Influence of residual sodium ions on the structure and properties of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a promising conducting polymer in terms of its applicability to transparent and flexible electronic devices. Generally, a negatively charged PSS chain can interact with alkali metal cations like sodium and potassium. During polymerization, these ions, especially sodium ions, remain in an aqueous state and affect particle formation. This paper describes the effect of residual sodium ions on the synthesis of PEDOT:PSS and its electrical and optical properties. Removing the sodium ions weakens the coulombic interaction between the PEDOT and PSS chains, which leads to a linear conformation. This conformational change enhances the electrical conductivity and work function. Furthermore, transmittance in the visible region increased remarkably because the intrinsic electrical properties of the PEDOT:PSS particles were improved. Moreover, the colloidal stability was enhanced because the particle coagulation caused by residual sodium ions was reduced. In summary, we determined that sodium ions in PEDOT:PSS have a considerable influence on its electrical and optical properties and colloidal stability for practical applications.

In this study, we investigated the effects of metal ions, namely sodium ions, on the structure of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) during polymerization and the resulting electrical and optical properties.     

Flavonoid–Metal Ion Complexes: A Novel Class of Therapeutic Agents

Flavonoids are among the most investigated phytochemicals due to their pharmacological and therapeutic activities. Their ability to chelate with metal ions has resulted in the emergence of a new category of molecules with a broader spectrum of pharmacological activities. However, the biological significance of these flavonoid–metal ion complexes is yet to be completely explored. Moreover, no concerted efforts have been made to elucidate their molecular targets and mechanisms of action. This review attempts to provide a snapshot of the various biological activities reported for flavonoid–metal ion complexes and their potential as therapeutic agents. Understanding the mechanism of action and the influence of structure will provide a strong basis to design novel flavonoid–metal ion complexes of therapeutic significance.     

Metal oxide QD based ultrasensitive microsphere fluorescent sensor for copper,chromium and iron ions in water

Herein we developed a rapid, cheap, and water-soluble ultra-sensitive ZnO quantum dot (QD) based metal sensor for detecting different hazardous metal ions up to the picomolar range in water. Various spectroscopic and microscopic techniques confirmed the formation of 2.15 ± 0.46 μm of ZnO QD conjugated CMC microspheres (ZCM microspheres) which contain 5.5 ± 0.5 nm fluorescent zinc oxide (ZnO) QDs. Our system, as a promising sensor, exhibited excellent photostability and affinity towards various heavy metal ions. The detection limits were calculated to be 16 pM for Cu²⁺ and 0.18 nM for Cr⁶⁺ ions which are better than previously reported values. The simple fluorescence ‘turn off’ property of our ZCM microsphere sensor system can serve a two-in-one purpose by not only detecting the heavy metals but also quantifying them. Nonetheless, pattern recognition for different heavy metals helped us to detect and identify multiple heavy metal ions. Finally, their practical applications on real samples also demonstrated that the ZCM sensor can be effectively utilized for detection of Cr⁶⁺, Fe³⁺, Cu²⁺ present in the real water samples. This study may inspire future research and design of target fluorescent metal oxide QDs with specific functions.

Herein we developed a rapid, cheap, and water-soluble ultra-sensitive ZnO quantum dot (QD) based metal sensor for detecting different hazardous metal ions up to the picomolar range in water.     

1H and 51V NMR investigations of the molecular nature of implant-derived vanadium ions in osteoarthritic knee-joint synovial fluid

BACKGROUND: High field (1)H and (51)V NMR spectroscopies were employed to determine the oxidation state and complexation status of vanadium ions in intact osteoarthritic knee-joint synovial fluid (OA SF) when pre-added as V(III)((aq.)), V(IV)((aq.)) and V(V)((aq.)). METHODS: Aliquots of each vanadium solution were added to the SF samples and their (1)H NMR spectra recorded. (51)V NMR spectra were also recorded for the samples to which V(III)((aq.)) had been added. Theoretical computer simulations of the competitive complexation of vanadium ions by a range of low-molecular-mass biomolecules were also performed. RESULTS: The spectroscopic results demonstrated that addition of vanadium ions to intact OA SF gave rise to their complexation by a range of low-molecular-mass biomolecules. The results indicated the physiologically-significant complexing abilities of histidine, threonine, glycine, tyrosine and citrate for each of the added metal ions. The computer simulations revealed that the relative capacity of OA SF complexants to compete for available V(III), V(IV) and V(V) ions reflected the thermodynamic stability constants for such complexes and their available concentrations in this biofluid. CONCLUSIONS: Since comparatively low concentrations of added metal ion are required to selectively influence spectral properties, the "speciation" of prostheses-derived metal ions in biofluids and tissues can be ascertained through the facile employment of high resolution NMR spectroscopy.     

