as well as more insights into the PSCK folding and ligand-binding mechanisms, which could provide important insight into the metabolic enzymes of P. sinensis.

Structural basis behind the interaction of Zn2 + with the protein α-synuclein and the Aβ peptide: A comparative analysis

α-Synuclein (AS) aggregation is associated to neurodegeneration in Parkinson's disease (PD). At the same time, alterations in metal ion homeostasis may play a pivotal role in the progression of AS amyloid assembly and the onset of PD. Elucidation of the structural basis directing AS–metal interactions and their effect on AS aggregation constitutes a key step towards understanding the role of metal ions in AS amyloid formation and neurodegeneration. Despite of the reported evidences that link Zn2+ with the pathophysiology of PD and the fact that this metal ion was shown to promote AS fibrillation in vitro, neither the structural characterization of the binding sites nor the identification of the amino acids involved in the interaction of Zn2+ with the protein AS has been carried out. By using NMR spectroscopy, we have addressed here unknown structural details related to the binding of Zn2+ to the protein AS through the design of site-directed and domain truncated mutants of AS. The binding of zinc to the Aβ peptide was also studied and discussed comparatively. Although the results of this study contribute to the understanding of the structural and molecular basis behind the acceleration of AS fibrillation mediated by Zn2+, the low affinity that characterizes the interaction of Zn2+ with AS contrasts strongly with the high-affinity features reported for the binding of this metal ion to other target proteins linked to human amylodosis such as Aβ peptide and the Islet Amyloid Polypeptide (IAPP), challenging the biological relevance of zinc interactions in the pathogenesis of PD.