Replacement Of Cl Research Articles

Constructing a Catalytic Cycle for C-F to C-X (X = O, S, N) Bond Transformation Based on Gold-Mediated Ligand Nucleophilic Attack.

A tricoordinated gold(I) chloride complex, tBuXantphosAuCl, supported by a sterically bulky 9,9-dimethyl-4,5-bis(di-tert-butylphosphino)xanthene ligand (tBuXantphos) was synthesized. This complex features a remarkably longer Au-Cl bond length [2.632(1) Å] than bicoordinated linear gold complexes (2.27-2.30 Å) and tricoordinated XantphosAuCl [2.462(1) Å]. Single-crystal X-ray diffraction analysis of a cocrystal of tBuXantphosAuCl and pentafluoronitrobenzene (PFNB) and UV-vis spectroscopic titration experiments revealed the existence of an anion-π interaction between the Cl anion ligand and PFNB. Stoichiometric reaction between PFNB and tBuXantphosAuOtBu, after replacement of Cl by a more nucleophilic tBuO anion ligand, showed higher reactivity and para selectivity in the transformation of C-F to C-OtBu bond, distinctively different from that when only KOtBu was used (ortho selectivity) under the identical condition. Mechanistic studies including density functional theory calculations suggested a gold-mediated nucleophilic ligand attack of the C-F bond pathway via an SNAr process. On the basis of these results, using trimethylsilyl derivatives TMS-X (X = OMe, SEt, NEt2) as the nucleophilic ligand source and the fluorine acceptor, catalytic transformation of the C-F bond of aromatic substrates to the C-X (X = O, S, N) bond was achieved with tBuXantphosAuCl as the catalyst (up to 20 turnover numbers).

Effect of chemical and physical doping with iodine on the optical and dielectric properties of poly(vinyl chloride)

Iodination of poly(vinyl chloride) (PVC) was prepared by addition of I2 or I− through physical adsorption and chemical modification techniques forming (PVC–I2) (composite I) and (PVC–I−) (composite II), respectively.Investigations were performed using TGA, DSC, FTIR, UV–vis absorbance analyses and ac conductivity measurements. The activation energy of decomposition, ΔEd, was found to be 215.15kJ/mole and 43.1kJ/mole for PVC and composite II, respectively. Both direct and indirect optical transitions near the absorption edge are observed. Addition of I2 or I− decreases the optical energy gap for PVC. The chemical replacement of Cl− ion in PVC matrix with I− ion in composite II increases the electrical conductivity by two orders. A possible conduction mechanisms are suggested.

On the Colossal and Highly Anisotropic Thermal Expansion Exhibited by Imidazolium Salts

The imidazolium salts 1-ethyl-2,3-dimethylimidazolium chloride, Edimim[Cl], and bromide, Edimim[Br], exhibit negative and positive thermal expansions, as determined by variable-temperature synchrotron powder X-ray diffraction experiments. Both compounds crystallize in the same monoclinic centrosymmetric space group, showing an anisotropic H-bonding network and imidazolium–imidazolium π+–π+ interactions, which have been corroborated by density functional theory studies. The chloride derivative displays a highly anisotropic thermal expansion with a colossal positive coefficient along one direction. Replacement of Cl– by Br– in the same crystal structure produces an increase of the colossal coefficient and induces a biaxial negative thermal expansion. By studying the molecular vibration factors and the H-bonding framework in their crystals as a function of temperature, it was possible to rationalize at the molecular level the mechanism for the observed anomalies in thermal expansion.