An l-cystine/l-cysteine impregnated nanofiltration membrane with the superior performance of an anchoring heavy metal in wastewater

Considerable efforts are being made to develop new materials and technologies for the efficient and fast removal of toxic ions in drinking water. In this work, we developed a sulfur-complexed strategy to enhance the removal capability of heavy metal ions using the polyamide nanofiltration membrane by the covalent anchoring of l-cystine and l-cysteine. The sulfur-functionalized polyamide nanofiltration membrane exhibits superior complexation of heavy metal ions and can efficiently remove them from high-concentration wastewater. As a result, the sulfur-functionalized nanofiltration membrane not only showed excellent desalination performance but also achieved a record removal rate of heavy metal ions (99.99%), which can effectively reduce Hg(ii) concentration from 10 ppm to an extremely low level of 0.18 ppb, well below the acceptable limits in drinking water (2 ppb). Moreover, the sulfur-functionalized nanofiltration membrane showed an exciting long-term stability and can be easily regenerated without significant loss of Hg(ii) removal efficiency even after six cycles. Such outstanding performances were attributed to the synthetic effect of Hg–S coordinative interaction, electrostatic repulsion, and the sieving action of nanopores. These results highlight the tremendous potential of thiol/disulfide-functionalized NF active layer as an appealing platform for removing heavy metal ions from polluted water with high performance in environmental remediation.

Considerable efforts are being made to develop new materials and technologies for the efficient and fast removal of toxic ions in drinking water.     

Rational design of sequestered DNAzyme beacons to enable flexible control of catalytic activities

DNAzymes as functional units play increasingly important roles for DNA nanotechnology, and fine control of the catalytic activities of DNAzymes is a crucial element in the design and construction of functional and dynamic devices. So far, attempts to control cleavage kinetics can be mainly achieved through varying the concentrations of the specific metal ions. Here we present a facile sequestered DNAzyme beacon strategy based on precisely blocking the catalytic core of the DNAzyme, which can flexibly regulate the DNAzyme cleavage kinetics without changing the concentrations of metal ions. This strategy can be extended to couple with a large number of other RNA-cleaving DNAzymes and was successfully applied in designing a dual stem-loop structure probe for arbitrary sequence biosensing, which provides the possibility of scaling up versatile and dynamic DNA devices that use DNAzymes as functional modules.

We present a sequestered DNAzyme beacon strategy based on precisely blocking the catalytic core for flexible regulation of DNAzyme kinetics.     

Fluid and electrolyte transport across the peritoneal membrane during CAPD according to the three-pore model.

In the present review, we summarize the principles governing the transport of fluid and electrolytes across the peritoneum during continuous ambulatory peritoneal dialysis (CAPD) in "average" patients and during ultrafiltration failure (UFF), according to the three-pore model of peritoneal transport. The UF volume curves as a function of dwell time [V(t)] are determined in their early phase by the glucose osmotic conductance [product of the UF coefficient (LpS) and the glucose reflection coefficient (sigmag)] of the peritoneum; in their middle portion by intraperitoneal volume and glucose diffusivity; and in their late portion by the LpS, Starling forces, and lymph flow. The most common cause of UFF is increased transport of small solutes (glucose) across the peritoneum, whereas the LpS is only moderately affected. Concerning peritoneal ion transport, ions that are already more or less fully equilibrated across the membrane at the start of the dwell, such as Na+ (Cl-), Ca2+, and Mg2+, have a convection-dominated transport. The removal of these ions is proportional to UF volume (approximately 10 mmol/L Na+ and 0.12 mmol/L Ca2+ removed per deciliter UF in 4 hours). The present article examines the impact on fluid and solute transport of varying concentrations of Ca2+ and Na+ in peritoneal dialysis solutions. Particularly, the effect of "ultralow" sodium solutions on transport and UF is simulated and discussed. Ions with high initial concentration gradients across the peritoneum, such as K+, phosphate, and bicarbonate, display a diffusion-dominated transport. The transport of these ions can be adequately described by non-electrolyte equations. However, for ions that are in (or near) their diffusion equilibrium over the peritoneum (Na+, Ca2+, Mg2+), more complex ion transport equations need to be used. Due to the complexity of these equations, however, non-electrolyte transport formalism is commonly employed, which leads to a marked underestimation of mass transfer area coefficients (PS). This can be avoided by determining the PS when transperitoneal ion concentration gradients are steep.     

Time-dependent synergism of five-component mixture systems of aminoglycoside antibiotics to Vibrio qinghaiensis sp.-Q67 induced by a key component

