Conformational alterations in unidirectional ion transport of a light-driven chloride pump revealed using X-ray free electron lasers.

Light-driven chloride-pumping rhodopsins actively transport anions, including various halide ions, across cell membranes. Recent studies using time-resolved serial femtosecond crystallography (TR-SFX) have uncovered the structural changes and ion transfer mechanisms in light-driven cation-pumping rhodopsins. However, the mechanism by which the conformational changes pump an anion to achieve unidirectional ion transport, from the extracellular side to the cytoplasmic side, in anion-pumping rhodopsins remains enigmatic. We have collected TR-SFX data of Nonlabens marinus rhodopsin-3 (NM-R3), derived from a marine flavobacterium, at 10-µs and 1-ms time points after photoexcitation. Our structural analysis reveals the conformational alterations during ion transfer and after ion release. Movements of the retinal chromophore initially displace a conserved tryptophan to the cytoplasmic side of NM-R3, accompanied by a slight shift of the halide ion bound to the retinal. After ion release, the inward movements of helix C and helix G and the lateral displacements of the retinal block access to the extracellular side of NM-R3. Anomalous signal data have also been obtained from NM-R3 crystals containing iodide ions. The anomalous density maps provide insight into the halide binding site for ion transfer in NM-R3.

Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor.

Some residues in the cystic fibrosis transmembrane conductance regulator (CFTR) channel are the site of more than one CFTR variant that cause cystic fibrosis. Here, we investigated the function of S1159F and S1159P, two variants associated with different clinical phenotypes, which affect the same pore-lining residue in transmembrane segment 12 that are both strongly potentiated by ivacaftor when expressed in CFBE41o- bronchial epithelial cells. To study the single-channel behaviour of CFTR, we applied the patch-clamp technique to Chinese hamster ovary cells heterologously expressing CFTR variants incubated at 27°C to enhance channel residence at the plasma membrane. S1159F- and S1159P-CFTR formed Cl- channels activated by cAMP-dependent phosphorylation and gated by ATP that exhibited thermostability at 37°C. Both variants modestly reduced the single-channel conductance of CFTR. By severely attenuating channel gating, S1159F- and S1159P-CFTR reduced the open probability (Po ) of wild-type CFTR by ≥75% at ATP (1 mM); S1159F-CFTR caused the greater decrease in Po consistent with its more severe clinical phenotype. Ivacaftor (10-100 nM) doubled the Po of both CFTR variants without restoring Po values to wild-type levels, but concomitantly, ivacaftor decreased current flow through open channels. For S1159F-CFTR, the reduction of current flow was marked at high (supersaturated) ivacaftor concentrations (0.5-1 µM) and voltage-independent, identifying an additional detrimental action of elevated ivacaftor concentrations. In conclusion, S1159F and S1159P are gating variants, which also affect CFTR processing and conduction, but not stability, necessitating the use of combinations of CFTR modulators to optimally restore their channel activity. KEY POINTS: Dysfunction of the ion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes the genetic disease cystic fibrosis (CF). This study investigated two rare pathogenic CFTR variants, S1159F and S1159P, which affect the same amino acid in CFTR, to understand the molecular basis of disease and response to the CFTR-targeted therapy ivacaftor. Both rare variants diminished CFTR function by modestly reducing current flow through the channel and severely inhibiting ATP-dependent channel gating with S1159F exerting the stronger adverse effect, which correlates with its association with more severe disease. Ivacaftor potentiated channel gating by both rare variants without restoring their activity to wild-type levels, but concurrently reduced current flow through open channels, particularly those of S1159F-CFTR. Our data demonstrate that S1159F and S1159P cause CFTR dysfunction by multiple mechanisms that require combinations of CFTR-targeted therapies to fully restore channel function.

High correlated color temperature artificial lighting impairs retinal pigment epithelium integrity and chloride ion transport: A potential mechanism for choroidal thinning.

