Quinolinium Iodide Research Articles

Characterization of the Interaction of the Radioprotector 1-Methyl-2-[2-(Methylthio)-2-Piperidinovinyl]Quinolinium Iodide with Supercoiled DNA

The interaction of the radioprotector 1-methyl-2-[2-(methylthio)-2-piperidinovinyl]quinolinium iodide (VQ) with linear and supercoiled pIBI30 DNA was studied by flow linear dichroism spectroscopy, equilibrium dialysis, circular dichroism, and UV absorption spectroscopy. The negative linear dichroism spectra of VQ-DNA complexes throughout the 220-500 nm wavelength region, a red shift in the VQ main absorption band (at 452 nm) of 1-2 nm upon binding to DNA, and a concentration-dependent unwinding of supercoiled DNA suggest that the primary mode of interaction of VQ with DNA (at least at low concentrations) is intercalative in nature. A least-squares analysis of the equilibrium dialysis binding of VQ to supercoiled DNA using the McGhee-von Hippel equation gives an association constant K = 7300 +/- 300 M-1, and an exclusion number n in the range of 3.3-5.3. The lower value of n is obtained when effects of polyelectrolytes are also taken into account. Because quinolinium iodide derivatives with different substituents and DNA binding affinities can be synthesized, this family of compounds could be employed to probe relationships, if any, between radioprotective efficacy and DNA binding affinity.

Conformational plasticity of butyrylcholinesterase as revealed by high pressure experiments

The ligand binding and kinetic behaviour of butyrylcholinesterase (EC 3.1.1.8, acylcholine acylhydrolase) from human plasma was studied at 35 degrees C under high hydrostatic pressure. The binding of phenyltrimethylammonium was studied by affinity electrophoresis at various pressures ranging from 10(-3) to 2 kbar. The kinetics of enzyme carbamylation with N-methyl(7-dimethylcarbamoxy)quinolinium iodide was studied in single-turnover conditions up to 1.2 kbar using a high-pressure stopped-flow fluorimeter. Experiments were carried out in different media: 1 mM Tris-HCl (pH 8) with water, water containing 0.1 M lithium chloride and deuterium oxide as solvents. The volume changes (delta V and delta V++) associated with each process were determined from the pressure-dependence of the binding and kinetic constants. Kinetic data show that the binding of substrate to the enzyme leads to a pressure-sensitive enzyme conformational state which cannot accomplish the catalytic act. The pressure-induced inhibitory effect is highly cooperative; it depends on both the nature (charged or neutral) and the concentration of the substrate. Also, large solvent effects indicate that enzyme sensitivity to pressure depends on the solvent structure. This findings suggests that the substrate-dependent pressure effect is modulated by the solvation state of the enzyme.

Effects of CBDP and MEPQ on the toxicity and distribution of [3H]-soman in mice

Soman poisoning presents a problem in terms of its detailed pathophysiology and its detoxification mechanism(s). The present study was designed to evaluate the role of carboxylesterases (CaE) and cholinesterase (ChE) in the distribution and detoxification of soman in vivo. Mice were injected (i.v.) with 0.06-1.0 LD50 of [3H]-soman, 60 min following pretreatment with either 2-O-cresyl-4H-1:2:3 benzodioxa-phosphorine-2-oxide (CBDP), which blocks CaE or 7-(methylethoxyphosphinyloxy)-1-methyl quinolinium iodide (MEPQ), which selectively inhibits intravascular ChE. One hour after [3']-soman administration animals were sacrificed and whole body autoradiography was performed. High concentrations of [3H]-soman were found in lung and kidney in control mice, and low concentrations were found in central nervous system. Pretreatment with CBDP caused a 93% decrease in radioactive labelling in the lung, and a minor decrease in overall labelling, whereas pretreatment with MEPQ did not change the distribution pattern of [3H]-soman. It is concluded that lung is a major target organ for soman detoxification and that it exerts this effect by means of enzymatic reaction with soman through the abundant amounts of CaE which are present in the lung. Intravascular ChE has little (if any) effect on the distribution and detoxification of soman in vivo.

ChemInform Abstract: Thermal Dealkylations of Quaternized Methoxyquinolinium and Methoxyisoquinolinium Iodides in the Mass Spectrometer.

Dealkylations of N-alkyl 6- and 7-methoxy quinolinium and isoquinolinium iodides in the mass spectrometer proceeded to give predominantly O-demethylation when resonance stabilized ions were produced. When O-demethylation did not provide a resonance stabilized ion, N-dealkylation predominated.