A large number of antibiotics are entering the aquatic environment accompanying human and animal excreta, which will threaten the survival of aquatic organisms and even human health. It has been found that binary mixtures of aminoglycoside (AG) exhibit additive action and can be evaluated well by a classical model, concentration addition (CA) in our past study. Therefore, to investigate the toxicity interaction within multi-component mixtures of AG antibiotics, five antibiotics, kanamycin sulfate (KAN), neomycin sulfate (NEO), tobramycin (TOB), streptomycin sulfate (STS), and gentamicin sulfate (GEN), were selected to construct five-component mixture systems by a uniform design ray method. The toxic effects (luminescence inhibition) of single antibiotic and five-antibiotic mixture systems towards a photobacterium Vibrio qinghaiensis sp.-Q67 (V. qinghaiensis) in different exposure time (0.25, 2, 4, 8, and 12 h) were determined by the time-dependent microplate toxicity analysis method. The concentration-effect data were fitted by a nonlinear least square method, toxicity interaction within mixture systems was analyzed by a CA model, and the interaction intensity was characterized by deviation from the CA model (dCA). Besides, the toxicity mechanism of five antibiotics and their five-component mixtures to V. qinghaiensis was analyzed by electron microscopy. The results show that toxicity of five antibiotics and their five-component mixture systems to V. qinghaiensis is time-dependent and has strong long-term toxicity. Different from binary AG antibiotic mixture systems, five-antibiotic mixture systems exhibit obviously time-dependent synergism. In addition, toxicity of the five-antibiotic mixtures can be 1.4 times higher than that of the mixtures without synergisms at the same concentration level. According to dCA, synergism intensity (dCA) curves of rays move slowly from the high concentration region to the medium or lower one and the maximum dCA values also increase, decrease, or first increase, then decrease with the lengthening of exposure time. The inhibition activity and synergism intensity of mixture rays have good correlation with the concentration ratios of STS, the key component for synergism. The cell morphology of V. qinghaiensis indicates the strong toxicity of five antibiotics and their mixture rays is not due to the destruction of cell structure, but the inhibition of the light-emitting activity of the photobacterium.

There was time-dependent synergism in the five-component mixture systems of five antibiotics, which induced by STS.     

Active Insolubilized Antibiotics Based on Cellulose-Metal Chelates

Cellulose was converted into a more reactive form by chelation with the transition metals titanium(III), iron(III), tin(IV), vanadium(III), and zirconium(IV). The remaining unsubstituted ligands of the transition metal ions were found to be amenable to replacement by electron-donating groups of antibiotic molecules. Ampicillin, gentamicin, kanamycin, neomycin, paromomycin, polymyxin B, and streptomycin were used as antibacterial antibiotics, and amphotericin B and natamycin were used as antifungal antibiotics. Antibacterial activity of the products was tested against two gram-positive and two gram-negative bacteria, and antifungal activity was tested against four fungi. That the antibacterial antibiotics had complexed with the cellulose-metal chelates was demonstrated in that the product cellulose-metal-antibiotic chelates exhibited antibiotic activities whereas the metal chelates of cellulose themselves were inactive. Of 140 tests conducted, cellulose-metal-antibiotic chelates were active in 102 cases. Since the antibiotic derivatives were water insoluble and in fact retain some of the antibacterial activities of the parent compounds, the chelation method provides a facile way of rendering cellulose surfaces, etc., resistant to microbial attack over and above that degree of protection afforded by noncovalent adsorption of the antibiotic to cellulose itself. The underlying principles of the chelation reactions involved are discussed in detail.     

Formation of functional nanobiocatalysts with a novel and encouraging immobilization approach and their versatile bioanalytical applications

The discovery of functional organic–inorganic hybrid nanoflowers (FNFs) consisting of proteins/enzymes as the organic components and Cu(ii) ion as the inorganic component has made an enormous impact on enzyme immobilization studies. The FNFs synthesized by an encouraging and novel approach not only showed high stabilities but also much enhanced catalytic activities as compared to free and conventionally immobilized enzymes. A recent development demonstrated that FNF formation has moved beyond the initial discovery in which enzymes and Cu²⁺ ions used as the organic and inorganic parts, respectively, are replaced with new organic (chitosan, amino acid and plant extracts) and inorganic (Cu²⁺ and Fe²⁺) materials. The new organic materials incorporated into FNFs act as Fenton-like agents and then show peroxidase-like activity owing to the metal ions and the porous structure of FNFs in the presence of hydrogen peroxide (H₂O₂). All FNFs have been widely utilized in many different scientific and industrial fields due to their greatly enhanced activities and stabilities. This review focuses primarily on the preparation, characterization, and bioanalytical applications of FNFs and explains the mechanisms of their formation and enhanced activities and stabilities.

The discovery of functional organic–inorganic hybrid nanoflowers (FNFs) consisting of proteins/enzymes as the organic components and Cu(ii) ion as the inorganic component has made an enormous impact on enzyme immobilization studies.     

Visual artificial tongue for identification of various metal ions in mixtures and real water samples: a colorimetric sensor array using off-the-shelf dyes

A three-unit colorimetric sensor array in aim of detecting heavy metal ions has been constructed with two off-the-shelf dyes. Multivariate data analysis is performed using LDA and HCA to recognize colour change patterns based on both absorption spectra and RGB values from image scans. The sensor array is able to differentiate 15 metal ions not only in separate solutions, but also mixtures of 3, 5, and 7 different metal ions and real water samples.

A colorimetric sensor array was constructed to detect metal ions by pattern recognition based on image analysis and absorption spectra.