Among the environmental factors contributing to myopia, the role of correlated color temperature (CCT) of ambient light emerges as a key element warranting in-depth investigation. The choroid, a highly vascularized and dynamic structure, often undergoes thinning during the progression of myopia, though the precise mechanism remains elusive. The retinal pigment epithelium (RPE), the outermost layer of the retina, plays a pivotal role in regulating the transport of ion and fluid between the subretinal space and the choroid. A hypothesis suggests that variations in choroidal thickness (ChT) may be modulated by transepithelial fluid movement across the RPE. Our experimental results demonstrate that high CCT illumination significantly compromised the integrity of tight junctions in the RPE and disrupted chloride ion transport. This functional impairment of the RPE may lead to a reduction in fluid transfer across the RPE, consequently resulting in choroidal thinning and potentially accelerating axial elongation. Our findings provide support for the crucial role of the RPE in regulating ChT. Furthermore, we emphasize the potential hazards posed by high CCT artificial illumination on the RPE, the choroid, and refractive development, underscoring the importance of developing eye-friendly artificial light sources to aid in the prevention and control of myopia.

Crown Ether Electrolyte Additive Enables High-Rate and Stable Polyviologen Cathode Material for Chloride Ion Batteries.

A variety of inorganic and inorganic cathode materials for chloride ion storage are reported. However, their application in chloride ion batteries (CIB) is hindered by poor rate capability and cycling stability. Herein, an organic poly(butyl viologen dichloride) (PBVCl2) cathode material with significantly enhanced rate and cycling performance in the CIB is achieved using a crown ether (18-Crown-6) additive in the tributylmethylammonium chloride-based electrolyte. The as-prepared PBVCl2 cathodes exhibit impressive capacity increases from 149.4 to 179.1 mAh g-1 at 0.1 C and from 57.8 to 111.9 mAh g-1 at 10 C, demonstrating the best rate performance with the highest energy density among those of various reported cathodes for CIBs. This impressive performance improvement is a result of the great boosts in charge transfer, ion transport, and interface stability of the battery by the use of 18-Crown-6, which also contributes to a more than twofold increase in capacity retention after 120 cycles. The electrode reaction mechanism of the CIB based on highly reversible chloride ion transfer is revealed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy.

Internal Electric Field Facilitates Facet-Dependent Photocatalytic Cl- Utilization on BiOCl in High-Salinity Wastewater for Ammonium Removal.

High Cl- concentration in saline wastewater (e.g., landfill leachate) limits wastewater purification. Catalytic Cl- conversion into reactive chlorine species (RCS) arises as a sustainable strategy, making the salinity profitable for efficient wastewater treatment. Herein, aiming to reveal the structure-property relationship in Cl- utilization, bismuth oxychloride (BiOCl) photocatalysts with coexposed {001} and {110} facets are synthesized. With an increasing {001} ratio, the RCS production efficiency increases from 75.64 to 96.89 µg L-1 min-1. Mechanism investigation demonstrates the fast release of lattice Cl- as an RCS and the compensation of ambient Cl-. Correlation analysis between the internal electric field (IEF, parallel to [001]) and normalized efficiency on {110} (kRCS/S{110}, perpendicular to [001]) displays a coefficient of 0.86, validating that the promoted carrier dynamics eventually affects Cl- conversion on the open layered structure. The BiOCl photocatalyst is well behaved in ammonium (NH4+-N) degradation ranging from 20 to 800 mg N L-1 with different chlorinity (3-12 g L-1 NaCl). The sustainable Cl- conversion into RCS also realizes 85.4% of NH4+-N removal in the treatment of realistic landfill leachate (662 mg of N L-1 NH4+-N). The structure-property relationship provides insights into the design of efficient catalysts for environment remediation using ambient Cl-.

Fluorescent Probe-Based Fiber Optic Sensor for Real-Time Monitoring of Chloride Ions in Coastal Concrete Structures.

Coastal concrete structures, such as cross-sea bridges and tunnels, are susceptible to the penetration of chloride ions, which can lead to the deterioration of the passive film on the rebar surface, consequently accelerating the corrosion process. Conventional methods for monitoring chloride ions typically require in situ drilling for sample collection, thereby compromising efficiency and accuracy. Additionally, real-time monitoring and early warning cannot be achieved. To address these challenges, this work introduces a fluorescent-probe-based fiber optic sensor for monitoring chloride levels in concrete structures. Quinine sulfate was chosen as the fluorescent material due to its exceptional sensitivity to chloride ions and its stability in concrete environments. The proposed sensor was manufactured using sol-gel and 3D-printing techniques. Tests were conducted using concrete simulation fluid and cement mortar specimens. The results demonstrate that the sensitivity of the proposed sensor is greater than 0.01 M, and its accuracy in penetration depth measurement is better than 3 mm. The findings confirm that the designed fiber optic sensor based on quinine sulfate enables real-time monitoring of chloride ions in concrete structures, offering high sensitivity (0.1% in concentration and 2.7 mm in terms of penetration depth), unique selectivity (as it is immune to other ions whose concentrations are 10 times higher than those of Cl-), and a compact size (10 × 20 mm). These attributes render it promising for practical engineering applications.