Phosphorus–nitrogen compounds: Part 31. Syntheses, structural and stereogenic properties, in vitro cytotoxic and antimicrobial activities, and DNA interactions of bicyclotetraphosphazenes containing bulky side group

Hexachlorocyclotriphosphazene, N3P3Cl6, and octachlorocyclotetraphosphazene, N4P4Cl8, were reacted with K2N2O2 salt of symmetric tetradentate ligand to obtain spiro-bino-spiro [(sbs) (2)] and 2,6-spiro-ansa-spiro [(2,6-sas) (3)] phosphazenes, respectively. The sbs was obtained in a very poor yield, whereas, 2,6-sas was obtained in a moderate yield. The derivatives of 2,6-sas with mono- and diamines were synthesized. When the reactions were carried out, one equimolar amount of 2,6-sas with an excess pyrrolidine, piperidine, morpholine, 1,4-dioxa-8-azaspiro[4,5]decane (DASD), N-methylethane-1,2-diamine, N-ethylethane-1,2-diamine and N-methylpropane-1,3-diamine, along with the fully substituted 2,6-sas-cyclotetraphosphazene derivatives (4a, 4b and 5a–7a), were prepared. However, the excess morpholine and DASD with 2,6-sas yielded the geminal bis- (4c and 4e) and tris- (4d and 4f) cyclotetraphosphazenes, respectively. The Cl replacement reaction of 2,6-sas with one equimolar amount of 7 led to the formation of partly substituted 2,6-sas (7b). The structures of the compounds were verified by elemental analyses, MS, FTIR, 1H, 13C{1H}, 31P NMR, HSQC, HMBC and X-ray crystallography (for 3 and 4a) techniques. All the 2,6-sas cyclotetraphosphazenes (except 3, 4a and 4b) have stereogenic P-atoms. All the compounds were screened for antibacterial and antifungal activities against bacteria and yeast strains. The interactions of the compounds with supercoiled plasmid pBR322 DNA were investigated. The evaluations for cytotoxic activity, and apoptotic and necrotic effects against A549 lung cancer and L929 fibroblast cell lines were introduced.

The performance of silver modified tungsten oxide for the removal of 2-CP and 2-NP in sunlight exposure: Optical, electrochemical and photocatalytic properties

The optical and electrochemical characterization of the synthesized Ag+ modified WO3 photocatalysts was performed and its photocatalytic activity was estimated in the visible region (420–800nm) of sunlight for the degradation of 2-chloro and 2-nitrophenol. The catalysts with the varying loading of Ag+ ranging from 0.5% to 10%, exhibited significantly higher activity as compared to pure WO3. Attempts were made to correlate the enhanced activity of Ag+ loaded catalysts with the optical and electrochemical properties. At lower loading (up to 1% Ag+), the enhanced degradation was attributed to the excited electron trap and transfer ability of surface mounted Ag+ species, while the synergic effect between the WO3 support and surface Ag2O resulted the same at higher loadings. The electrochemical properties of the synthesized powders, in comparison with pure WO3, also supported the same findings. The identification of the intermediates and the estimation of the released anions evidenced the contribution of both hydroxyl radicals (HO) and superoxide anion (O2−) radicals in the degradation process. The identification of aliphatic oxygenates as majority intermediates and release of respective ions verified the replacement of Cl− and NO2 groups, insertion of oxygen and aromatic ring cleavage.

The impacts of firework burning at the Chinese Spring Festival on air quality: insights of tracers, source evolution and aging processes

Abstract. To understand the impact of firework-burning (FW) particles on air quality and human health during the winter haze period, 39 elements, 10 water-soluble ions and 8 fractions of carbonaceous species in atmospheric PM2.5 in Nanjing were investigated during the 2014 Chinese Spring Festival (SF). Serious regional haze pollution persisted throughout the entire sampling period, with PM2.5 averaging at 113 ± 69 μg m−3 and visibility at 4.8 ± 3.2 km. The holiday effect led to almost all the chemical species decreasing during the SF, except for Al, K, Ba and Sr which were related to FW. The source contributions of coal combustion, vehicle emission and road dust decreased dramatically, whereas FW contributed to about half of the PM2.5 during the SF period. The intensive emission of FW particles on New Year's Eve accounted for 60.1% of the PM2.5. Fireworks also obviously modified the chemical compositions of PM2.5, with 39.3% contributed by increased organic matter, followed by steadily increased loadings of secondary inorganic ions. The aging processes of the FW particles lasted for about 4 days reflected by the variations of Ba, Sr, NH4+, NO3−, SO42− and K+, characterized by heterogeneous reactions of SO2 and NOx on crustal materials directly from FW, the replacement of Cl− by NO3− and SO42−, coating of NO3− and SO42− on soot, formation of secondary organic aerosols and metal-catalyzed formation of NO3− and SO42− at higher relative humidity. During aging, the main contributors to the extinction coefficient shifted from elemental carbon and organic matter to ammonium sulfate. The particles raised higher cancer risk of 1.62 × 10−6 by heavy metals (especially for Cd and As). This study provided detailed composition data and first comprehensive analysis of the aging processes of FW particles during the serious haze pollution period and their potential impact on human health.