Pollution of heavy metal ions in water and soil has become a worldwide environmental concern, due to their great harm to animal and human health even at low concentrations. Hence, to identify and distinguish heavy metal ions both qualitatively and quantitatively has been a field of constant research interest. Traditional methods for heavy metal ion detection such as inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectroscopy (AAS) are, although accurate and most common, very unpractical for on-site testing. A more convenient technique is continuously under demand.Inspired by mammalian olfactory and gustatory systems, array-based sensing platforms, which use a series of cross-reactive sensors instead of specific probes, have emerged as promising alternatives due to their simple fabrication, flexibility, convenient data collection and analysis. Sensor arrays have been reported to distinguish combinations of many analytes and mixtures,^1,2 including physical stimuli (temperature, humidity, light), volatile organic compounds, explosives, toxic industrial chemicals, metal ions, flavonoids, biomolecules (biothiols, phosphates), pesticides, proteins, pathogens (virus, bacteria, fungi), cells, food and beverages (liquors, teas, milks, red wines, coffees, whiskies), herbal medicines, and disease biomarkers.^3–7For metal ions discrimination and quantification, there are different analytical methods to construct response patterns, including electrochemical methods,⁸ steady-state and time-resolved fluorescence spectroscopy,^9–14 UV-visible absorption spectroscopy,^15,16 and digital imaging and colour calibration.^17–21 Although most reported work successfully distinguished samples of single metal ions or mixtures of up to 3 metal ions, applicable methods for analysis of mixtures consisting of more than 3 metal ions as well as real water samples are still of great challenge.Herein, we developed a simple and cost-effective three-unit colorimetric sensor array (Scheme 1) using dithizone in two solvent conditions and resazurin (structures shown in Fig. 1), to distinguish 15 different metal ions, their mixtures, as well as real water samples. Pattern recognition based on data from absorption spectra as well as scanned-images was realized using linear discriminant analysis (LDA) and hierarchical clustering analysis (HCA).Open in a separate windowScheme 1Schematic illustration of colorimetric sensor array for detection of metal ions.Open in a separate windowFig. 1Structures of the two off-the-shelf dyes used in our sensor array.Dithizone was reported to show different colour responses towards diverse metal ions, including Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Mn²⁺ Ag⁺, Cd²⁺, and Hg²⁺.^22–24 Yet its application as a practical sensing molecule for metal ions is limited by its poor solubility in aqueous solution. CTAB was found to improve dithizone''s sensitivity for metal ions detection by favouring dissolution and interaction of dithizone with metal ions.^25,26 Moreover, the pH value of the solution was also reported to influence the property of dithizone, which causes distinct absorption spectral change and colour alteration.²⁷ Thus, we introduced NaOH to the second unit to generate multidimensional information. These different solvent conditions were screened with varying amounts of the surfactant CTAB and NaOH in HEPES for the optimization of dithizone sensing. Based on the results of preliminary experiments (Fig. S1^†), dithizone/CTAB (unit 1: 30 μM of dithizone and 90 μM of CTAB in HEPES buffer) and dithizone/CTAB/NaOH (unit 2: 30 μM of dithizone, 10 mM of CTAB, and 6 mM of NaOH in HEPES buffer) were used as two sensor units in the array. Resazurin was reported capable of discriminating different metal ions based on its voltammetric behaviour.²⁸ Thus we also included it in our sensor array as unit 3 (unit 3: 24.5 μM of resazurin in water).To test the proof-of-concept of the proposed three-unit sensor array, 15 metal ions (Pb²⁺, Ag⁺, Cr³⁺, Cd²⁺, Fe³⁺, As(iii), Zn²⁺, Ni²⁺, Cu²⁺, Mn²⁺, Ba²⁺, Al²⁺, Co²⁺, Sn²⁺, Hg²⁺, each at 5 μM), were selected as analytes. In our study, data were acquired by two different methods, using microplate reader to generate absorption spectral measurement, as well as using flatbed scanner to obtain RGB values in images. Compared to common colorimetric methods which require complex instrumentation, the latter method above demonstrated its convenience by its simple operation, straightforward visualization effect, and good sensitivity. Firstly, the real digital images of the three-unit sensor array upon adding single metal ions at the concentration of 5 μM were recorded by a commercially available and cheap flatbed scanner (Fig. 2A). For each well on the plate, the red, green, and blue (RGB) values from the centre were extracted using our program written in Python (version 3.7.3). The changes of RGB values with and without metal ions, ΔR, ΔG, and ΔB, were used to generate the false-colour images (Fig. 2B) and the corresponding heat map (Fig. 2C). Obvious colour change can be seen in the presence of Ni²⁺, As(iii), Hg²⁺, Co²⁺, Cu²⁺, Zn²⁺, Fe³⁺, Cr³⁺, while only subtle changes take place in the presence of Sn²⁺, Al³⁺, Cd²⁺, Ba²⁺. These different responses presumably result from the different interactions between the sensor units and metal ions.Open in a separate windowFig. 