Related Quaternary Ammonium Research Articles

Functional Characterization of a Novel SMR-Type Efflux Pump RanQ, Mediating Quaternary Ammonium Compound Resistance in Riemerella anatipestifer.

Riemerella anatipestifer (R. anatipestifer) is a multidrug-resistant bacterium and an important pathogen responsible for major economic losses in the duck industry. Our previous study revealed that the efflux pump is an important resistance mechanism of R. anatipestifer. Bioinformatics analysis indicated that the GE296_RS02355 gene (denoted here as RanQ), a putative small multidrug resistance (SMR)-type efflux pump, is highly conserved in R. anatipestifer strains and important for the multidrug resistance. In the present study, we characterized the GE296_RS02355 gene in R. anatipestifer strain LZ-01. First, the deletion strain RA-LZ01ΔGE296_RS02355 and complemented strain RA-LZ01cΔGE296_RS02355 were constructed. When compared with that of the wild-type (WT) strain RA-LZ01, the mutant strain ΔRanQ showed no significant influence on bacterial growth, virulence, invasion and adhesion, morphology biofilm formation ability, and glucose metabolism. In addition, the ΔRanQ mutant strain did not alter the drug resistance phenotype of the WT strain RA-LZ01 and displayed enhanced sensitivity toward structurally related quaternary ammonium compounds, such as benzalkonium chloride and methyl viologen, which show high efflux specificity and selectivity. This study may help elucidate the unprecedented biological functions of the SMR-type efflux pump in R. anatipestifer. Thus, if this determinant is horizontally transferred, it could cause the spread of quaternary ammonium compound resistance among bacterial species.

Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts.

A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes 3a–h and related quaternary ammonium salts 4a–h were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series 3 and 4 to be potent cytotoxins with submicromolar CC50 values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, 3a–h are cytotoxic towards a number of leukemic and colon cancer cells. 4b,c lowered the mitochondrial membrane potential in CEM cells, and 4d induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely 3c,d and 4c–e, were identified as lead molecules that have drug-like properties.

Epoxidation of allyl chloride with H2O2 catalyzed by three structurally related quaternary ammonium modified polyoxophosphotungstates

The one-step epoxidation of allyl chloride has always been a great challenge for the industrial production. The key of this technology is to find efficient and friendly catalyst. In this paper, three structurally related quaternary ammonium modified polyoxophosphotungstates were synthesized by green and facile method. Among them, [C16H33(CH3)3N]3PW4O24 and [π-C5H5NC16H33]3PW4O24 are reaction-controlled phase transfer catalyst (RPTC) and [(C18H37)2(CH3)2N]3PW4O24 is temperature-controlled phase transfer catalyst (TPTC). All three catalysts could achieve the epoxidation of allyl chloride with equimolar H2O2 under solvent-free and mild conditions. Moreover, the catalysts exhibited excellent catalytic performance and reusability. The catalytic mechanism was explored by FT-IR spectroscopy. The results of kinetic experiments show that the chain length of alkanes and heterocyclic structure of cations have a great influence on the catalytic activity of the catalysts.

Conjugation, Substituent, and Solvent Effects on the Photogeneration of Quinone Methides.

4- and 5-arylethynyl water-soluble Mannich bases and related quaternary ammonium salts were synthesized and investigated as a model of conjugated quinone methide precursors (QMPs) by UV-vis light activation. Preparative photohydration and trapping reactions by thiols were studied, together with the detection of both transient QMs and competing QMP lowest triplet excited states (T1), by laser flash photolysis. The efficiency of the arylethynyl derivatives as QMPs was remarkably affected by structural features (i.e., conjugating arylethynyl moieties, substituents, and leaving groups) and protic vs aprotic solvation. Our collective data clarify the dichotomy in the photoreactivity of conjugated Mannich bases and related quaternary ammonium salts as alkylating agents and singlet oxygen sensitizers.

A new cucurbit[6]uril-based ion-selective electrode for acetylcholine with high selectivity over choline and related quaternary ammonium ions

Detection of acetylcholine (ACh+) with high sensitivity and selectivity in the presence of interfering ions including choline (Ch+) poses a significant analytical challenge. A cucurbit[6]uril derivative, (allyloxy)12CB[6], forms a stable 1:1 inclusion complex with ACh+ but does not interact significantly with Ch+ in solution. Based on this result, we prepared ion-selective electrodes (ISEs) for ACh+ using (allyloxy)12CB[6] as an ionophore. The (allyloxy)12CB[6]-based ISEs detect ACh+ with unprecedentedly high selectivity over Ch+ as well as other interfering ions such as dopamine, NH4 +, and .