Synthesis and Antimicrobial and Antifungal Activities of 3-Substituted 1-Cyanomethyl-3,4-Dihydroisoquinolinium Chlorides

3-Substituted [3,4-dihydroisoquinolin-1(2H)-ylidene]acetonitriles were synthesized via replacement of Cl by a cyano group in the corresponding 1-chloromethylisoquinolines. The hydrochlorides of the synthesized compounds exhibited weak antimicrobial and antifungal activities. The maximum activity against Staphylococcus aureus, Escherichia coli, and Candida albicans was observed for the compound with a 3-spiro-cyclopentyl radical, the MIC of which was 250 g/mL.

Activation of ATP Secretion via Volume-Regulated Anion Channels by Sphingosine-1-Phosphate in Raw Macrophages

We report the activation of outwardly rectifying anion currents by sphingosine-1-phosphate (S1P) in the murine macrophage cell line RAW 264.7. The S1P-induced current is mainly carried by anions, because the reversal potential of the current was shifted by replacement of extracellular Cl− by glutamate− but not when extracellular Na+ was substituted by Tris+. The inhibition of the current by hypertonic extracellular or hypotonic intracellular solution as well as the inhibitory effects of NPPB, tamoxifen, and glibenclamide indicates that the anion current is mediated by volume-regulated anion channels (VRAC). The S1P effect was blocked by intracellular GDPβS and W123, which points to signaling via the S1P receptor 1 (S1PR1) and G proteins. As cytochalasin D diminished the action of S1P, we conclude that the actin cytoskeleton is involved in the stimulation of VRAC. S1P and hypotonic extracellular solution induced secretion of ATP from the macrophages, which in both cases was blocked in a similar way by typical VRAC blockers. We suppose that the S1P-induced ATP secretion in macrophages via activation of VRAC constitutes a functional link between sphingolipid and purinergic signaling in essential processes such as inflammation and migration of leukocytes as well as phagocytosis and the killing of intracellular bacteria.

Regulation of ClC-3 Cl-/H+ Transport and “Gating” Transients by Chloride Pathway Residues and External Protons

We investigated ClC-3 ion transport properties by employing a “ClC-5/3” plasmid, consisting of the ClC-5 N-terminal (M1-A46) linked to the core ClC-3 protein. This ClC-3 protein is redirected to the plasma membrane of HEK cells. Functionally it exhibits rapidly activated, outwardly rectifying sustained ion currents (ISS) representing coupled Cl-/H+ transport, and prominent “on/off” transient gating charge (Q) movements, as recently described for a ClC-3 mutant (Guzman et al, 2013, ACS Chem Neurosci). Interpreting Q to represent movements of unprotonated (ie, incompletely cycling) “Gluext”/ E224, ClC-3 exhibits low transport efficiency compared to ClC-5 or ClC-4, which exhibit larger ISS and much smaller Q. Replacement of external Cl- with SCN- increases ClC-3 currents by 3-4 fold, and reduces H+ coupling by ∼90%. Removal of a conserved tyrosine (Y630S, V) positioned at the intersection of the Cl-/H+ pathways (Accardi et al, 2006, JMB) greatly increases currents and decreases Q. For Y630S, H+ coupling is reduced by ∼50%; SCN substitution decreases rather than increases current, and eliminates H+ transport. An M568A mutant moderately impacts transport, increasing currents and decreasing Q by <50%. Reduction of external pH (pH 6 or 5) weakly inhibits ClC-3 ISS, but markedly reduces Q, and shifts the Q(V) relationship toward more positive voltages. These results are consistent with external protons inhibiting cycling by neutralization of Gluext. An endogenous Cl- current activated at pH5 (Iacid) has slow activation kinetics and lacks gating transients, is inhibited by 60-120 microM phloretin, and is decreased by ClC-3 expression. Thus, Iacid is readily distinguished from expressed ClC-3 transport. These data indicate that ClC-3 H+ coupling and transport is influenced by anion interaction, and by external protons, as suggested for the bacterial ClCec-1.