2Performance of sensor array to 15 metal ions single solutions based on colour image change pattern (A) colour image of sensor array recorded by flatbed scanner upon addition of metal ions. (B) Colour difference map of the sensor array. For purposes of visualization, the colour range of the difference map was expanded from 4 to 8 bits per colour (RGB range of 0–58 expanded to 0–255). (C) Heatmap derived from the difference map. (D) LDA 2D plot and (E) HCA dendrogram derived from the colour response pattern of sensor array. Concentration of all used metal ions is 5 μM.LDA was then applied to further digitize and visualize the colour change patterns. LDA is a statistical analysis method that can visually differentiate two or more kinds of objects or events based on their linear combination of features, selected so as to maximize the ratio of inter-class variance to intra-class variance. All metal ions at the concentration of 5 μM were tested using four replicate measurements to provide a training matrix of sixteen samples (fifteen metal ions + one control) × three sensors × three colour channels × four replicates. The resulting training data were analysed and processed through LDA using Sci-kit learn package (version 0.21.2) in Python and transformed into nine canonical scores, which account for 58.23%, 21.32%, 15.40%, 3.53%, 0.82%, 0.38%, 0.16%, 0.10%, 0.04% of variations, respectively. The first two factors accounted for 79.55% of the total variance and were used to construct the two-dimensional (2-D) discrimination plot (Fig. 2D). All the metal ions can be separately grouped with clarity, despite the relatively close between clusters of Al³⁺, Sn²⁺, Fe³⁺ and the high proximity between clusters of Pb²⁺ and Ba²⁺ (as shown in the magnified inset of Fig. 2D).HCA is a common method to build a hierarchy of clusters according to their similarity characterized by the Euclidean distance. Unlike LDA, in which only a few most significant factors are used to do the visualization (in this case, the first three factors accounted for the 91.12% variance of the total), HCA takes all the features into consideration when computing the Euclidean distance among samples. As shown in Fig. 2E, HCA resulted in clear discrimination of 15 metal ions and the control with no misclassification, confirming that the proposed sensor array has strong discrimination ability of these 15 metal ions.Then “leave-one-out” cross-validation was used to evaluate the prediction ability of the LDA classifier. The training set was prepared by removing each sample one at a time, and the LDA model was built on the “leave-one-out” training set. Then the removed sample was reclassified using the LDA model. According to the classification result, the percentage of correct classification by the LDA model would be calculated. In this study, leave-one-out cross-validation for the LDA classification mode showed 100% accuracy for prediction of 15 metal ions at the concentration of 5 μM.As a comparison, UV-vis absorption spectra of the array upon adding these metal ions at the same concentrations were measured using a microplate reader and the response patterns were analysed as well. The patterns of the absorbance change were obtained as (A₀ − A)/A₀, in which A₀ and A are the absorbance without and with metal ions, respectively, in the following equation in specific wavelength range for each sensor unit. As shown in Fig. S2,^† three units responded differently to addition of different metal ions. In order to maximize the spectral information as well as minimize the influence of noise, 61 wavelengths (350–650 nm, every 5 nm) of the first unit, and 55 wavelengths (350–620 nm, every 5 nm) of the other two units were selected for further analysis respectively. Similarly, LDA, “leave-one-out” cross validation, and HCA were applied to characterize the absorbance change patterns. All samples were completely separated into different clusters (Fig. S3^†), including the clusters of Pb²⁺ and Ba²⁺, which were in high proximity in the RGB data analysis. The improved classification performance presumably arose from the higher sensitivity of the microplate reader than that of ordinary flatbed scanner. The image analysis makes a practical alternative to the absorption analysis, with 100% accuracy in both “leave-one-out” cross-validation and HCA in our study. To the best of our knowledge, this three-unit sensor array is by far the simplest one, which is able to discriminate 15 metal ions at such a low concentration. In addition, to evaluate the robustness of our proposed array, double-blind test was carried out to identify 30 unknown metal ion samples. The results (Table S1^†) showed that identification accuracy of 93.33% was achieved, which confirms the feasibility