The Neuromuscular Blocking Action of Tetraethylammonium

Abstract The abnormally low activity of tetraethylammonium at the neuromuscular junction of the rat-diaphragm has been investigated. It seems possible to explain this lack of action in terms of the charge delocalisation and the stereochemistry of tetraethylammonium. The neuromuscular blocking activities of tetraethylammonium, isomers of it and related quaternary ammonium compounds have been determined and the structure activity relationships are discussed

The absorption of bretylium and related quaternary ammonium salts from the alimentary tract.

Abstract N-Methyl-14C-labelled bretylium was injected into the lumen of segments of the gastrointestinal tract of cats prepared so that blood draining from these segments could be collected for analysis. The drug was not absorbed from the stomach. The concentration of drug in the venous blood from the duodenum rose steadily during 1.5–2 hr. but then declined to a value slightly exceeding that in the systemic blood. The greater part of the dose was not absorbed. Bretylium slowly traversed rat duodenum (mucosa to serosa) in vitro and the rate was not affected by factors that can influence carbohydrate metabolism. Transfer proceeded equally well from serosa to mucosa. To investigate means of obtaining better absorption of quaternary ammonium anti-adrenergic drugs a close analogue of bretylium bearing a choline residue was phosphorylated to give a phosphoric ester betaine (III). This was about twice as active by the oral route in cats as the parent drug, in which form it was excreted in the urine.

Activation and block of mouse muscle-type nicotinic receptors by tetraethylammonium

We have studied the activation and inhibition of the mouse muscle adult-type nicotinic acetylcholine receptor by tetraethylammonium (TEA) and related quaternary ammonium derivatives. The data show that TEA is a weak agonist of the nicotinic receptor. No single-channel clusters were observed at concentrations as high as 5 mM TEA or in the presence of a mutation which selectively increases the efficacy of the receptor. When coapplied with 1 mM carbamylcholine (CCh), TEA decreased the effective opening rate demonstrating that it acts as a competitive antagonist of CCh-mediated activation. Kinetic analysis of currents elicited by CCh and TEA allowed an estimate of receptor affinity for TEA of about 1 mM, while an upper limit of 10 s−1 could be set for the wild-type channel-opening rate constant for receptors activated by TEA alone. At millimolar concentrations, TEA inhibited nicotinic receptor currents by depressing the single-channel amplitude. The effect had an IC50 of 2–3 mM, depending on the conditions of the experiment, and resembled a standard open-channel block. However, the decrease in channel amplitudes was not accompanied by an increase in the mean burst duration, indicating that a linear open-channel blocking mechanism is not applicable. Upon studying block by other nicotinic receptor ligands it was found that block by CCh, tetramethylammonium and phenyltrimethylammonium can be accounted for by the sequential blocking mechanism while block in the presence of methyltriethylammonium, ethyltrimethylammonium or choline was inconsistent with such a mechanism. A mechanism in which receptors blocked by TEA can close would account for the experimental findings.

Capillary electrochromatography of tricyclic antidepressants on strong cation exchangers with different pore sizes

Four cation-exchange materials, possessing propanesulfonic acid ligands, for use in capillary electrochromatography were prepared from different commercially available 5-μm bare-silica particles ranging from 80 to 800 Å in pore size. The performance of the materials was investigated at different compositions of the mobile phase (pH, ionic strength, and acetonitrile content) using tricyclic antidepressants and related quaternary ammonium analogues as test analytes. The wide-pore materials promoted pore flow, but this had no positive influence on the performance. The small-pore (highest surface area) particles gave, as could be expected, the best selectivity.

Capillary electrochromatography of hydrophobic amines on continuous beds.

The capillary electrochromatographic separation performance of hydrophobic amines and a related quaternary ammonium compound on continuous beds based on polymers of acrylamide has been studied. The chromatographic bed is polymerized in situ and the character of the polymers with regard to hydrophobicity and charge has been systematically changed by regulating its content of isopropyl and sulfonate ligands, respectively. The best performance was obtained for columns with a molar ratio of 1:80 for the sulfonate and isopropyl groups, and resulted in efficiencies up to 200000 plates per meter. The effects on retention, resolution and elution order by ionic strength, pH, and content of acetonitrile in the mobile phase have been investigated. The quaternary ammonium compound was always the least retained irrespective of pH. By increasing the pH, a reversal of the migration order between the tertiary and secondary amine was obtained. The results indicate a complex migration/retention mechanism where ion-exchange, adsorption and electrophoretic mobilities play a role. The concentration limit of detection could be lowered from 1.3 microg/mL to 50 pg/mL by using a high content of 2-propanol (96%) in the sample compared to dissolving the analytes in the mobile phase.

