Stereoselective chlorination of methyl β-lactoside with mesyl chloride in N,N-dimethylformamide

Treatment of methyl β-lactoside with mesyl chloride in N,N-dimethylformamide under a variety of conditions gave complex mixtures of chlorinated products, of which nine were isolated and characterised. Chlorination at a secondary position always occurred with inversion of configuration. When the reaction was conducted at 94° for 9 days, a mixture of the 3,3′,4′,6,6′-pentachloride, the 3,3′,6,6′- and 3,4′,6,6′-tetrachlorides, and the 3,6,6′- and 3′,6,6′-trichlorides was obtained together with the 3′,4′-epoxide of the 6,6′-dichloride, which was an artefact. Under milder conditions, the 6,6′-dichloride was encountered, together with methyl 6-chloro-6-deoxy-β-D-glucopyranoside which had arisen by hydrolysis of the interglycosidic bond. It is particularly noteworthy that displacement occurred at C-3′ of the lactoside, in spite of the vic-axial group at C-4′ which should hinder nucleophilic displacement at C-3′. The cause of this anomaly is discussed.     

Genetic toxicology of vinyl chloride—a review

Vinyl chloride (VC) is a colorless gas with a mild, sweet odor. It is extensively used in the production of vinyl chloride polymer, copolymer resin, packaging materials, wire and cable coatings as well as in industrial and laboratory intermediates. It is toxic and also carcinogenic in experimental animals. The wide human exposure to this compound in different industries throughout the world causes great concern for human health. In the present review an attempt has been made to evaluate and update the genotoxic effects of vinyl chloride based on the available literature.     

Comparison of-nitro versus-amino 4, 4′-substituents of disulfonic stilbenes as chloride channel blockers

We showed previously that the disulfonic stilbene DNDS (4, 4-dinitrostilben-2, 2-disulfonic acid) was a potent blocker of outwardly rectifying chloride channels (ORCC). The studies reported here were designed to quantify the relationship between electron withdrawal by the 4, 4-substituents and blocker potency. Specifically we compared the blocking effects and molecular properties of the symmetrically substituted 4, 4-diaminostilben-2, 2-disulfonic acid (DADS) and the hemi-substituted 4-amino, 4-nitrostilben-2, 2-disulfonic acid (ANDS) with those of DNDS. Blockade was studied using outwardly rectifying colonic chloride channels incorporated into planar lipid bilayers. DADS was 430-fold and ANDS 44-fold less potent than DNDS as blockers of ORCC. Amplitude distribution analysis revealed that all three disulfonic stilbenes act as open channel blockers. Furthermore, this kinetic analysis indicated that the lower potency of DADS and ANDS was due to an increase in off rate. These results support the conclusion that the 4, 4-substituents make an important contribution to blockade by stabilizing the channel-blocker complex. Isopotential electron contour maps illustrated the dramatic shift in charge at the 4, 4-poles of the disulfonic stilbene molecule from electronegative in DNDS to electropositive in DADS as well as the bipolar contour of ANDS. Thus, the greater potency of DNDS results from the symmetric electronegative regions at the 4, 4-poles of the molecule. We hypothesize that the channel protein has two corresponding electropositive areas at the blocker binding site.     

The demonstration of chloride ions in the “chloride cells” of the gills of eels (Anguilla anguilla L.) adapted to sea water

Summary The ultrastructure of chloride cells in the gills of eels kept in artificial sea water and of a control animal kept in fresh water was studied. In addition to glutaraldehydeosmium tetroxide and simple osmium tetroxide fixation, a special method for the demonstration of chloride ions was used (Komnick, 1962, 1963). Based on the principle of silver chloride precipitation in the presence of chloride ions, the procedure showed positive results in the chloride cells of eels adapted to sea water. Smooth-surfaced tubules of the endoplasmic reticulum contained a material of medium to strong electron density, that was often in communication with the plasma membrane. The same material, always of very high density, was present in the intercellular spaces, thus forming conspicuous lines around cells. The silver precipitate was found very often in large quantities in the pits of chloride cells, having thereby the aspect of a secretory product. However, a direct communication between the system of endoplasmic reticulum tubules containing the silver reaction product with the above-mentioned masses of silver chloride was not demonstrated. Schultz (1958) first published an electron micrograph of these cells. Two features, numerous mitochondria and highly developed agranular endoplasmic reticulum, affirmed by all later investigators, have remained the most important criteria for the identification of chloride cells (Kessel and Beams, 1962; Philpott, 1962; Philpott and Copeland, 1963; Rhodin, 1964; Henrikson and Matoltsy, 1968). Kessel and Beams (1962) and Philpott and Copeland (1963) demonstrated pits, or apical cavities (Oberg, 1967) filled with an amorphous granular substance of medium electron density. (Threadgold and Houston, 1964). These cavities are found in animals adapted to sea water only, and correspond to the excretory vesicles described earlier by Copeland (1948). Philpott and Copeland demonstrated numerous vesicles and tubules in the cytoplasm surrounding the apical cavities and opening into them, possibly contributing to their granular material. Several authors attempted to demonstrate a chloride excretory function of chloride cells with the aid of some histochemical reactions. Copeland (1948), Datta Munshi (1964) and Philpott (1966) used silver techniques     