Immunopharmacological actions of lumin (I): Anti-allergic actions of lumin

We used lumin (4,4'-(3[2(1-ethyl-4-(1-H)quinolidene) ethylidene]) propenylene [bis(1-ethyl quinolinium iodide)]) as a photosensitive cyanin dye and studied its effects on various allergic reactions. We obtained the following results: Lumin slightly inhibited the production of IgE antibody, but showed no effect on the production of IgM and IgG antibodies. Lumin slightly inhibited homologous rat PCA at 48 hr. It also showed some inhibitory activity against histamine (His) release caused by in vitro antigen-antibody reaction. Lumin significantly inhibited the acceleration of the delayed-type hypersensitivity (DTH) reaction by cyclophosphamide (CY). The above results suggest that lumin shows anti-allergic activity through the mediation of immunopharmacological activity.

A quaternary anti-cholinesterase probe for determining the integrity of the blood - brain barrier

7-(Methylethoxyphosphinyloxy)-1-methyl quinolinium iodide (MEPQ), a new quaternary anti-cholinesterase (anti-ChE) compound was prepared and evaluated as a potential probe for assessing changes in the blood-brain barrier (B-BB) permeability. MEPQ was found to be 170 times more potent in its cholinesterase inhibitory activity than phospholine iodide, a previously reported anti-ChE probe in B-BB research. In rats and mice with impaired B-BB induced by osmotic opening, MEPQ readily penetrated through the damaged site as demonstrated by considerable reduction of ChE activity. In controls, brain ChE activity remained unaffected. It is suggested that MEPQ is a useful probe for both qualitative (histological staining) and quantitative (brain homogenated) assessment of permeability changes in the B-BB.

Merocyanine dyes from 4‐dicyanomethylene‐2,6‐dimethyl‐4H‐pyran

AbstractNeutral dyes were prepared by reacting 1‐ethyl‐2[2‐(N‐methylanilino)vinyl]quinolinium iodide with 4‐dicyanomethylene‐2,6‐dimethyl‐4H‐pyran and then condensing the resulting product with an aromatic aldehyde.

Medium Effect on the Ionisation Constants of Some Hydroxy Derivatives of 1-Ethyl-2-styrylpyridinium and -quinolinium Iodides

Abstract The pKa values of 1-ethyl-2-(4 or 2-hydroxystyryl)pyridinium and -quinolinium iodides in different organic solvent–water mixtures were determined. The organic solvents used are methanol, ethanol, acetone, DMF and DMSO. The ionisation of the compounds under investigation depends largely on both the proportion and the nature of the organic co-solvent used. The ionisation constant decreases with increase in the proportion of the organic co-solvent in the medium. The major important effect responsible for this is the difference in the stabilization of base by donor hydrogen bond from solvent molecules. The free energy of solvation of both acid and proton by electrostatic interaction and that of the base by donor hydrogen bond from solvent molecules were calculated. The effect of the molecular structure of the compound on pKa is also discussed.

Equilibrium and kinetic studies of the interaction of site-specific ligands with acetylcholinesterase from Electrophorus electricus.

The interactions of edrophonium chloride, gallamine triiodide, and propidium diiodide with affinity-purified acetylcholinesterase from Electrophorus electricus have been examined under conditions of low ionic strength (0.001 M Tris, pH 8.0) using kinetic and fluorescence titration techniques. Edrophonium is a competitive inhibitor of the steady-state hydrolysis of acetylthiocholine, with an inhibition constant, Kcomp, of 1.2 × 10−8 M. Double reciprocal plots in the presence of either gallamine or propidium are nonlinear. Similarly, the pre-steady-state carbamoylation of the enzyme by 7-(dimethylcarbamoyloxy)-N-methyl quinolinium iodide is competitively inhibited by edrophonium, whereas the intercepts of the double reciprocal plots of pseudo-first-order rate constant of carbamoylation versus substrate concentration are displaced downwards in the presence of gallamine or propidium. These results, and those of equilibrium binding studies utilizing the fluorescence properties of bound propidium, suggest that gallamine and propidium compete for a peripheral class of anionic sites on the enzyme, whereas edrophonium binds to the anionic subsite of the catalytic site. The characteristics of propidium binding to the eel enzyme differ from those previously observed with enzyme isolated from Torpedo californica. Whereas the tetrameric Torpedo enzyme possesses four binding sites of equal affinity for propidium, the eel enzyme appears to have two classes of propidium binding site. One set of approximately two sites per tetramer is characterized by a dissociation constant of approximately 2–5 × 10−8 M; a second set of two sites bind propidium with a dissociation constant of 4 × 10−6 M. Possible reasons for these differences are discussed.