ChemInform Abstract: Mannich Bases of Arylalicyclic Ketones and Related Quaternary Ammonium Compounds with Antileukemic Properties.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Thermodynamic Studies on the Cyclodextrin Complexation of Aromatic and Aliphatic Guests in Water and Water−Urea Mixtures. Experimental Evidence for the Interaction of Urea with Arene Surfaces

The thermodynamic functions that describe the complexation of a series of four carboxylic acid guests and two related quaternary ammonium derivatives with β-cyclodextrin were measured using flow calorimetry at 298 K in aqueous media in the presence and in the absence of large concentrations of urea. The relative differences of the thermodynamic parameters of complexation revealed the existence of specific interactions between urea and the aromatic surfaces of some of the nonpolar guests. As expected, the relative changes in the complex stability constants upon addition of urea have been found to depend on the balance of opposing enthalpic and entropic contributions. The interpretation as well as the magnitude of the interaction between urea and aromatic surfaces are in line with previous experimental and computational studies. The experimental evidence presented in this work provides insight into the mechanism by which large amounts of urea denature globular proteins in aqueous media.

Guest/Host Interactions in High Silica Zeolite Synthesis: [5.2.1.02.6]Tricyclodecanes as Template Molecule

Zeolite synthesis results for the use of a family of related quaternary ammonium derivatives of tricyclodecane hydrocarbons as structure-directing agents are described. The work continues our inter...

Biological Recognition of Enantiomeric Silanes: Syntheses and Antimuscarinic Properties of Optically Active (2-Aminoethyl)cyclohexyl(hydroxymethyl)phenylsilanes and Related Quaternary Ammonium Derivatives

Biological Recognition of Enantiomeric Silanes: Syntheses and Antimuscarinic Properties of Optically Active (2-Aminoethyl)cyclohexyl(hydroxymethyl)phenylsilanes and Related Quaternary Ammonium Derivatives

Cytotoxic Evaluation of Some 3,5-Diarylidene-4-piperidones and Various Related Quaternary Ammonium Compounds and Analogs

A number of 3,5-diarylidene-4-piperidones (1) and some related quaternary ammonium salts (5) as well as closely related analogs were prepared principally as candidate cytotoxic agents in two screens. The first test system used an average of 54 human tumor cell lines from eight neoplastic diseases, namely leukemia, melanoma, colon, non-small-cell lung, small-cell lung, central nervous system, ovarian, and renal cancers. Selective toxicity was demonstrated by some of the compounds, especially toward leukemia. The second screen used L 1210 lymphoid leukemia cells. In general, the compounds were less cytotoxic than the reference drug melphalan in both screens. Linear plots were made between the Hammett (σ), fragment (f), and molar refractivity (MR) constants of the nuclear substituents in series1and5with the IC50figures of both the human tumor cell lines and L 1210 cells. Evaluation against the human tumor cell lines revealed that increases in thefvalues were correlated with elevation of cytotoxicity in both series1and5; MR constants were also important in series5. In the L 1210 screen, σ and MR constants were positively correlated with cytotoxicity. X-ray crystallography was undertaken on 3,5-bis-[[4′-(methylthio)phenyl]methylene]-1-methyl-4-piperidone methiodide (5d), which had significant cytotoxicity, and 3,5-bis(4-pyridylmethylene)-1-methyl-4-piperidone methiodide (6), which was virtually inactive in both screens. A number of structural features were noted, and in particular a smaller interplanar angle made by one of the arylidene groups with the central piperidine ring in the case of5dthan either of the 4-pyridylmethylene moieties in6may contribute to the variation in cytotoxicity between these two compounds. Eleven compounds which were examined for activity against a panel of 12 viruses were shown to display only marginal potencies or to be inactive at the highest concentrations utilized. Two compounds with slight activity both had the hydrophilic carboxylate ion in the aryl rings. From this study, various conclusions pertaining to future molecular modification with a view to increasing cytotoxic potency were made.

