Apical Water Research Articles

Synthesis, crystal structure, Hirshfeld surface, and DFT studies of a Copper(II) complex of 5,5′-dimethyl-2,2′-bipyridine and 1,2,2-trimethylcyclopentane-1,3-dicarboxylic acid

A new metal-organic hybrid complex [Cu(5,5′-dmbipy) (D-cam) (H2O)]n (1), (5,5′-dmbipy = 5,5′-dimethyl-2,2′-bipyridine, D-cam = D-camphoric acid anion) was hydrothermally synthesized. This complex was characterized by FTIR spectroscopy, TGA, and single-crystal X-ray diffraction. Crystallographic studies show that the title complex 1 crystallizes in an orthorhombic system with a P212121 space group with a = 06.9518(05) Ǻ, b = 13.5516(13) Ǻ, c = 22.6380(02)Ǻ; V = 2132.7(3) Ǻ3. The title CuII complex adopts a square pyramidal configuration. DFT study and Hirshfeld topology analysis of complex 1 was also done. The crystal achieves its three-dimensional structure and stability through polymeric chains having helical motifs of arrangement in between moieties and interconnected through hydrogen bonding interactions between the apical water molecule and non-coordinated oxygen atoms of the D-cam2- ligands. TGA, DFT calculations and Hirshfeld topology analysis revealed that the title complex 1 was stable.

Structure and Population of Complex Ionic Species in FeCl2 Aqueous Solution by X-ray Absorption Spectroscopy.

Technologies for mass production require cheap and abundant materials such as ferrous chloride (FeCl2). The literature survey shows the lack of experimental studies to validate theoretical conclusions related to the population of ionic Fe-species in the aqueous FeCl2 solution. Here, we present an in situ X-ray absorption study of the structure of the ionic species in the FeCl2 aqueous solution at different concentrations (1–4 molL−1) and temperatures (25–80 °C). We found that at low temperature and low FeCl2 concentration, the octahedral first coordination sphere around Fe is occupied by one Cl ion at a distance of 2.33 (±0.02) Å and five water molecules at a distance of 2.095 (±0.005) Å. The structure of the ionic complex gradually changes with an increase in temperature and/or concentration. The apical water molecule is substituted by a chlorine ion to yield a neutral Fe[Cl2(H2O)4]0. The observed substitutional mechanism is facilitated by the presence of the intramolecular hydrogen bonds as well as entropic reasons. The transition from the single charged Fe[Cl(H2O)5]+ to the neutral Fe[Cl2(H2O)4]0 causes a significant drop in the solution conductivity, which well correlates with the existing conductivity models.

Quasi-Isostructural Co(II) and Ni(II) Complexes with Mefenamato Ligand: Synthesis, Characterization, and Biological Activity.

Three metal complexes of mefenamato ligand 1 were synthesized: [Co2(mef)4(EtOH)2(H2O)4]: 2; [Co(mef)2(MeOH)4]∙2MeOH: 3; and [Ni(mef)2(MeOH)4]∙2MeOH: 4. Their compositions and properties were investigated by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Crystal structures were determined by the single crystal X-ray diffraction technique. Additionally, their antioxidant and antimicrobial activity were established, thus proving good/moderate bioactivity against Gram-positive bacteria and yeasts. In the crystal structure of 2, an apical water molecule is shared between two adjacent cobalt(II) ions, resulting in the formation of a polymeric chain extending along the [100] direction. Meanwhile, structures 3 and 4 have strong intermolecular hydrogen bonds with diverse topologies that yield unique quasi-isostructural arrangements. The packing topology is reflected by the Hirshfeld surface analysis of intermolecular contacts.

Diaquatetra-kis(μ-3-meth-oxy-benzoato-κ2 O 1:O 1')dicopper(II).