Synthesis, characterisation and antibacterial activity of [(p-cym)RuX(L)](+/2+) (X = Cl, H2O; L = bpmo, bpms) complexes.

Mononuclear half-sandwiched complexes [(p-cym)RuCl(bpmo)](ClO4) {[1](ClO4)} and [(p-cym)RuCl(bpms)](PF6) {[2](PF6)} have been prepared by reacting heteroscorpionate ligands bpmo = 2-methoxyphenyl-bis(3,5-dimethylpyrazol-1-yl)methane and bpms = 2-methylthiophenyl-bis(3,5-dimethylpyrazol-1-yl)methane, respectively, with a dimeric precursor complex [(p-cym)RuCl(μ-Cl)]2 (p-cym = 1-isopropyl-4-methylbenzene) in methanol. The corresponding aqua derivatives [(p-cym)Ru(H2O)(bpmo)](ClO4)2 {[3](ClO4)2} and [(p-cym)Ru(H2O)(bpms)](PF6)2 {[4](PF6)2} are obtained from {[1](ClO4)} and {[2](PF6)}, respectively, via Cl(-)/H2O exchange process in the presence of appropriate equivalents of AgClO4/AgNO3 + KPF6 in a methanol-water mixture. The molecular structures of the complexes {[1]Cl, [3](ClO4)2 and [4](PF6)(NO3)} are authenticated by their single crystal X-ray structures. The complexes show the expected piano-stool geometry with p-cym in the η(6) binding mode. The aqua complexes [3](ClO4)2 and [4](PF6)2 show significantly good antibacterial activity towards E. coli (gram negative) and B. subtilis (gram positive) strains, while chloro derivatives ({[1](ClO4)} and {[2](PF6)} are found to be virtually inactive. The order of antibacterial activity of the complexes according to their MIC values is [1](ClO4) (both 1000 μg mL(-1)) < [2](PF6) (580 μg mL(-1) and 750 μg mL(-1)) < [3](ClO4)2 (both 100 μg mL(-1)) < [4](PF6)2 (30 μg mL(-1) and 60 μg mL(-1)) for E. coli and B. subtilis strains, respectively. Further, the aqua complexes [3](ClO4)2 and [4](PF6)2 show clear zones of inhibition against kanamycin, ampicillin and chloramphenicol resistant E. coli strains. The detailed mechanistic aspects of the aforesaid active aqua complexes [3](ClO4)2 and [4](PF6)2 have been explored, and it reveals that both the complexes inhibit the number of nucleoids per cell in vivo and bind to DNA in vitro. The results indeed demonstrate that both [3](ClO4)2 and [4](PF6)2 facilitate the inhibition of bacterial growth by binding to DNA.

Phosphorus-nitrogen compounds: part 30. Syntheses and structural investigations, antimicrobial and cytotoxic activities and DNA interactions of vanillinato-substituted NN or NO spirocyclic monoferrocenyl cyclotriphosphazenes.

The gradual Cl replacement reactions of NN (1-3) or NO spirocyclic monoferrocenyl cyclotriphosphazenes (4 and 5) with the potassium salt of 4-hydroxy-3-methoxybenzaldehyde (potassium vanillinate) resulted in the mono (1a-5a), geminal (gem-1b-5b), non-geminal (cis-5b and trans -1b-4b), tri (1c, 3c-5c) and tetra-vanillinato-substituted phosphazenes (1d-5d). All the phosphazene derivatives have stereogenic P-center(s), except tetra-substituted ones. The vanillinatophosphazenes have reversible voltammograms with one-electron anodic and cathodic peaks which are attributed to ferrocenyl redox probe. The structures of the new phosphazene compounds were determined by FTIR, MS, (1)H, (13)C{(1)H} and (31)P{(1)H} NMR spectral data. The solid-state structure of cis -5b was examined by single-crystal X-ray diffraction techniques. In addition, the compounds were tested in HeLa cancer cell lines using MTT assay. The 12 phosphazene derivatives were screened for antimicrobial activity, and 3c was very effective against S. aureus even at 4.88µM concentration, taking into account the MIC values. Besides, interactions between the phosphazenes and pBR322 plasmid DNA were also investigated.