The dissociation of avidin–biotin complexes by guanidinium chloride

Avidin molecules in which a fraction of the four binding sites were occupied by biotin did not dissociate completely in 6.4m-guanidinium chloride. Only unoccupied subunits dissociated. The remainder recombined to form the tetrameric avidin-biotin complex. The rate at which unoccupied subunits were unfolded and dissociated was only decreased by one-half in species in which three of the four binding sites were occupied by biotin. These results can be explained by assuming that unfolding of unoccupied subunits followed by dissociation from the tetramer is initiated by penetration of guanidinium ions into the binding site and disorganization of this region of the subunit. When a site is occupied by biotin this pathway is blocked and the subunit does not unfold. Each subunit behaves independently and is not markedly stabilized when neighbouring subunits are occupied.     

The biochemical effects of potassium chloride on the silkworm, （ Bombyx mori L.）

The supplementation with 50, 100 and 150μg/mL potassium chloride to the fifth instar larvae of the silkworm Bombyx mori on fat body glycogen, protein, total lipids and haemolymph protein and trehalose were analyzed. The fat body glycogen and protein and haemolymph protein were increased significantly in all the treated groups; whereas fat body total lipids increased only in 100 and 150μg/mL and haemolymph trehalose increased only in 150μg/mL potassium chloride-treated groups when compared with those of the corresponding parameters of the carrier controls.     

Some biochemical aspects of the protective effect of strontium chloride on γ-irradiated rats

The effect of treatment with SrCl₂ (10 mg 100 g^–) on rats 15 min prior to whole body -irradiation (7.5 Gy) was studied. The hazardous effects of irradiation were greatly corrected in the treated group. The hyperglycemic effect and liver glycogen accumulation in the untreated group decreased to normal level. The enzymatic activities of serum alkaline phosphatase, alanine and aspartate aminotransferases, and lactate dehydrogenase were greatly affected, showing insignificant changes in the treated group of animals. Life span calculated on 50% survival was also significantly elongated by 36.3%. These results show the potentiality of SrCl₂ as a radioprotective agent. A proposed mechanism is discussed.     

Effect of potassium chloride and cationic drug on swelling,erosion and release from κ-carrageenan matrices

The basic objective of this work was to study the effect of model cationic drug metformin HCl on swelling and erosion and, in turn, the release of KCl and drug itself, from the κ-carrageenan matrices. Water uptake by the matrix up to 2 hours was found to increase with KCl concentration from the plain matrix. Erosion was not affected by concentration of KCl. Incorporation of drug favors water uptake, but in presence of KCl it was found to be reduced. Drugcontaining matrices have shown higher release of KCl as compared with plain batches. Drug release was retarded as KCl concentration increased up to 5%, above which the reduced cohesivity of the matrix caused increase in drug release.     

Transport of sodium and chloride across earthworm skin in vitro

We present a new invertebrate model for the study of epithelial sodium transport in tight epithelia, the earthworm integument. Dissected segments of earthworm integument were mounted in modified Ussing chambers and perfused with either pond water (PW) or earthworm ringer solution (ERS) on the apical side. In order to investigate ion transport under near-in vivo physiological conditions, measurements were performed under current-clamp conditions by monitoring the transepithelial potential (V _T), as well as the transepithelial resistance (R _T). These were recorded continuously and the virtual short circuit current (I _SC) was calculated. The integument has a high transepithelial resistance (R _T=9,037±502 Ω cm² for PW, n=24, and 11,055±1,320 Ω cm² for ERS, n=32). V _T was −3.7±2.2 mV for PW (n=24) and −1.5±1.0 mV for ERS (n=32), and I _SC was −0.57±0.30 μA/cm² for PW (n=24) and −0.44±0.24 μA/cm² for ERS (n=32). Only under PW, but not under ERS conditions, was there a pronounced inhibition of I _SC by low doses of amiloride or its analogues phenamil and benzamil. The resistance of the paracellular pathway was found to be very high. The terrestrial oligochaete Lumbricus seems especially adapted to the environmental conditions because it has an ultra-tight integument and a very fast up- and down-regulation of apical Na⁺ channels.     