The asymmetric unit of the binuclear title compound, [Cu2(C8H7O3)4(H2O)2], comprises two halves of diaquatetra-kis-(μ-3-meth-oxy-benzoato-κ2 O 1:O 1')dicopper(II) units. The paddle-wheel structure of each complex is completed by application of inversion symmetry, with the inversion centre situated at the midpoint between two CuII atoms in each dimer. The two CuII atoms of each centrosymmetric dimer are bridged by four 3-meth-oxy-benzoate anions resulting in Cu⋯Cu separations of 2.5961 (11) and 2.6060 (12) Å, respectively. The square-pyramidal coordination sphere of each CuII atom is completed by an apical water mol-ecule. Inter-molecular O-H⋯O hydrogen bonds of weak nature link the complexes into layers parallel to (100). The three-dimensional network structure is accomplished by C-H⋯O hydrogen bonds inter-linking adjacent layers.

Does lysine acetylation affect water permeability of the collecting duct?

We recently reported that there are > 400 proteins in the inner medullary collecting duct that are post‐translationally lysine acetylated (ac‐K). Although historically, ac‐K proteins were thought to be predominantly histone proteins in the nucleus, we now know that all cellular compartments are enriched with ac‐K proteins. Pathway analyses determined that ac‐K proteins are enriched in various physiological processes such as glycolysis and vasopressin‐mediated water reabsorption. We recently identified the basolateral water channel, aquaporin‐3 (AQP3), as undergoing lysine acetylation (AQP3 K282). Thus, the purpose of this study was to determine if ac‐K AQP3 affects water permeability. We developed antibodies to specifically detected ac‐K AQP3 or total AQP3. In both male and female mice, ac‐K AQP3 was expressed in the basolateral membrane of the cortical and outer medullary collecting duct. However, following 24 h of water deprivation, ac‐K AQP3 was also found in the inner medullary collecting duct. Next, we developed AQP3 K point mutation plasmids, with K282Q representing an acetylated mimic, and K282 representing a deacetylated mimic. These constructs were stably expressed in vasopressin‐responsive mouse cortical collecting duct cells (AQP3mpkCCDs). Using the cell volume sensitive dye, calcein, water permeability of these mutant cells was determined following an osmotic stimulus. We found the acetylated mimic (K282Q) had the highest water permeability followed by the AQP3 wild type K282 cells and the deacetylated mimic (K282R). Finally, using CRISPR/CAS we engineered whole body point mutation mice. The K282Q mutant mice and littermate controls (K282) all developed normally. As adults, K282Q mice presented with elevated plasma osmolality (307 ± 2 mOsm/Kg H2O vs 298 ± 4 mOsm/kg H2O, P = 0.04) at baseline. Following 3 days of hydration with 5% sucrose water, K282Q produced twice as much urine as controls during their active period (2.16 ± 0.5 ml/12h vs 0.88 ± 0.2, P = 0.03). Moreover, when challenged with a 2 ml sterile water i.p., K282Q mice excreted majority of the water load within the first 3 h, while controls reached peak urine flow after 3 h. Finally, we quantified AQP2 (the apical water channel) and AQP3 mRNA expression and protein abundance. AQP2, AQP3 and AQP4 mRNA expression was similar between control and mutant mice. Surprisingly, K282Q mutant mice presented with significantly less AQP2 and AQP3 protein abundance compared to controls. Thus, mutating K282 in vivo resulted in a loss of AQP3 (a potentially AQP2) stability, and highlights the importance of this lysine residue. To conclude, lysine acetylation of AQP3 is a novel posttranslational modification that may regulate AQP function and water permeability in the collecting duct.Support or Funding InformationK01DK105038, R03DK120503, the University of Alabama at Birmingham Pittman Scholarship, NIH P30 DK074038

A supramolecular polymeric chain in the cobalt(II) complex with diclofenac: synthesis, crystal structure, spectroscopic, thermal and antioxidant activity

A cobalt(II) complex with empirical formula [Co(dicl)2·(H2O)3]·MeOH (where dicl = diclofenac) was synthesized and characterized by elemental analysis, flame atomic absorption spectroscopy (FAAS), infrared spectroscopy (FTIR) and thermal decomposition techniques (TGA). The crystal structure of the complex was determined by single crystal X-ray diffraction technique. The compound crystallizes in the monoclinic space group I2/a. Apical water molecules link adjacent cobalt(II) ions forming polymeric chains along the crystal a axis. The thermal behavior of the complex was studied by TG/DTG/DTA, TG/MS and TG/FTIR methods under non-isothermal conditions in air. Upon heating [Co(dicl)2·(H2O)3]·MeOH decomposes progressively to metal oxides, which are the final products of pyrolysis. Furthermore, antioxidant activity of the complex was examined.

