Extracellular acidification, playing a promoting role in the process of acute pancreatitis, has been reported to activate Cl− channels in several types of cells. However, whether extracellular ...acidification aggravates acute pancreatitis via activating Cl− channels remains unclear. Here, we investigated the effects of extracellular acidification on Cl− channels in rat pancreatic acinar AR42J cells using whole-cell patch-clamp recordings. We found that extracellular acidification induced a moderately outward-rectified Cl− current, with a selectivity sequence of I− > Br− ≥ Cl− > gluconate−, while intracellular acidification failed to induce the currents. The acid-sensitive currents were inhibited by Cl− channel blockers, 4,4′-Diisothiocyanatostilbene-2,2′-disulfonic acid disodium salt hydrate and 5-Nitro-2-(3-phenylpropylamino) benzoic acid. After ClC-3 was silenced by ClC-3 shRNA, the acid-sensitive Cl− currents were attenuated significantly, indicating that ClC-3 plays a vital role in the induction of acid-sensitive Cl− currents. Extracellular acid elevated the intracellular level of reactive oxygen species (ROS) significantly, prior to inducing Cl− currents. When ROS production was scavenged, the acid-sensitive Cl− currents were abolished. Whereas, the level of acid-induced ROS was unaffected with silence of ClC-3. Our findings above demonstrate that extracellular acidification induces a Cl− current in pancreatic acinar cells via promoting ROS generation, implying an underlying mechanism that extracellular acidification might aggravate acute pancreatitis through Cl− channels.
•A chloride channel in AR42J cells was sensitive to extracellular acidification.•ClC-3 played a vital role in the induction of the acid-sensitive Cl− currents.•Reactive oxygen species involved in inducing the acid-sensitive Cl− currents.
Nitrobenzenesulfochlorination of β-aminopropioamidoximes leads to a set of products depending on the structure of the initial interacting substances and reaction conditions. Amidoximes, ...functionalized at the terminal C atom with six-membered
-heterocycles (piperidine, morpholine, thiomorpholine and phenylpiperazine), as a result of the spontaneous intramolecular heterocyclization of the intermediate reaction product of an S
2 substitution of a hydrogen atom in the oxime group of the amidoxime fragment by a nitrobenzenesulfonyl group, produce spiropyrazolinium
or
-nitrobenzenesulfonates. An exception is
-nitrobenzenesulfochlorination of β-(thiomorpholin-1-yl)propioamidoxime, which is regioselective at room temperature, producing two spiropyrazolinium salts (
-nitrobezenesulfonate and chloride), and regiospecific at the boiling point of the solvent, when only chloride is formed. The
-Nitrobezenesulfochlorination of β-(benzimidazol-1-yl)propioamidoxime, due to the reduced nucleophilicity of the aromatic β-amine nitrogen atom, is regiospecific at both temperatures, and produces the
-
-nitrobenzenesulfochlorination product. The antidiabetic screening of the new nitrobezenesulfochlorination amidoximes found promising samples with in vitro α-glucosidase activity higher than the reference drug acarbose.
H-NMR spectroscopy and X-ray analysis revealed the slow inversion of six-membered heterocycles, and experimentally confirmed the presence of an unfavorable stereoisomer with an axial N-N bond in the pyrazolinium heterocycle.
Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are ...chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs have a serine. The LeuT-E290S mutant displays chloride-dependent activity. We show that, in LeuT-E290S cocrystallized with bromide or chloride, the anion is coordinated by side chain hydroxyls from Tyr47, Ser290, and Thr254 and the side chain amide of Gln250. The bound anion and the nearby sodium ion in the Na1 site organize a connection between their coordinating residues and the extracellular gate of LeuT through a continuous H-bond network. The specific insights from the structures, combined with results from substrate binding studies and molecular dynamics simulations, reveal an anion-dependent occlusion mechanism for NSS and shed light on the functional role of chloride binding.