Boosted Electrocatalytic Degradation of Levofloxacin by Chloride Ions: Performances Evaluation and Mechanism Insight with Different Anodes.

As chloride (Cl-) is a commonly found anion in natural water, it has a significant impact on electrocatalytic oxidation processes; yet, the mechanism of radical transformation on different types of anodes remains unexplored. Therefore, this study aims to investigate the influence of chlorine-containing environments on the electrocatalytic degradation performance of levofloxacin using BDD, Ti4O7, and Ru-Ti electrodes. The comparative analysis of the electrode performance demonstrated that the presence of Cl- improved the removal and mineralization efficiency of levofloxacin on all the electrodes. The enhancement was the most pronounced on the Ti4O7 electrode and the least significant on the Ru-Ti electrode. The evaluation experiments and EPR characterization revealed that the increased generation of hydroxyl radicals and active chlorine played a major role in the degradation process, particularly on the Ti4O7 anode. The electrochemical performance tests indicated that the concentration of Cl- affected the oxygen evolution potentials of the electrode and consequently influenced the formation of hydroxyl radicals. This study elucidates the mechanism of Cl- participation in the electrocatalytic degradation of chlorine-containing organic wastewater. Therefore, the highly chlorine-resistant electrocatalytic anode materials hold great potential for the promotion of the practical application of the electrocatalytic treatment of antibiotic wastewater.

Design of Solid Polycationic Electrolyte to Enable Durable Chloride-Ion Batteries.

The high energy density and cost-effectiveness of chloride-ion batteries (CIBs) make them promising alternatives to lithium-ion batteries. However, the development of CIBs is greatly restricted by the lack of compatible electrolytes to support cost-effective anodes. Herein, we present a rationally designed solid polycationic electrolyte (SPE) to enable room-temperature chloride-ion batteries utilizing aluminum (Al) metal as an anode. This SPE endows the CIB configuration with improved air stability and safety (i.e. free of flammability and liquid leakage). A high ionic conductivity (1.3×10-2 S cm-1 at 25 °C) has been achieved by the well-tailored coordination structure of the SPE. Meanwhile, the solid polycationic electrolyte ensures stable electrodes|electrolyte interfaces, which effectively inhibit the growth of dendrites on the Al anodes and degradation of the FeOCl cathodes. The Al|SPE|FeOCl chloride-ion batteries showcased a high discharge capacity around 250 mAh g-1 (based on the cathodes) and extended lifespan. Our electrolyte design opens a new avenue for developing low-cost chloride-ion batteries.

A High-Nickel Layered Double Hydroxides Cathode Boosting the Rate Capability for Chloride Ion Batteries with Ultralong Cycling Life.

Chloride-ion batteries (CIBs) have drawn growing attention in large-scale energy storage applications owing to their comprehensive merits of high theoretical energy density, dendrite-free characteristic, and abundance of chloride-containing materials. Nonetheless, cathodes for CIBs are plagued by distinct volume effect and sluggish Cl- diffusion kinetics, leading to inferior rate capability and short cycling life. Herein, an unconventional Ni5 Ti-Cl LDH is reported with a high nickel ratio as a cathode material for CIB. The reversible capacity of Ni5 Ti-Cl LDH retains 127.9 mAh g-1 over 1000 cycles at a large current density of 1000 mA g-1 , which exceeds that of ever reported CIBs, with extraordinary low volume change of 1.006% during a whole charge/discharge process. Such superior Cl-storage performance is attributed to synergetic contributions consisting of high redox activity from Ni2+ /Ni3+ and pinning Ti that restrains local structural distortion of LDH host layers and enhances adsorption intensity of chloride atoms during the reversible Cl- intercalation/de-intercalation in LDH gallery, which are revealed by a comprehensive study including X-ray photoelectron spectroscopy, kinetic investigations, and DFT calculations. This work provides an effective strategy to design low-cost LDHs materials for high-performance CIBs, which are also applicable to other types of halide-ion batteries (e.g., fluoride-ion and bromide-ion batteries).