A physiologically-motivated model of cystic fibrosis liquid and solute transport dynamics across primary human nasal epithelia.

Cystic fibrosis (CF) disease is caused by mutations affecting the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel expressed in the mucosal side of epithelial tissue. In the airway, dysfunctional CFTR results in a transepithelial osmotic imbalance leading to hyperabsorption of airway surface liquid mucostasis, chronic inflammation, and eventual respiratory failure. Human nasal epithelial cell cultures from healthy and CF donors were used to perform studies of liquid and solute transport dynamics at an air/liquid interface in order to emulate the in vivo airway. Then, these results were used to inform a quantitative systems pharmacology model of airway epithelium describing electrically and chemically driven transcellular ionic transport, contributions of both convective and diffusive paracellular solute transport, and osmotically driven transepithelial water dynamics. Model predictions showed CF cultures, relative to non-CF ones, have increased apical and basolateral water permeabilities, and increase paracellular permeability and transepithelial chemical driving force for a radiolabeled tracer used to track small molecule absorption. These results provide a computational platform to better understand and probe the mechanisms behind the liquid hyperabsorption and small molecule retention profiles observed in the CF airway.

Solute and water transport along an inner medullary collecting duct undergoing peristaltic contractions.

The mechanism by which solutes accumulate in the inner medulla of the mammalian kidney has remained incompletely understood. That persistent mystery has led to hypotheses based on the peristaltic contractions of the pelvic wall smooth muscles. It has been demonstrated the peristaltic contractions propel fluid down the collecting duct in boluses. In antidiuresis, boluses are sufficiently short that collecting ducts may be collapsed most of the time. In this study, we investigated the mechanism by which about half of the bolus volume is reabsorbed into the collecting duct cells despite the short contact time. To accomplish this, we developed a dynamic mathematical model of solute and water transport along a collecting duct of a rat papilla undergoing peristaltic contractions. The model predicts that, given preexisting axial concentration gradients along the loops of Henle, ∼40% of the bolus volume is reabsorbed as the bolus flows down the inner medullary collecting duct. Additionally, simulation results suggest that while the contraction-induced luminal hydrostatic pressure facilitates water extraction from the bolus, that pressure is not necessary to concentrate the bolus. Also, neither the negative interstitial pressure generated during the relaxation phase nor the concentrating effect of hyaluronic acid has a significant effect on bolus concentration. Taken together, these findings indicate that the high collecting duct apical water permeability allows a substantial amount of water to be extracted from the bolus, despite its short transit time. However, the potential role of the peristaltic waves in the urine-concentrating mechanism remains to be revealed.

Covalency and magnetic anisotropy in lanthanide single molecule magnets: the DyDOTA archetype.

Lanthanide ions when complexed by polyamino-polycarboxylate chelators form a class of compounds of paramount importance in several research and technological areas, particularly in the fields of magnetic resonance and molecular magnetism. Indeed, the gadolinium derivative is one of the most employed contrast agents for magnetic resonance imaging while the dysprosium one belongs to a new generation of contrast agents for T2-weighted MRI. In molecular magnetism, Single Molecule Magnets (SMMs) containing lanthanide ions have become readily popular in the chemistry and physics communities since record energy barriers to the reversal of magnetization were reported. The success of lanthanide complexes lies in their large anisotropy due to the contribution of the unquenched orbital angular momentum. However, only a few efforts have been made so far to understand how the f-orbitals can be influenced by the surrounding ligands. The outcomes have been rationalized using mere electrostatic perturbation models. In the archetype compound [Na{Dy(DOTA) (H2O)}]·4H2O (Na{DyDOTA}·4H2O) an unexpected easy axis of magnetization perpendicular to the pseudo-tetragonal axis of the molecule was found. Interestingly, a dependency of the orientation of the principal magnetization axis on the simple rotation of the coordinating apical water molecule (AWM) - highly relevant for MRI contrast - around the Dy-OAWM bond was predicted by ab initio calculations, too. However, such a behaviour has been contested in a subsequent paper justifying their conclusions on pure electrostatic assumptions. In this paper, we want to shed some light on the nature of the subtle effects induced by the water molecule on the magnetic properties of the DyDOTA archetype complex. Therefore, we have critically reviewed the structural models already published in the literature along with new ones, showing how the easy axis orientation can dangerously depend on the chosen model. The different computed behaviors of the orientation of the easy axis of magnetization have been rationalized as a function of the energy gap between the ground and the first excited doublet. Magneto-structural correlations together with a mapping of the electrostatic potential generated by the ligands around the Dy(iii) ion through a multipolar expansion have also been used to evidence and quantify the covalent contribution of the AWM orbitals.