The anion exchanger Pendrin, which is encoded by SLC26A4 (human)/Slc26a4 (mouse) gene, is localized on the apical membrane of non-acid-secreting intercalated (IC) cells in the kidney cortical ...collecting duct (CCD). To examine its role in the mediation of bicarbonate secretion in vivo and the apical Cl(-)/HCO(3)(-) exchanger in the kidney CCD, mice with genetic deletion of pendrin were generated. The mutant mice show the complete absence of pendrin expression in their kidneys as assessed by Northern blot hybridization, Western blot, and immunofluorescence labeling. Pendrin knockout (KO) mice display significantly acidic urine at baseline pH 5.20 in KO vs. 6.01 in wild type (WT); P < 0.0001 along with elevated serum HCO(3)(-) concentration (27.4 vs. 24 meq/l in KO vs. WT, respectively; P < 0.02), consistent with decreased bicarbonate secretion in vivo. The urine chloride excretion was comparable in WT and KO mice. For functional studies, CCDs were microperfused and IC cells were identified by their ability to trap the pH fluorescent dye BCECF. The apical Cl(-)/HCO(3)(-) exchanger activity in B-IC and non-A, non-B-IC cells, as assessed by intracellular pH monitoring, was significantly reduced in pendrin-null mice. The basolateral Cl(-)/HCO(3)(-) exchanger activity in A-IC cells and in non-A, non-B-IC cells, was not different in pendrin KO mice relative to WT animals. Urine NH(4)(+) (ammonium) excretion increased significantly, consistent with increased trapping of NH(3) in the collecting duct in pendrin KO mice. We conclude that Slc26a4 (pendrin) deletion impairs the secretion of bicarbonate in vivo and reduces apical Cl(-)/HCO(3)(-) exchanger activity in B-IC and non-A, non-B-IC cells in CCD. Additional apical Cl(-)/HCO(3)(-) exchanger(s) is (are) present in the CCD.
A highly regio- and stereoselective hydrochlorination/cyclization of enynes has been reported by FeCl
catalysis. A variety of enynes undergo this cyclization transformation with acetic chloride as ...the chlorine source and H
O providing protons via a cationic pathway. This protocol provides a cheap, simple, stereospecific, and effective cyclization to afford heterocyclic alkenyl chloride compounds as
isomers with high yields (≤98%) and regioselectivity.
A simple and practical method of fluoroalkylthiolation using fluoroalkylsulfonyl chlorides (RfSO2Cl, Rf=CF3, C4F9, C8F17, CF2H and CH2CF3) has been developed. These easy‐to‐handle reagents are ...powerful and can be used for electrophilic fluoroalkylthiolation of electron‐rich arenes and thiols using diethyl phosphite as reducing agent.
Biochemical systems are adaptable, capable of reconstitution at all levels to achieve the functions associated with life. Synthetic chemical systems are more limited in their ability to reorganize to ...achieve new functions; they can reconfigure to bind an added substrate (template effect) or one binding event may modulate a receptor's affinity for a second substrate (allosteric effect). Here we describe a synthetic chemical system that is capable of structural reconstitution on receipt of one anionic signal (perchlorate) to create a tight binding pocket for another anion (chloride). The complex, barrel-like structure of the chloride receptor is templated by five perchlorate anions. This second-order templation phenomenon allows chemical networks to be envisaged that express more complex responses to chemical signals than is currently feasible.
Abstract
The development of energy-dense all-solid-state Li-based batteries requires positive electrode active materials that are ionic conductive and compressible at room temperature. Indeed, these ...material properties could contribute to a sensible reduction of the amount of the solid-state electrolyte in the composite electrode, thus, enabling higher mass loading of active materials. Here, we propose the synthesis and use of lithium titanium chloride (Li
3
TiCl
6
) as room-temperature ionic conductive (i.e., 1.04 mS cm
−1
at 25 °C) and compressible active materials for all-solid-state Li-based batteries. When a composite positive electrode comprising 95 wt.% of Li
3
TiCl
6
is tested in combination with a Li-In alloy negative electrode and Li
6
PS
5
Cl/Li
2
ZrCl
6
solid-state electrolytes, an initial discharge capacity of about 90 mAh g
−1
and an average cell discharge voltage of about 2.53 V are obtained. Furthermore, a capacity retention of more than 62% is attainable after 2500 cycles at 92.5 mA g
−1
and 25 °C with an applied external pressure of 1.5 tons. We also report the assembly and testing of a “single Li
3
TiCl
6
” cell where this chloride material is used as the solid electrolyte, negative electrode and positive electrode.
In this study, we report the anomalous enhancement of specific heat capacity of high-temperature nanofluids. Alkali metal chloride salt eutectics were doped with silica nanoparticles at 1% mass ...concentration. The specific heat capacity of the nanofluid was enhanced by 14.5%. Dispersion behavior of the nanoparticles in the eutectic was confirmed by scanning electron microscopy (SEM). Three independent competing transport mechanisms are enumerated to explain this anomalous behavior.
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