Mechanical properties, durability and environmental assessment of low-carbon cementitious composite with natural fibrous wollastonite.

Cementitious composite is one of the most widely used construction materials around the world, but cement production is accompanied by energy waste and CO2 emission. Wollastonite, a natural fibrous silicate mineral, can be a potential supplementary cementing materials (SCMs) for cementitious composite owing to its similar calcium silicate system, and it has an eco-friendly and convenient production process. Furthermore, its unique fibrous structure can possibly act as reinforcement for the cement matrix. In view of this, this study aimed to investigate the effects of different sizes (the median diameter of 3 µm, 6 µm, 9 µm and 12 µm) and contents (0%, 5%, 10%, 15% and 20% by mass) of wollastonite combined with 5% silica fume on the mechanical strength, durability and microstructure of cementitious composite by compressive test, flexural test, shear test, rapid chloride migration test, sulfate corrosion test, X-ray diffraction(XRD), scanning electron microscope (SEM) and fourier transform infrared spectrometer (FTIR). The results showed that the strength and durability of samples increased and then decreased as wollastonite content increased. An addition of 10% wollastonite into the cement matrix increased compressive strength, flexural strength and shear strength by 6.22%, 29.3% and 18.4%, respectively. However, an addition of 5% wollastonite was found to be more beneficial for improving resistance to chloride and sulfate corrosion. Additionally, samples prepared with 3 µm wollastonite performed better, which can be attributed to the fact that the small size of wollastonite contributed to both the filling effect and the skeletal support and bridging effect of microfibers. The CO2 emissions of cementitious composites decreased as the wollastonite percentage increased. The findings confirm that natural wollastonite as SCMs for cementitious composite has performance enhancement and environmental benefits, however, it is recommended that the wollastonite content should not exceed 15%.

Removal of chloride ion from drinking water using Ag NPs-Modified bentonite: Characterization and optimization of effective parameters by response surface methodology-central composite design.

The presence of chloride ion as an environmental pollutant is having a devastating and irreversible effect on aquatic and terrestrial ecosystems. To ensure safe and clean drinking water, it is vital to remove this substance using non-toxic and eco-friendly methods. This study presents a novel and highly efficient Ag NPs-modified bentonite adsorbent for removing chloride ion, a common environmental pollutant, from drinking water using a facile approach. The surface chemical properties and morphology of the pristine Na-bentonite and Ag NPs-Modified bentonite were characterized by field emission scanning electron microscopy (FESEM) and X-ray spectroscopy (EDX), X-Ray diffraction (XRD), Fourier transform infrared (FTIR), and zeta potential (ζ). To achieve maximum chloride ion removal, the effects of experimental parameters, including adsorbent dosage (1-9 g/L), chloride ion concentration (100-900 mg/L), and reaction time (5-25 h), were examined using the Response Surface Methodology (RSM). The chloride ion removal of 90% was obtained at optimum conditions (adsorbent dosage: 7 g/L, chloride ion concentration: 500 mg/L, and reaction time: 20 h). The adsorption isotherm and kinetics results indicated that the Langmuir isotherm model and pseudo-second-order kinetics were found suitable to chloride ion removal. Additionally, the regeneration and reusability of the Ag NPs-modified bentonite were further studied. In the regeneration and reusability study, the Ag NPs-modified bentonite has shown consistently ≥90% and ≥87% chloride ion removal even up to 2 repeated cycles, separately. Thus, the findings in this study provided convincing evidence for using Ag-NPs modified bentonite as a high-efficiency and promising adsorbent to remove chloride ion from drinking water.

Chitosan-Glycolic Acid Gel Modification of Chloride Ion Transport in Mammalian Skin: An In Vitro Study.