Synthesis of an intensely sweet chlorodeoxysucrose: Mechanism of 4′-chlorination of sucrose by sulphuryl chloride

Reaction of 6-O-acetylsucrose¹ with sulphuryl chloride in chloroform-pyridine affords, after dechlorosulphation and acetylation, a mixture of two isomeric 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-d-galactopyranosyl 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-β-d-hexulofuranosides (6 and 7) and 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-d-galactopyranosyl 3,4-di-O-acetyl-1,6-dichloro-1,6-dideoxy-β-d-fructofuranoside (4). Chlorination of C-4, C-1′, and C-6′ occurs by direct displacement of the initially formed chlorosulphonyloxy groups by chloride ions, but displacement of the 4′-chlorosulphate is sterically hindered. The introduction of a 4′-chloro substituent involves ring opening of intermediate 3′,4′-epoxides by chloride ions, the ribo-epoxide producing the sorbo-isomer 6 and the lyxo-epoxide giving the fructo-isomer 7. The proposed mechanism is supported by the formation of 4-chloro-4-deoxyfructofuranosides when 3′,4′-lyxo-hexulofuranosides are treated with sulphuryl chloride under the same conditions.     

Regulation of swelling—activated chloride channels in embryonic chick heart cells

Swelling-activated Cl^- currents,I(Cl,swell),were measured during hyposmotic shock in white Leghorn embryonic chick heart cells using the whole-cell recording of patch-clamp technique.Genistein,an inhibitor of protein tyrosine kinase(PTK),suppressed I(Cl,swell).Under isosmotic condition phorbol 12-myristate 13-actetate(PMA),and activator of PKC,elicited the Cl^- current similar to that in hyposmotic solution,whereas hyposmotic shock did not elicit I(Cl,swell) in chelerythrine chloride(an inhibitor of PKC)-treated cells,Confocal microscopy experiments using FITC-phalloidin as a fluorescent label of F-actin showed that the actin network was moved from cortical region of the cell to the center after hyposmotic shock as compared with the image under isosmotic condition,When the cells were treated with cytochalasin B(CB)or cytochalasin D(CD)under isosmotic condition the disruption of the F-actin integrity was observed,and I(C,l,swell). The results suggested that the role of PTK,probably receptor tyrosine kinase,for regulation of I(Cl,swell) appeared to be at upstream site related to the role of F-actin.Then PKC signal pathway was activated somehow and finally change in the polymerization state of cytoskeleton led to activate the swelling-activated Cl^- channels.These results demonstrate clearly that PTK,PKC and F-actin are important factors for regulation of I(Cl,swell),in embryonic chick heart cells as compared with often controversial results reported in different cell types.     

Free radical-mediated addition of peracetylated 1-bromo-β-d-glucopyranosyl chloride to acrylonitrile

Dropwise addition of a benzene solution of tri-n-butylstannane to a solution of 2,3,4,6-tetra-O-acetyl-1-bromo-β-d-glucopyranosyl chloride in boiling benzene containing acrylonitrile in excess led predominantly, under photolytic conditions, to a mixture of nonononitriles, either chlorinated or unsaturated.     

Intracellular chloride activities in rabbit gallbladder: Direct evidence for the role of the sodium-gradient in energizing “Uphill” chloride transport

Summary Intracellular chloride activities, (Cl)_c, in rabbit gallbladder were determined by using conventional (KCl-filled) microelectrodes and Cl-selective, liquid ionexchanger, microelectrodes. The results indicate that in the presence of a normal Ringer's solution, (Cl)_c averages 35 mM; this value is 2.3 times that predicted for an equilibrium distribution across the mucosal and baso-lateral membranes. On the other hand, when the tissue is bathed by Na-free solutions, (Cl)_c declines to a value that does not differ significantly from that predicted for an equilibrium distribution.These results, together with those of Frizzellet al. (J. Gen. Physiol. 65:769, 1975) provide, for the first time, compelling evidence that (i) the movement of Cl from the mucosal solution into the cell is directed against an electrochemical potential difference (23 mV); and (ii) this movement is energized by coupling to the entry of Na down a steep electrochemical potential difference.Finally, our data suggest that (i) Cl exit from the cell across the basolateral membrane may be coupled to the co-transport of a cation or the countertransport of an anion; and (ii) the mechanism responsible for active Na extrusion from the cell across the baso-lateral membrane is rheogenic (electrogenic), and is not the result of a neutral Na-K exchange.     