of this sensor array to identify unknown metal ions.Further exploration of the potential application of this array in quantitative analysis was carried out using both image analysis and absorption analysis. Among these fifteen metal ions, Ni²⁺, Cu²⁺, Hg²⁺ (Fig. 3) and Co²⁺ (Fig. S4^†) showed good correlations in LDA 2-D figures. As shown in Fig. 3(A, C and E) for Ni²⁺, Cu²⁺ and Hg²⁺, the 2-D plots using the first two factors displayed clear separations for different concentrations. Plotting factor 1 (the most significant factor) vs. concentrations of these three metal ions showed a good correlation, with the linear detection ranges for Ni²⁺, Cu²⁺ and Hg²⁺ at 0–4 μM, 0–8 μM and 0.5–3 μM, respectively. The results highly suggest that our proposed sensor array might find its potential application in quantitative analysis of some metal ions. Similar results from absorption spectral data analysis were also obtained with higher sensitivity (Fig. S5^†).Open in a separate windowFig. 3Discrimination of Ni²⁺, Cu²⁺ and Hg²⁺ at different concentrations. (A, C and E) LDA plots for the detection of metal ions at different concentrations. (B, D and F) The relationship between factor 1 and different concentrations of metal ions.Distinguishing mixture samples with different composition of metal ions is a great challenge for sensor arrays. Inspired by the strategy of mixture preparation in Bushdid et al. work.²⁹ We prepared 15 pairs of mixtures (referred to as “mixture A” and “mixture B”) that consist of 3, 5 and 7 components drawn from the collection of 15 metal ions (Fig. S6 and Table S2^†). To generate each mixture, we combined these components together at equal ratios. The most apparent difference between two pairs of mixtures with the same number of components is the percentage of components they share which varied from 0 to (N − 1/N) (N represents the number of components of the mixture pair). The components in each mixture were randomly selected by a written python program, and the concentration of each component in all mixtures was fixed at 5 μM. Fig. S7^† and 4(A, C and E) shows that different pairs displayed distinct colour change patterns, which arose from the different components of the mixtures. LDA 2-D plots demonstrated that all pairs of mixtures with the same number of components were completely separated (Fig. 4B, E and F). The “leave-one-out” cross-validation reached 100% accuracy and all the samples were clustered correctly in HCA (Fig. S8^†). The discrimination capability of image analysis was comparable to that of absorption spectral data analysis (Fig. S9^†). These results exhibited the potential of the proposed array as an advanced sensor array which can provide discrimination of highly similar complex mixtures.Open in a separate windowFig. 4Colour change profile of mixture A (left) and mixture B (right) of 15 different metal ions mixture pairs including (A) 3 metal ions, (C) 5 metal ions and (E) 7 metal ions. For purposes of visualization, the colour range of the difference map was expanded from 4 to 8 bits per colour (RGB range of 0–77 expanded to 0–255). LDA plot of sensor array against metal ions mixture pairs consists of exactly (B) 3 components, (D) 5 components and (F) 7 components using RGB channels.Detection of metal ions in real environmental water source are of greater practical significance than lab-prepared samples.To explore the capacity of our array in practical application, real water samples were tested in our study. 7 real water samples including super pure water (SPW), deionized water (DW), tap water (TW), lake water (LW), artificial lake water (ALW), river water (RW) and sea water (SW) were collected and directly tested without intentionally adding any metal ions. LDA 2-D plot demonstrated that all samples were correctly clustered and completely separated (Fig. 5A), while HCA showed clear discrimination of all real water samples with no misclassification (Fig. 5B), which was in accordance with the results of absorption spectral data analysis (Fig. S10^†). The successful differentiation of real water samples revealed the potential for on-site analysis.Open in a separate windowFig. 5Performance of the sensor array on distinguishing real water samples. (A) 2D LDA plot and (B) HCA dendrogram using RGB change values.In conclusion, we fabricated a new three-unit colorimetric sensor array using two commercially available low-cost dyes for detection of heavy metal ions in aqueous solution. In addition to commonly used absorption spectral measurements, colorimetric change patterns were also successfully constructed by imaging analysis of RGB values. LDA and HCA results proved that this array could achieve 100% accuracy in discriminating 15 metal ions solutions at 5 μM. Quantitative analysis of several ions was achieved at sub-micromolar range. Mixtures of 3, 5 and 7 metal ions as well as 7 real water samples without additional spiked metal ions were also accurately differentiated by imaging analysis, suggesting that this array has potential for on-site metal ions detection.     