Chitosan, a polyaminosaccharide with high medical and cosmetic potential, can be combined with the beneficial properties of glycolic acid to form a gel that not only moisturizes the skin, but also has a regenerative effect. Its involvement in the activation of biochemical processes may be associated with the activity of skin ion channels. Therefore, the aim of the research was to evaluate the immediate (15 s) and long-term (24 h) effect of chitosan-glycolic acid gel (CGG) on the transepithelial electric potential and the transepithelial electric resistance (R) of skin specimens tested in vitro. Stimulation during immediate and prolonged application of CGG to skin specimens resulted in a significant decrease in the measured minimal transepithelial electric potential (PDmin). The absence of any change in the R after the CGG application indicates that it does not affect the skin transmission, or cause distortion, microdamage or changes in ion permeability. However, the reduction in potential may be due to the increased transport of chloride ions, and thus water, from outside the cell into the cell interior. Increased secretion of chloride ions is achieved by stimulating the action of the CFTR (cystic fibrosis transmembrane conductance). It can be assumed that chitosan gently stimulates the secretion of chlorides, while maintaining a tendency to reduce the transport of sodium ions, without causing deformation or tissue damage.

Correlating genotype with phenotype using CFTR-mediated whole-cell Cl- currents in human nasal epithelial cells.

Dysfunction of the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes a wide spectrum of disease, including cystic fibrosis (CF) and CFTR-related diseases (CFTR-RDs). Here, we investigate genotype-phenotype-CFTR function relationships using human nasal epithelial (hNE) cells from a small cohort of non-CF subjects and individuals with CF and CFTR-RDs and genotypes associated with either residual or minimal CFTR function using electrophysiological techniques. Collected hNE cells were either studied directly with the whole-cell patch-clamp technique or grown as primary cultures at an air-liquid interface after conditional reprogramming. The properties of cAMP-activated whole-cell Cl- currents in freshly isolated hNE cells identified them as CFTR-mediated. Their magnitude varied between hNE cells from individuals within the same genotype and decreased in the rank order: non-CF > CFTR residual function > CFTR minimal function. CFTR-mediated whole-cell Cl- currents in hNE cells isolated from fully differentiated primary cultures were identical to those in freshly isolated hNE cells in both magnitude and behaviour, demonstrating that conditional reprogramming culture is without effect on CFTR expression and function. For the cohort of subjects studied, CFTR-mediated whole-cell Cl- currents in hNE cells correlated well with CFTR-mediated transepithelial Cl- currents measured in vitro with the Ussing chamber technique, but not with those determined in vivo with the nasal potential difference assay. Nevertheless, they did correlate with the sweat Cl- concentration of study subjects. Thus, this study highlights the complexity of genotype-phenotype-CFTR function relationships, but emphasises the value of conditionally reprogrammed hNE cells in CFTR research and therapeutic testing. KEY POINTS: The genetic disease cystic fibrosis is caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel, which controls anion flow across epithelia lining ducts and tubes in the body. This study investigated CFTR function in nasal epithelial cells from people with cystic fibrosis and CFTR variants with a range of disease severity. CFTR function varied widely in nasal epithelial cells depending on the identity of CFTR variants, but was unaffected by conditional reprogramming culture, a cell culture technique used to grow large numbers of patient-derived cells. Assessment of CFTR function in vitro in nasal epithelial cells and epithelia, and in vivo in the nasal epithelium and sweat gland highlights the complexity of genotype-phenotype-CFTR function relationships.

Case report: Salicylate intoxication can present with a normal anion gap metabolic acidosis depending on method used for measuring chloride.

Severe salicylate intoxication usually presents with a high anion gap metabolic acidosis. We describe a patient with severe salicylate intoxication who presented with a surprisingly normal anion gap metabolic acidosis. Initial salicylate level was 594 mg/L (therapeutic range 50-300 mg/L). In this case, the anion gap was normal due to a falsely elevated chloride concentration measured using a direct ion-selective electrode (ISE; ABL90-flex). Since earlier case reports have shown that salicylate ions can interfere with chloride measurement using different ISEs, available samples were reanalysed using an indirect ISE (Roche Cobas 8000), in which salicylate levels up to 1000 mg/L were found to cause no significant interference. With this method, chloride concentration was found to be 115 instead of 122 mmol/L, leading to the expected elevated anion gap. We performed a spike experiment to investigate the impact of different salicylate levels and bicarbonate concentrations on the measured chloride concentration for both methods. This experiment showed that the difference between chloride concentrations was mainly explained by interference with bicarbonate. It is important for clinicians to be aware of this possible interference, since a high anion gap metabolic acidosis can be a clue to suspect salicylate poisoning and early recognition and appropriate treatment is important. The patient was successfully treated with haemodialysis and no rebound toxicity was observed.