HCl Oxidation for Sustainable Cl2 Recycle over the CexZr1–xO2 Catalysts: Effects of Ce/Zr Ratio on Activity and Stability

CexZr1–xO2 oxides prepared by a soft reactive grinding (SRG) procedure have been investigated as the catalysts for HCl oxidation. The results show that the catalytic activities and stabilities of CexZr1–xO2 oxides are remarkably dependent on the Ce/Zr ratio. A correlation between the physicochemical properties and catalytic performances of these samples reveals that the cubic phase in CexZr1–xO2 with higher oxygen storage capacity (OSC) is more active for HCl oxidation, but the tetragonal phase is crucial to the stability of the catalysts. The Ce0.5Zr0.5O2 catalyst with mixed phases and the highest OSC (80 μmolO2·gcat–1) exhibits an excellent activity (1.89 gCl2·gcat–1·h–1 at 430 °C) and stability (300 h) in the target reaction. Kinetic studies show that both O2 and HCl competed for the active sites rendering desorption of surface Cl as the rate-determining step. Accelerating the replacement of surface Cl by O2 is essential for improving the activity of Ce0.5Zr0.5O2.

Activation of ATP secretion via volume-regulated anion channels by sphingosine-1-phosphate in RAW macrophages.

We report the activation of outwardly rectifying anion currents by sphingosine-1-phosphate (S1P) in the murine macrophage cell line RAW 264.7. The S1P-induced current is mainly carried by anions, because the reversal potential of the current was shifted by replacement of extracellular Cl(-) by glutamate(-) but not when extracellular Na(+) was substituted by Tris(+). The inhibition of the current by hypertonic extracellular or hypotonic intracellular solution as well as the inhibitory effects of NPPB, tamoxifen, and glibenclamide indicates that the anion current is mediated by volume-regulated anion channels (VRAC). The S1P effect was blocked by intracellular GDPβS and W123, which points to signaling via the S1P receptor 1 (S1PR1) and G proteins. As cytochalasin D diminished the action of S1P, we conclude that the actin cytoskeleton is involved in the stimulation of VRAC. S1P and hypotonic extracellular solution induced secretion of ATP from the macrophages, which in both cases was blocked in a similar way by typical VRAC blockers. We suppose that the S1P-induced ATP secretion in macrophages via activation of VRAC constitutes a functional link between sphingolipid and purinergic signaling in essential processes such as inflammation and migration of leukocytes as well as phagocytosis and the killing of intracellular bacteria.

Adsorption Properties of Two-Dimensional NaCl: A Density Functional Theory Study of the Interaction of Co, Ag, and Au Atoms with NaCl/Au(111) Ultrathin Films

Recent experiments have shown that Co atoms deposited on NaCl/Au(111) ultrathin films give rise to spontaneous substitutional doping of the NaCl layer (Li et al. Phys. Rev. Lett. 2014, 112, 026102 ). In this work, the interaction of Co atoms deposited on NaCl/Au(111) films is investigated by means of density functional theory calculations. Co atoms have been adsorbed on various sites of the surface of unsupported and supported two- and three-layer NaCl films; incorporation of the Co atoms in interstitial positions or replacement of Na and Cl lattice ions has also been investigated. The Co adsorption properties are compared with those of Ag and Au atoms. We found that all metal atoms interact strongly with NaCl/Au(111) films, giving rise to large structural distortions of the insulating layer. Co, Ag, or Au incorporation in interstitial positions between the first and second NaCl layers is thermodynamically preferred over adsorption on surface sites. The results show the reactivity of NaCl with Co is highe...