Stretchable self-healing hydrogels capable of heavy metal ion scavenging

Self-healing hydrogels were prepared by simply mixing phytic acid (PA) and chitosan (CS) in water. Determined by scanning electron microscopy (SEM), the hydrogels were found to be a three-dimensional (3D) porous network structure. The formation of the network structure was considered to be mainly driven by electrostatic interactions and hydrogen bonding, cooperating with the subtle balance of multiple noncovalent interactions. The rheological data indicated that the hydrogels presented excellent mechanical properties with an elastic modulus of 20 000 Pa and a yield stress exceeding 7000 Pa. The dynamic dissociation and recombination of hydrogen bonding and electrostatic interaction in fractured regions of the gels initiated the self-healable property of PA/CS hydrogels. Since PA had high coordination ability to metal ions, PA/CS hydrogels were shown to exhibit excellent capability for capturing heavy metal ions, for example, Pb²⁺ and Cd²⁺. The PA/CS hydrogels provided a simple, green, and high efficiency strategic approach to scavenging heavy-metal ions from industrial sewage.

Stretchable PA/CS polymer hydrogels with multiresponsiveness presented rapid self-healing behavior, and can be used for metal ions scavenging.     

Aggregation of biologically important peptides and proteins: inhibition or acceleration depending on protein and metal ion concentrations

The process of aggregation of proteins and peptides is dependent on the concentration of proteins, and the rate of aggregation can be altered by the presence of metal ions, but this dependence is not always a straightforward relationship. In general, aggregation does not occur under normal physiological conditions, yet it can be induced in the presence of certain metal ions. However, the extent of the influence of metal ion interactions on protein aggregation has not yet been fully comprehended. A consensus has thus been difficult to reach because the acceleration/inhibition of the aggregation of proteins in the presence of metal ions depends on several factors such as pH and the concentration of the aggregated proteins involved as well as metal concentration level of metal ions. Metal ions, like Cu²⁺, Zn²⁺, Pb²⁺etc. may either accelerate or inhibit aggregation simply because the experimental conditions affect the behavior of biomolecules. It is clear that understanding the relationship between metal ion concentration and protein aggregation will prove useful for future scientific applications. This review focuses on the dependence of the aggregation of selected important biomolecules (peptides and proteins) on metal ion concentrations. We review proteins that are prone to aggregation, the result of which can cause serious neurodegenerative disorders. Furthering our understanding of the relationship between metal ion concentration and protein aggregation will prove useful for future scientific applications, such as finding therapies for neurodegenerative diseases.

The process of aggregation of proteins and peptides is dependent on the concentration of proteins, and the rate of aggregation can be altered by the presence of metal ions, but this dependence is not always a straightforward relationship.     

Effect of serum on the in vitro activities of 11 broad-spectrum antibiotics.

We evaluated the effect of serum on the in vitro activities of 11 antimicrobial agents against gram-negative isolates obtained from 100 patients with nosocomial bacteremia. The test organisms included 25 stains of Pseudomonas aeruginosa and 75 strains of the family Enterobacteriaceae. MICs were determined by broth microdilution with Mueller-Hinton broth alone or supplemented with 25 or 50% pooled, heat-inactivated human serum (25S or 50S, respectively). Among the antibiotics evaluated, the protein binding ranged from 9 to 95%. The antibiotics tested and their MICs for 90% of the strains tested in 50S included ciprofloxacin (0.12 micrograms/ml), ceftazidime (1 micrograms/ml), imipenem (1 micrograms/ml), aztreonam (4 micrograms/ml), cefpirome (4 micrograms/ml), cefotaxime (16 micrograms/ml), cefoperazone (16 micrograms/ml), desacetylcefotaxime plus cefotaxime (32 micrograms/ml), ceftriaxone (greater than 32 micrograms/ml), ticarcillin (128 micrograms/ml), and desacetylcefotaxime (greater than 128 micrograms/ml). MICs for 90% of the strains tested were calculated with 95% confidence intervals to show the precision of the MICs for these strains. With the exceptions of ceftriaxone (greater than 95% protein bound) and cefoperazone (90% protein bound), serum had no significant effect on the in vitro activities of various agents. A fourfold-or-greater increase in the MIC of ceftriaxone was observed in 45 of 100 isolates with 50S and in 30 of 100 isolates with 25S. With cefoperazone, 17 of 100 isolates demonstrated more than 2 twofold dilution increases in 50S. Testing of antibiotics which were less protein bound illustrated minor effects primarily with members of the Enterobacteriaceae. The presence of serum did not adversely affect the in vitro activities of broad-spectrum agents against these nosocomial isolates.     

Chelating Agents in Medicine

Abstract

In recent years there has been a growing awareness of the importance of trace metals in the environment, in their dichotomous role as essential nutritional factors on the one hand, and as toxic agents on the other. The apparent ambivalent nature of metal ions is shown as a continuum in a wide range dose-response curve. The response on the curve, being a function of dosage, covers survival of the organism through a deficiency state to normal health, toxicity, and death. This particular review deals with the toxic effects of this dose-response curve and the use of chelating agents to remove execessive quantities of metal ions which are producing toxic effects. The metals discussed include: (1) Heavy metal ions-lead, mercury, and cadmium; (2) essential trace metals in toxic excessive quantities-chromium, cobalt, copper, iron, manganese, molybdenum, selenium, and zinc; (3) less common toxic metal ions-aluminum, antimony, arsenic, beryllium, nickel, tellurium, thallium, and tin. Radioactive metals are also discussed. Chelation therapy is a form of treatment aimed at removing a metal ion from a molecular site at which it is producing a bio chemical lesion. The in vivo stability of a metal chelate is affected by its stability constant, hydrogen ion concentration (pH), competition for and by other metal ions and ligands, tendency of the metal to form insoluble hydroxides, distribution and metabolism of the chelate, and competition of endogenous biochemicals for complexing the metal ion. Speciation studies greatly assist this assessment. Effective chelation therapy depends upon the selection of an appropriate chelating agent for the controlled removal of an undesirable metal ion. The ligands most commonly used in metal ion detoxification include dimercaprol or BAL, unithiol, penicillamine, polyaminocarboxylic acids (EDTA series), desferrioxamine, and dithizone. Toxicity is generally a function of either the metal chelate or of the ligand removing essential metal ions. Chelation therapy is a safe procedure when properly administered. Toxic reactions are most commonly encountered when the clinician uses excessive dosages too rapidly. Chelation therapy should be administered slowly and the treatments spaced with sufficient time lapsing to permit the body to adjust, and the trace element status of the patient monitored throughout.     