Chloride Ion Adsorption Enables Ampere-Level CO2 Electroreduction over Silver Hollow Fiber.

Electrochemical conversion of CO2 into valuable feedstocks is a promising strategy for carbon neutrality. However, it remains a challenge to possess a large current density, a high faradaic efficiency and excellent stability for practical applications of CO2 utilization. Herein, we report a facile tactic that enables exceedingly efficient CO2 electroreduction to CO by virtue of low-coordination chloride ion (Cl- ) adsorption on a silver hollow fiber (Ag HF) electrode. A CO faradaic efficiency of 92.3 % at a current density of one ampere per square centimeter (1 A cm-2 ) in 3.0 M KCl with a sustained performance observed during a 150-hour test was achieved, which is better than state-of-the-art electrocatalysts. The electrochemical results and density functional theory (DFT) calculations suggested a low-coordination Cl- adsorption on surface of Ag HF, which not only suppressed the competitive hydrogen evolution reaction (HER), but also facilitated the CO2 reduction kinetics.

The intracellular chloride channel 4 (CLIC4) activates systemic sclerosis fibroblasts.

OBJECTIVES: Tissue fibrosis in SSc is driven by active fibroblasts (myofibroblasts). Previous studies have shown the intracellular chloride channel 4 (CLIC4) mediates the activation of cancer-associated fibroblasts. In this study we investigated the role of CLIC4 in SSc fibroblast activation. METHODS: Fibroblasts were obtained from full thickness skin biopsies from SSc patients (early-diffuse). RNA and protein were collected from the fibroblasts and CLIC4 transcript and protein levels were assessed by qPCR and western blot. SSc patient fibroblasts were treated with the chloride channel inhibitors nitro-2-(3-phenylpropylamino)benzoic acid and indyanyloxyacetic acid 94. RESULTS: CLIC4 was expressed at significantly higher levels in SSc patients' fibroblasts compared with healthy controls, at both the transcript (3.7-fold) and protein (1.7-fold) levels. Inhibition of the TGF-ß receptor and its downstream transcription factor SMAD3 led to a reduction in CLIC4 expression, confirming this pathway as the main driver of CLIC4 expression. Importantly, treatment of SSc fibroblasts with known pharmacological inhibitors of CLIC4 led to reduced expression of the myofibroblast markers collagen type 1 and α-smooth muscle actin, inferring a direct role for CLIC4 in disease pathogenesis. CONCLUSIONS: We have identified a novel role for CLIC4 in SSc myofibroblast activation, which strengthens the similarities of SSc fibroblasts with cancer-associated fibroblasts and highlights this channel as a novel target for therapeutic intervention.

A mini-review on ion fluxes that regulate NLRP3 inflammasome activation.

The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome can be induced by a wide spectrum of activators. This is unlikely achieved by the binding of different activators directly to the NLRP3 protein itself, as the activators found so far show different forms of chemical structures. Previous studies have shown that these activators can induce potassium ion (K+) and chloride ion (Cl-) efflux, calcium (Ca2+) and other ion mobilization, mitochondrial dysfunction, and lysosomal disruption, all of which are believed to cause NLRP3 inflammasome activation; how these events are induced by the activators and how they coordinate with each other in inducing the NLRP3 inflammasome activation are not fully understood. Increasing evidence suggests that the coordinated change of intracellular ion concentrations may be a common mechanism for the NLRP3 activation by different activators. In this mini-review, we present a brief summary of the current knowledge about how different ionic flows (including K+, sodium ion, Ca2+, magnesium ion, manganese ion, zinc ion, iron ion, and Cl-) are involved in regulating the NLRP3 inflammasome activation in macrophages.

Self-Assembly of Size-Controlled m-Pyridine-Urea Oligomers and Their Biomimetic Chloride Ion Channels.