907 - Deficits in Apical Sodium and Water Transporters Along with Maintenance of CFTR Account for Diarrheal Pathology in MYO5B Ko Mice and Patients with MVID

907 - Deficits in Apical Sodium and Water Transporters Along with Maintenance of CFTR Account for Diarrheal Pathology in MYO5B Ko Mice and Patients with MVID

Polyethylenimine-mediated expression of transgenes in the acinar cells of rats salivary glands in vivo.

Non viral-mediated transfection of plasmid DNA provides a fast and reliable way to express various transgenes in selected cell populations in live animals. Here, we show an improvement of a previously published method that is based on injecting plasmid DNA into the ductal system of the salivary glands in live rats. Specifically, using complexes between plasmid DNA and polyethyleneimine (PEI) we show that the expression of the transgenes is directed selectively to the salivary acinar cells. PEI does not affect the ability of cells to undergo regulated exocytosis, which was one of the main drawbacks of the previous methods. Moreover PEI does not affect the proper localization and targeting of transfected proteins, as shown for the apical plasma membrane water channel aquaporin 5 (AQP5). Overall, this approach, coupled with the use of intravital microscopy, permits to conduct localization and functional studies under physiological conditions, in a rapid, reliable, and affordable fashion.

Syntheses, X-ray crystal structures and spectroscopic characterization of rare μ-di-σ pyrazole based bridging keto carbonyl complexes derived from Cd(II) salts

The pyrazole based ligands (E)-2-(3,5-dimethyl-1H-pyrazol-1-yl)-N′-(pyridin-2-ylmethylene acetohydrazide (N-PzOPyH) and (E)-5-methyl-N′-(pyridin-2-ylmethylene)-1H-pyrazole-3-carbo hydrazide (PzOPyH), a 1:1 condensation product of 2-(3,5-dimethyl-1H-pyrazol-1-yl)aceto hydrazide and 5-methylpyrazole-3-carbohydrazide with pyridine-2-carbaldehyde respectively, and their keto oxygen bridged Cd(II) complexes [Cd2(N-PzOPy)2(H2O)4](ClO4)4 (1), [Cd2(PzOPy)2(H2O)4](ClO4)4 (2) and [Cd2(PzOPy)2(NO3)4] (3)] are reported. They have been characterized structurally and spectroscopically. The potential tetradentate NONN-donor ligands N-PzOPyH and PzOPyH are engaged in the coordination around the cadmium(II) center through the nitrogen atoms of pyrazole, azomethine and pyridine and the ketonic oxygen atom of the carbohydrazide group to form complexes 1, 2 and 3, respectively. These ligands span themselves in the equatorial plane and the pentagonal bipyramidal geometry is completed around the metal centres (with an N3O4 chromophore) with two apical water molecules (for 1 and 2) and with two nitrate ions (for 3). These keto bridged Cd(II) complexes are further stabilised by supramolecular interactions, like π⋯π, C–H⋯π and H-bonding interactions.

Crystal structure of magnesium selenate hepta-hydrate, MgSeO4·7H2O, from neutron time-of-flight data.