A selective detection approach for copper(ii) ions using a hydrazone-based colorimetric sensor: spectroscopic and DFT study

The development of an efficient and miniaturized analytical approach to determine trace levels of toxic ions in aqueous fluids presents a current research challenge. Hydrazone-based chemosensors are considered potential candidates due to their high sensitivity and selectivity towards heavy metal ions. Computational techniques can be properly implemented to elucidate possible modes of ligand–metal interaction and provide an in-depth understanding of the chemistry involved. The present study reports the use of 3-hydroxy-5-nitrobenzaldehyde-4-hydroxybenzoylhydrazone (3-HNHBH) ligand for highly sensitive, quick and re-usable colorimetric sensing of copper(ii) ions in aqueous media. DFT calculations suggest that the complexation of 3-HNHBH with copper(ii) ions adopts a seesaw coordination geometry and results in the largest HOMO–LUMO gap and most effective coulombic interaction compared to Zn and Ni counterparts. It demonstrated a high selectivity towards copper ions with a detection limit of 0.34 μg L⁻¹. The ligand was readily regenerated using a 0.5 M HCl solution, indicating its feasibility to be used as a re-usable sensor for the convenient detection of copper ions in aqueous media. The influence of metal interference, pH and solvents on the selectivity and regeneration of the ligand was also investigated.

The development of an efficient and miniaturized analytical approach to determine trace levels of toxic ions in aqueous fluids presents a current research challenge.     

PrP (58–93) peptide from unstructured N-terminal domain of human prion protein forms amyloid-like fibrillar structures in the presence of Zn2+ ions

Many transition metal ions modulate the aggregation of different amyloid peptides. Substoichiometric zinc concentrations can inhibit aggregation, while an excess of zinc can accelerate the formation of cytotoxic fibrils. In this study, we report the fibrillization of the octarepeat domain to amyloid-like structures. Interestingly, this self-assembling process occurred only in the presence of Zn(ii) ions. The formed peptide aggregates are able to bind amyloid specific dyes thioflavin T and Congo red. Atomic force microscopy and transmission electron microscopy revealed the formation of long, fibrillar structures. X-ray diffraction and Fourier transform infrared spectroscopy studies of the formed assemblies confirmed the presence of cross-β structure. Two-component analysis of synchrotron radiation SAXS data provided the evidence for a direct decrease in monomeric peptide species content and an increase in the fraction of aggregates as a function of Zn(ii) concentration. These results could shed light on Zn(ii) as a toxic agent and on the metal ion induced protein misfolding in prion diseases.

Zinc ions modulate the aggregation of PrP (58–93) amyloid peptide.     

The antibiotic pipeline for multi-drug resistant gram negative bacteria: what can we expect?

Introduction: A real concern in the medical community is the increasing resistance of bacteria, especially that of Gram-negative types. New antibiotics are currently under clinical development, promising to tackle severe infections caused, especially, by multi-drug resistant (MDR) bacteria and broaden the armamentarium of clinicians.

Areas covered: We searched PUBMED and GOOGLE databases. Combinations of already approved β-lactams or monobactams with new β-lactamase inhibitors [imipenem-cilastatin/MK-7655 (relebactam), meropenem/RPX7009 (vaborbactam), ceftaroline/avibactam, aztreonam/avibactam], new β-lactams (S-649266, BAL30072), aminoglycosides (plazomicin), quinolones (finafloxacin) and tetracyclines (eravacycline) were included in the review.

Expert commentary: For the majority of the upcoming antibiotics the currently available data is limited to their microbiology and pharmacokinetics. Their effectiveness and safety against infections due to MDR bacteria remain to be proved. Significant issues are also the impact of these antibiotics on the human intestinal microbiota and their possible co-administration with already-known antimicrobial agents in difficult-to-treat-infections; further studies should be conducted for these objectives.     

Active Immobilized Antibiotics Based on Metal Hydroxides

The water-insoluble hydroxides of zirconium (IV), titanium (IV), titanium (III), iron (II), vanadium (III), and tin (II) have been used to prepare insoluble derivatives of a cyclic peptide antibiotic by a facile chelation process. Testing of the antibacterial activities of the products against two gram-positive and two gram-negative bacteria showed that in the majority of cases the water-insoluble antibiotics remained active against those bacteria susceptible to the parent antibiotic. The power of the assay system has been extended by the novel use of colored organisms to aid determinations where the growth of normal organisms could not be distinguished from the appearance of the supporting material. Insoluble derivatives of neomycin, polymyxin B, streptomycin, ampicillin, penicillin G, and chloramphenicol were prepared by chelation with zirconium hydroxide, and these derivatives similarly reflected the antibacterial activities of the parent compounds. Several of the metal hydroxides themselves possess antibacterial activity due to complex formation with the bacteria. However, the use of selected metal hydroxides can afford a simple, inexpensive, and inert matrix for antibiotic immobilization, resulting in an antibacterial product that may possess slow-release properties. The mechanisms by which the metal hydroxide-antibiotic association-dissociation may occur are discussed.