Evaluation of some Mannich bases of cycloalkanones and related compounds for cytotoxic activity

A number of Mannich bases of cycloalkanones and related quaternary ammonium compounds were prepared for cytotoxic evaluation in order to examine the theory that sequential release of alkylating agents produces increased bioactivity compared to related compounds containing only 1 potential alkylating site. Many of the compounds had significant activity against murine L1210 cells and various human tumours. Some correlations between structure and activity were noted but the biological data did not support the view that potential sequential liberation of cytotoxic species produced compounds with increased potency. The formation of various oximes and oxime benzoates as candidate prodrugs was achieved but in general these compounds were not cytotoxic at the concentrations utilized. This observation may be due to the fact that the oximes were much more stable in deuterated phosphate buffered saline over a period of 48 h at 37°C than the Mannich bases, as revealed by 1H-NMR spectroscopy.

Carrier-mediated transport system for choline and its related quaternary ammonium compounds on rat intestinal brush-border membrane

The characteristics of the intestinal transport system for choline were investigated using isolated brush-border membrane vesicles from rat small intestine. In spite of the diminutive lipid solubility, the uptake of choline by membrane vesicles reflected smooth permeation into intravesicular space rather than the binding to the membrane surface. Physiological conditions, present in the intact intestine, such as an inward-directed Na + or H + gradient and inside negative membrane potentials, didn't directly involve in choline transport across the brush-border membrane. Moreover, an outward-directed H + gradient had no significant effect on the time course of choline transport. However, in the absence of a driving-force, the initial uptake of choline exhibited a saturable manner. A kinetic analysis of the initial uptake rate gave an apparent K m of 159 μM. Furthermore, unlabeled choline caused both cis-inhibition and trans-stimulation for labeled choline transport, suggesting the existence of a carrier-mediated transport system for choline, classified as so-called ‘facilitated diffusion’. Since tetramethylammonium, acetylcholine, and N 1-methylnicotinamide caused both cis-inhibition and trans-stimulation, they appear to be accepted as the substrate of choline carrier. On the other hand, quaternary ammonium compounds (QACs) such as those which possessed hydrophobic parts in their molecules exhibited only cis-inhibition. They also inhibited Na +-dependent d-glucose transport, indicating that they influenced various carrier-mediated transport systems non-specifically due to interaction with the membrane. These findings strongly suggest that the choline transport system on the brush-border membrane of rat intestine recognizes only small molecular QACs as its substrate.

Analysis of steroids : XLI. Ion-pair high-performance liquid chromatographic separation of quaternary ammonium steroids on silica

A normal-phase ion-pair chromatographic system has been developed for the high-performance liquid chromatographic investigation of pipecuronium bromide (2β,16β-bis(N′-dimethyl-1-piperazinyl)-3α, 17β-diacetoxy-tα-androstane dibromide) and related quaternary ammonium steroids. The use of silica as the stationary phase and a 96:4 mixture of acetonitrile and water containing 0.1 mol/dm 3 sodium perchlorate as the eluent with detection at 213 nm enable the potential impurities as well as the hydrolic and oxidative degradation products of pipecuronium bromide to be separated and detected down to the 0.01% level. The above system is also applicable to the high-performance liquid chromatographic investigation of other quanternary ammonium steroids (pancuronium bromide, vecuronium bromide).

ChemInform Abstract: Syntheses via Vinyl Sulfones. Part 35. SN2′ Addition of Organometallic Reagents to β′‐Amino Cyclohexenyl Sulfone Derivatives.

AbstractThe amino(siloxy)cyclohexenyl sulfone (X) and the related quaternary ammonium salt (XIII) are prepared as shown in the reaction scheme via cleavage of the oxirane (IV).

Mass spectrometry of pancuronium bromide and related quaternary ammonium steroids using the moving belt LC/MS interface

AbstractPancuronium and vecuronium are members of a series of quaternary ammonium steroids used as neuromuscular blocking agents in anesthesiology. In this study the mass spectrometric properties of these bromide salts are examined and spectral features which permit their differentiation are evaluated. The relative merits of chemical ionization and fast atom bombardment using the moving belt liquid chromatography/mass spectrometry interface have been investigated. Fragmentation pathways for both ionization methods were determined with deuterium labeling and linked‐scan techniques. Cleaner spectra can be obtained via the matrix‐free belt introduction system as compared to conventional fast atom bombardment.