Location and function of the high-affinity chloride in the oxygen-evolving complex – Implications from comparing studies on Cl−/Br−/I−-substituted photosystem II prepared using two different methods

The high-affinity chloride ion (Cl−) is known to play a key role in water oxidation in photosystem II (PSII). Recent crystallographic studies revealed two Cl− binding sites in PSII. To examine whether these two Cl− ions are correlated to the high-affinity Cl−, we prepared Cl−/Br−/I−-substituted PSII samples from both higher plants and cyanobacteria by using two different protocols: one was the method used in the crystallographic study (Type 1) and the other was a method developed recently to ensure the efficient replacement of Cl− (Type 2). While only minor effects were observed in the Type 1 preparation, efficient Br−/I−substitution by the Type 2 protocol led to significant changes in the EPR properties of the oxygen-evolving complex (OEC) and the TyrZ, as well as in oxygen-evolving activities. These results are discussed in terms of the binding site of the high-affinity Cl− relative to the two Cl− ions revealed by the recent X-ray structural data.

Interactions between permeation and gating in the TMEM16B/anoctamin2 calcium-activated chloride channel.

At least two members of the TMEM16/anoctamin family, TMEM16A (also known as anoctamin1) and TMEM16B (also known as anoctamin2), encode Ca(2+)-activated Cl(-) channels (CaCCs), which are found in various cell types and mediate numerous physiological functions. Here, we used whole-cell and excised inside-out patch-clamp to investigate the relationship between anion permeation and gating, two processes typically viewed as independent, in TMEM16B expressed in HEK 293T cells. The permeability ratio sequence determined by substituting Cl(-) with other anions (PX/PCl) was SCN(-) > I(-) > NO3 (-) > Br(-) > Cl(-) > F(-) > gluconate. When external Cl(-) was substituted with other anions, TMEM16B activation and deactivation kinetics at 0.5 µM Ca(2+) were modified according to the sequence of permeability ratios, with anions more permeant than Cl(-) slowing both activation and deactivation and anions less permeant than Cl(-) accelerating them. Moreover, replacement of external Cl(-) with gluconate, or sucrose, shifted the voltage dependence of steady-state activation (G-V relation) to more positive potentials, whereas substitution of extracellular or intracellular Cl(-) with SCN(-) shifted G-V to more negative potentials. Dose-response relationships for Ca(2+) in the presence of different extracellular anions indicated that the apparent affinity for Ca(2+) at +100 mV increased with increasing permeability ratio. The apparent affinity for Ca(2+) in the presence of intracellular SCN(-) also increased compared with that in Cl(-). Our results provide the first evidence that TMEM16B gating is modulated by permeant anions and provide the basis for future studies aimed at identifying the molecular determinants of TMEM16B ion selectivity and gating.

New Synthesis and Reactions of Ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate

Synthesis of ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate 5 has been achieved via abnormal Beckmann rearrangement of o‐chloroaldehyde 1. Reaction of o‐aminocarbonitrile 5 with concentrated H2SO4 furnished expected o‐aminocarboxamide pyrazole 6. Key intermediates o‐aminocarbonitrile 5 and o‐aminocarboxamide 6 were successfully utilized for the synthesis of pyrazolopyrimidine derivatives. The replacement of Cl in o‐chlorocarbonitrile 3 with secondary amine furnished new synthon 13, which was further used for the synthesis of polysubstituted heterocycles. The obtained new products were well characterized by IR, 1H and 13C NMR, and mass spectra.