MgSeO4·7H2O is isostructural with the analogous sulfate, MgSO4·7H2O, consisting of isolated [Mg(H2O)6](2+) octa-hedra and [SeO4](2-) tetra-hedra, linked by O-H⋯O hydrogen bonds, with a single inter-stitial lattice water mol-ecule. As in the sulfate, the [Mg(H2O)6](2+) coordination octa-hedron is elongated along one axis due to the tetra-hedral coordination of the two apical water mol-ecules; these have Mg-O distances of ∼2.10 Å, whereas the remaining four trigonally coordinated water mol-ecules have Mg-O distances of ∼2.05 Å. The mean Se-O bond length is 1.641 Å and is in excellent agreement with other selenates. The unit-cell volume of MgSeO4·7H2O at 10 K is 4.1% larger than that of the sulfate at 2 K, although this is not uniform; the greater part of the expansion is along the a axis of the crystal.

The calcium-activated chloride channel Anoctamin 1 contributes to the regulation of renal function

The role of calcium-activated chloride channels for renal function is unknown. By immunohistochemistry we demonstrate dominant expression of the recently identified calcium-activated chloride channels, Anoctamin 1 (Ano1, TMEM16A) in human and mouse proximal tubular epithelial (PTE) cells, with some expression in podocytes and other tubular segments. Ano1-null mice had proteinuria and numerous large reabsorption vesicles in PTE cells. Selective knockout of Ano1 in podocytes (Ano1-/-/Nphs2-Cre) did not impair renal function, whereas tubular knockout in Ano1-/-/Ksp-Cre mice increased urine protein excretion and decreased urine electrolyte concentrations. Purinergic stimulation activated calcium-dependent chloride currents in isolated proximal tubule epithelial cells from wild-type but not from Ano1-/-/Ksp-Cre mice. Ano1 currents were activated by acidic pH, suggesting parallel stimulation of Ano1 chloride secretion with activation of the proton-ATPase. Lack of calcium-dependent chloride secretion in cells from Ano1-/-/Ksp-Cre mice was paralleled by attenuated proton secretion and reduced endosomal acidification, which compromised proximal tubular albumin uptake. Tubular knockout of Ano1 enhanced serum renin and aldosterone concentrations, probably leading to enhanced compensatory distal tubular reabsorption, thus maintaining normal blood pressure levels. Thus, Ano1 has a role in proximal tubular proton secretion and protein reabsorption. The results correspond to regulation of the proton-ATPase by the Ano1-homolog Ist2 in yeast.

Elevated cAMP increases aquaporin-3 plasma membrane diffusion

Regulated urine concentration takes place in the renal collecting duct upon arginine vasopressin (AVP) stimulation, where subapical vesicles containing aquaporin-2 (AQP2) are inserted into the apical membrane instantly increasing water reabsorption and urine concentration. The reabsorped water exits via basolateral AQP3 and AQP4. Upon long-term stimulation with AVP or during thirst, expression levels of both AQP2 and AQP3 are increased; however, there is so far no evidence for short-term AVP regulation of AQP3 or AQP4. To facilitate the increase in transepithelial water transport, AQP3 may be short-term regulated via changes in protein-protein interactions, incorporation into lipid rafts, and/or changes in steady-state turnover, which could result in changes in the diffusion behavior of AQP3. Thus we measured AQP3 diffusion coefficients upon stimulation with the AVP mimic forskolin to reveal if AQP3 could be short-term regulated by AVP. k-Space image correlation spectroscopy (kICS) analysis of time-lapse image sequences of basolateral enhanced green fluorescent protein-tagged AQP3 (AQP3-EGFP) revealed that the forskolin-mediated elevation of cAMP increased the diffusion coefficient by 58% from 0.0147 ± 0.0082 μm(2)/s (control) to 0.0232 ± 0.0085 μm(2)/s (forskolin, P < 0.05). Quantum dot-conjugated antibody labeling also revealed a significant increase in AQP3 diffusion upon forskolin treatment by 44% [0.0104 ± 0.0040 μm(2)/s (control) vs. 0.0150 ± 0.0016 μm(2)/s (forskolin, P < 0.05)]. Immunoelectron microscopy showed no obvious difference in AQP3-EGFP expression levels or localization in the plasma membrane upon forskolin stimulation. Thus AQP3-EGFP diffusion is altered upon increased cAMP, which may correspond to basolateral adaptations in response to the increased apical water readsorption.