The m-pyridine urea (mPU) oligomer was constructed by using the intramolecular hydrogen bond formed by the pyridine nitrogen atom and the NH of urea and the intermolecular hydrogen bond of the terminal carbonyl group and the NH of urea. Due to the synergistic effect of hydrogen bonds, mPU oligomer folds and exhibits strong self-assembly behaviour. Affected by folding, mPU oligomer generates a twisted plane, and one of its important features is that the carbonyl group of the urea group orientates outwards from the twisted plane, while the NHs tend to direct inward. This feature is beneficial to NH attraction for electron-rich species. Among them, the trimer self-assembles into helical nanotubes, and can efficiently transport chloride ions. This study provides a novel and efficient strategy for constructing self-assembled biomimetic materials for electron-rich species transmission.

Carbon monoxide-releasing molecules inhibit the cystic fibrosis transmembrane conductance regulator Cl- channel.

The gasotransmitter carbon monoxide (CO) regulates fluid and electrolyte movements across epithelial tissues. However, its action on anion channels is incompletely understood. Here, we investigate the direct action of CO on the cystic fibrosis transmembrane conductance regulator (CFTR) by applying CO-releasing molecules (CO-RMs) to the intracellular side of excised inside-out membrane patches from cells heterologously expressing wild-type human CFTR. Addition of increasing concentrations of tricarbonyldichlororuthenium(II) dimer (CORM-2) (1-300 µM) inhibited CFTR channel activity, whereas the control RuCl3 (100 µM) was without effect. CORM-2 predominantly inhibited CFTR by decreasing the frequency of channel openings and, hence, open probability (Po). But, it also reduced current flow through open channels with very fast kinetics, particularly at elevated concentrations. By contrast, the chemically distinct CO-releasing molecule CORM-3 inhibited CFTR by decreasing Po without altering current flow through open channels. Neither depolarizing the membrane voltage nor raising the ATP concentration on the intracellular side of the membrane affected CFTR inhibition by CORM-2. Interestingly, CFTR inhibition by CORM-2, but not by CFTRinh-172, was prevented by prior enhancement of channel activity by the clinically approved CFTR potentiator ivacaftor. Similarly, when added after CORM-2, ivacaftor completely relieved CFTR inhibition. In conclusion, CORM-2 has complex effects on wild-type human CFTR consistent with allosteric inhibition and open-channel blockade. Inhibition of CFTR by CO-releasing molecules suggests that CO regulates CFTR activity and that the gasotransmitter has tissue-specific effects on epithelial ion transport. The action of ivacaftor on CFTR Cl- channels inhibited by CO potentially expands the drug's clinical utility.

Characterization of Fe5(AsO3)3Cl2(OH)4·5H2O, a new ferric arsenite hydroxychloride precipitated from FeCl3-As2O3-HCl solutions relevant to arsenic immobilization.

Tooeleite (Fe6(AsO3)4SO4(OH)4·4H2O) is widely precipitated for direct As(III) removal from sulfate-rich industrial effluents. However, whether or not Fe(III)-As(III)-Cl(-I) precipitate is produced in chloridizing leaching media for As immobilization is almost unknown. This work founded the existence of ferric arsenite (hydroxy)chloride as a new mineral for As(III) removal. Its chemical composition and solid characterization were subsequently studied by using scanning electron microscope with an energy dispersive spectrometer (SEM-EDS), X-ray diffraction (XRD), infrared (FT-IR), Raman spectroscopy and thermogravimetric (TG) curve. The results showed the formation of a yellow precipitate after 3-days reaction of Fe(III)/As(III) with molar ratio ≈ 1.7 in chloride solution at pH 2.3 neutralized with NaOH. Compared with tooeleite, chemical analysis and solid characterization indicated that Cl(-I) replaces SO4(-II) producing ferric arsenite hydroxychloride with formula Fe5(AsO3)3Cl2(OH)4·5H2O. This new plate shaped solid showed better crytallinity than tooeleite, although it has similar morphology and characteristic bands to tooeleite. The FT-IR bands at 628, 964 cm-1 and the Raman bands at 448, 610, 961 cm-1 were assigned to Fe-O or As(III)-O-Fe or As(III)-O bending/stretching vibration, indicating that both arsenite and chloride substituted for the position of sulfate for ferric arsenite hydroxychloride produced due to the lack of the SO42- vibrations. Cl-(I) also contributed to increase As removal efficiency in aqueous sulfate media under acidic pH conditions via the probable formation of sulfate-chloride ferric arsenite.