Halide Ion Effects on HumanEther-à-go-goRelated Gene Potassium Channel Properties

The human Ether-à-go-go related gene (hERG) potassium channel has been widely used to counter screen potential pharmaceuticals as a biomarker to predict clinical QT prolongation. Thus, higher throughput assays of hERG are valuable for early in vitro screening of drug candidates to minimize failure in later-stage drug development due to this potentially adverse cardiac risk. We have developed a novel method utilizing potassium fluoride to improve throughput of hERG counter screening with an automated patch clamp system, PatchXpress 7000A. In that method, ∼50% substitution of internal Cl− with F− greatly increases success rate without substantially altering the biophysical properties of the hERG channel or compromising data quality. However, effect of F− or other halide ions on hERG channel properties has not been studied in detail. In this study, we examined effects of complete replacement of Cl− in internal solution with halide ions, F−, or Br−. We found that (1) F− slightly shifts the voltage dependence of hERG channel activation to more positive voltages, while Br− shifts it to more negative voltages; (2) Br− shifts to more positive voltages both the inactivation–voltage relationship and the peak position of channel full activation of hERG; (3) F− slows hERG activation, while both F− and Br− make the channel close faster; (4) neither F− nor Br− have any effect on hERG inactivation kinetics. In conclusion, compared to Cl−, F− has subtle effect on hERG activation, while Br− has distinct effects on certain, but not all biophysical properties of hERG channel.

Phosphorus–nitrogen compounds: Part 28. Syntheses, structural characterizations, antimicrobial and cytotoxic activities, and DNA interactions of new phosphazenes bearing vanillinato and pendant ferrocenyl groups

The gradually Cl replacement reactions of spirocyclic mono (1 and 2) and bisferrocenyl cyclotriphosphazenes (3–5) with the potassium salt of 4-hydroxy-3-methoxybenzaldehyde (potassium vanillinate) gave mono (1a–5a), geminal (gem-1b–5b), non-geminal (cis-1b, cis-5b and trans-2b–5b), tri (1c–5c) and tetra-substituted phosphazenes (1d–5d). Some phosphazenes have stereogenic P-center(s). The chirality of 4c was verified using chiral HPLC column. Electrochemical behaviors were influenced only by the number of ferrocene groups, but not the length of the amine chains and the substituent(s). The structures of the new phosphazenes were determined by FTIR, MS, 1H, 13C and 31P NMR, HSQC and HMBC spectral data. The solid-state structures of cis-1b and 4d were examined by single crystal X-ray diffraction techniques. The twelve phosphazene derivatives were screened for antimicrobial activity and the compounds 5a, cis-1b and 2c exhibited the highest antibacterial activity against G(+) and G(−) bacteria. In addition, it was found that overall gem-1b inhibited the growth of Mycobacterium tuberculosis. The compounds 1d, 2d and 4d were tested in HeLa cancer cell lines. Among these compounds, 2d had cytotoxic effect on HeLa cell in the first 48h. Moreover, interactions between compounds 2a, gem-1b, gem-2b, cis-1b, 2c, 3c, 4c, 5c, 1d, 2d and 4d, and pBR322 plasmid DNA were investigated.

Role of Na+–H+ exchange in the modulation of L-type Ca2+ current during fluid pressure in rat ventricular myocytes

Application of fluid pressure (FP) using pressurized fluid flow suppresses the L-type Ca2+ current through both enhancement of Ca2+ release and intracellular acidosis in ventricular myocytes. As FP-induced intracellular acidosis is more severe during the inhibition of Na+–H+ exchange (NHE), we examined the possible role of NHE in the regulation of ICa during FP exposure using HOE642 (cariporide), a specific NHE inhibitor. A flow of pressurized (∼16dyn/cm2) fluid was applied onto single rat ventricular myocytes, and the ICa was monitored using a whole-cell patch-clamp under HEPES-buffered conditions. In cells pre-exposed to FP, additional treatment with HOE642 dose-dependently suppressed the ICa (IC50=0.97±0.12μM) without altering current–voltage relationships and inactivation time constants. In contrast, the ICa in control cells was not altered by HOE642. The HOE642 induced a left shift in the steady-state inactivation curve. The suppressive effect of HOE642 on the ICa under FP was not altered by intracellular high Ca2+ buffering. Replacement of external Cl− with aspartate to inhibit the Cl−-dependent acid loader eliminated the inhibitory effect of HOE642 on ICa. These results suggest that NHE may attenuate FP-induced ICa suppression by preventing intracellular H+ accumulation in rat ventricular myocytes and that NHE activity may not be involved in the Ca2+-dependent inhibition of the ICa during FP exposure.