A new trinuclear zinc(II) complex and a heptacoordinated mononuclear cadmium(II) complex with a pyrimidine derived Schiff base ligand: Syntheses, crystal structures, photoluminescence and DFT calculations

The new N6 donor hexadentate Schiff base 2,4-bis [2-(pyridine-2-ylmethylidene) hydrazinyl] pyrimidine (L), its trinuclear Zn(II) complex, [Zn3(L)2Cl6] (1) and mononuclear heptacoordinate Cd(II) complex [Cd(L)(H2O)2](ClO4)2 (2) have been synthesised and characterised by crystallographically and spectroscopically. Complex 1 is featured by the triangular arrangement of three zinc atoms where the neighbouring Zn atoms are linked via half portion (N3 chromophore) of the same ligand molecule. In 1, the ligand molecules behave as hexadentate ones (employing both pyrimidine nitrogen atoms as active donor centres) to create the octahedral environment around Zn(II). The central and terminal Zn(II) atom has N6 and N3Cl3 chromophores respectively. In 2 the same ligand (L) behaves as pentadentate one (ignoring one pyrimidine nitrogen in the coordination process) to produce a pentagonal bipyramidal geometry with two apical water molecules. The geometries of both complexes were optimised in the singlet state by DFT method. The TDDFT calculations have been done on the optimised geometries to understand the electronic structure and spectral transition in the complexes. Complex 1 exhibits intraligand 1(π→π*) fluorescence in aqueous methanol solvent at room temperature.

Deuterium Oxide Dilution: A Novel Method to Study Apical Water Layers and Transepithelial Water Transport

Lung epithelia regulate the water flux between gas filled airways and the interstitial compartment in order to maintain organ function. Current methodology to assess transepithelial water transport is limited. We present a D2O dilution method to quantify submicroliter volumes of aqueous solutions on epithelial cell layers. Evaluating D2O/H2O mixtures using mid-infrared (2-25 μm) attenuated total reflection (ATR) spectroscopy, with a resolution of 0.06% vol/vol change, corresponding to 24 nL, was achieved. Using this method, we demonstrate that water transport across NCI-H441 lung epithelial cell layers and apical surface liquid (ASL) volumes are coupled to dexamethasone dependent amiloride-sensitive ion transport. However, contrary to current dogma, electrogenic transport is not rate-limiting for water transport. This clearly indicates the need to directly assess net water rather than ion transport across epithelial cell layers. The presented D2O dilution method enables such direct and quick quantification of transepithelial water transport with high resolution.

Magnetic Anisotropy and Spin‐Parity Effect Along the Series of Lanthanide Complexes with DOTA

Spotting trends: Upon going from Tb(III) to Yb(III) centers in the complexes of the DOTA(4-) ligand, a reorientation of the easy axis of magnetization from perpendicular to parallel to the Ln-O bond of the apical water molecule is experimentally observed and theoretically predicted (SMM=single-molecule magnet). Only ions with an odd number of electrons show slow relaxation of the magnetization.

μ-4,4'-Bipyridine-bis-[aqua-(4-hy-droxy-pyridine-2,6-dicarboxyl-ato)copper(II)

The title compound, [Cu2(C7H3NO5)2(C10H8N2)(H2O)2], exhibits a centrosymmetric binuclear molecule. Each completely deprotonated 4-hy­droxy­pyridine-2,6-dicarb­oxy­lic acid mol­ecule assumes a tridentate chelating coordination mode. The square-pyramidal coordination geometry around the CuII ion is completed by the bridging bipyridine ligand and an apical water molecule. Adjacent complexes are connected via O—H⋯O and C—H⋯O hydrogen bonds to generate a three-dimensional supra­molecular structure.

Magnetic Anisotropy in a Dysprosium/DOTA Single‐Molecule Magnet: Beyond Simple Magneto‐Structural Correlations

Magnetic moments: The orientation of the title single-molecule magnet was investigated by magnetic single crystal and luminescence characterization, supported by ab initio calculations, and was found to be governed by the position of the hydrogen atoms of the apical water molecules. This finding suggests that simple magneto-structural correlations can give misleading clues for research in molecular magnetism as well as in the design of MRI contrast agents. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.