Molecular structure,spectroscopic (FT-IR,FT-Raman,UV–vis), NBO,thermochemistry analysis of bis(thiourea)zinc(II) chloride crystals

The experimental and theoretical studies on the molecular structure and vibrational spectra of bis(thiourea)zinc(II) chloride (BTZC) crystals were investigated. The Fourier transform infrared, Fourier transform Raman and UV–vis spectra of BTZC were recorded. The molecular geometry and vibrational frequencies of BTZC in the ground state were calculated by using B3LYP with LANL2DZ as basis set. Comparison of the observed structural parameters of BTZC with single-crystal X-ray studies yields a good agreement. Vibrational analysis of the simultaneous IR and Raman activation of the Zn–Cl stretching mode in the molecule provides the evidence for the charge transfer interaction taking place within the molecule. The energy and oscillator strength are calculated by time-dependent density functional theory. The simulated spectra satisfactorily coincide with the experimental spectra.     

Synthesis of 4-thiophen-2′-yl-1,4-dihydropyridines as potentiators of the CFTR chloride channel

The gating of the CFTR chloride channel is altered by a group of mutations that cause cystic fibrosis. This gating defect may be corrected by small molecules called potentiators. Some 1,4-dihydropyridine (DHP) derivatives, bearing a thiophen-2-yl and a furanyl ring at the 4-position of the nucleus, were prepared and tested as CFTR potentiators. In particular, we evaluated the ability of novel DHPs to enhance the activity of the rescued ΔF508-CFTR as measured with a functional assay based on the halide-sensitive yellow fluorescent protein. Most DHPs showed an effect comparable to or better than that of the reference compound genistein. The potency was instead significantly improved, with some compounds, such as 3g, 3h, 3n, 4a, 4b, and 4d, having a half effective concentration in the submicromolar range. CoMFA analysis gave helpful suggestions to improve the activity of DHPs.     

Some observations on the minor products of the reaction of 2,2′-dilithiobiphenyl with mercuric chloride

Reaction of 2,2′-dilithiobiphenyl (formed from 2,2′-diiodobiphenyl and lithium in diethyl ether) with mercuric chloride gives the ortho-biphenylenemercury trimer (I) with 2,2′-bis(iodomercury)biphenyl (II) as an isolatable intermediate. The mass spectrum of impure 2,2′-bis(iodomercury)biphenyl at high sensitivity shows ion clusters which are interpreted as the ions of a polyphenyl iodomercury complex [Hg₃(C₆H₄)₄I₂] (III) which is identified as a further intermediate in the production of ortho-biphenylenemercury trimer and several iodomercury cations of general formula [Hg_xI_y]⁺, where x, y = 1, 2, 3. A fragmentation scheme is presented to account for these unusual iodomercury cations. Reaction mechanisms are presented to account for the production of II and III.     

Interaction of ruthenium(III) chloride with bis(3,5-dimethylpyrazol-1-yl)methane oxyanions, potential κ-N,N,O scorpionates

When RuCl₃ was set to react with both bis(3,5-dimethylpyrazol-1-yl)acetate (bdmpza) and bis(3,5-dimethylpyrazol-1-yl)methane sulfonate (bdmpzsa) new ruthenium(II) complexes were obtained. The reduction of ruthenium(III) was studied by the NMR Evans method and spectrophotometrically, for 1:1 (Ru:L) molar ratios. Using the Evans method pseudo first-order constants of 2.5 × 10⁻³ s⁻¹ (bdmpzsa) and 3.9 × 10⁻³ s⁻¹ (bdmpza) were obtained in DMSO-d₆ (2% t-butanol) solutions. Spectrophotometrically the corresponding constants were also calculated: 1.1 × 10⁻³ s⁻¹ for bdmpzsa, and 1.6 × 10⁻³ s⁻¹, for bdmpza. Both ligands behave as κ³-N,N,O scorpionates but with a weak oxyanionic coordination to the metal, susceptible to be substituted with NEt₃ for a 1:1 molar ratio.     

The chemistry of polyhalozirconates. Part 1. Zirconium oxide chloride,a source of the anions ZrCl5− and ZrCl62−

Conductimetric studies of thionyl chloride solutions of ZrCl₄ and ZrOCl₂·8H₂O indicate that the solvated species in the two solutions are different. From such solutions the synthesis of two types of pentachlorozirconates are reported. The synthesis of hexachlorozirconates from each solution is also reported.