ChemInform Abstract: SYNTHESIS OF MEROCYANINE DYES

AbstractAus den Komponenten (I) und (IIIa) bzw. (IV) + (IIIa), (IIIb) bzw. (IV) + (VI) werden die neuen Titelverbindungen (II), (V) und (VII) synthetisiert (IR‐, UV‐Daten).

Synthesis of Merocyanine Dyes

Abstract New 1-ethyl-2-[(2-substituted 3-oxoisoindolin-1-ylidene)methyl]-pyridinium or quinolinium iodide merocyanine dyes were obtained by the reaction of 2-methyl quaternary salts with N-substituted phthalimide in the presence of piperidine. 1-Ethyl-2-[(1-substituted 5-oxo-3-pyrrolin-2-ylidene)methyl] quinolinium iodide merocyanines were also prepared. Structural configuration of the synthesised compounds was confirmed by IR and UV spectral determination. 1-Ethyl-2-[[3-oxo-2-(4-phenylthiazol-2-yl)isoindolin-1-ylidene]methyl]quinolinium iodide has high bactericidal activity againsist E.Coli, Staphylococcus Aureus, and Staphylococcus Albas.

Comparison of atypical and usual human serum cholinesterase. Purification, number of active sites, substrate affinity, and turnover number.

Atypical and usual human serum cholinesterases were purified and studied with the fluorescent probe, N-methyl-(7-dimethylcarbamoxy)quinolinium iodide. Four active sites per tetramer were found in each enzyme. The turnover numbers of usual and atypical cholinesterases were the same: 15,000 mumol of benzoylcholine hydrolyzed/min/mumol of active site; 48,000 min-1 for o-nitrophenylbutyrate; and 0.0025 min-1 for N-methyl-(7-dimethylcarbamoxy)quinolinium iodide. They had identical rate constants for carbamylation, (5.0 min-1) and for decarbamylation (0.15 h-1). The major difference between the two genetically determined forms of the enzyme was substrate affinity, KD being 0.16 mM for usual and 5.4 mM for atypical cholinesterase, for the fluorescent probe substrate. Km for the uncharged ester, o-nitrophenylbutyrate, was 0.14 mM for both enzymes, whereas Km for benzoylcholine was 0.005 mM for usual and 0.024 mM for atypical cholinesterase. We interpret these data to mean that the two enzymes differ only in the structure of their anionic site.

Light Absorption in N-Acetonyl Quinolinium Iodide

The absorption spectra of N-acetonyl quinolinium iodide in different solvents have been studied in the region 200 nm-1100 nm. Four bands have been observed in DMF, methanol, water and alkaline water. The bands have been assigned to different intramolecular transitions.

Some substitution reactions of thieno[3,2-f]quinoline

Mononitration, monobromination, and Friedel–Crafts acylation of thieno[3,2-f]quinoline occurred in the 2-position; dibromination in concentrated sulphuric acid gave the 1,2-dibromo-derivative. The Hunsdiecker reaction of thieno[3,2-f]quinoline-2-carboxylic acid gave a mixture of 1,2,5-tribromothieno[3,2-f]quinoline and 5-bromothieno[3,2-f]quinoline-2-carboxylic acid in addition to unchanged starting material. Bromination of sodium thieno[3,2-f]quinoline-2-carboxylate gave the 5-bromo-acid. N-methylthieno[3,2-f]quinolinium hydrogen sulphate was oxidised to N-methylthieno[3,2-f]quinolin-7-one, which, on treatment with phosphorus pentachloride, gave 7-chlorothieno[3,2-f]quinoline. However, the methosulphate reacted with aqueous potassium cyanide to give 6,9-dihydro-N-methylthieno[3,2-f]quinoline-9-carbonitrile which when oxidised with iodine in pyridine yielded 9-cyano-N-methylthieno[3,2-f]quinolinium iodide. Demethylation gave thieno [3,2-f]quinoline-9-carbonitrile. The Reissert compound derived from thieno[3,2-f]quinoline reacted with phosphorus pentachloride to yield thieno[3,2-f]quinoline-7-carbonitrile, which on hydrolysis with concentrated hydrochloric acid yielded the 7-carboxylic acid. This was methylated with diazomethane to give methyl thieno[3,2-f]quinoline-7-carboxylate. The assignment of these structures has been confirmed whenever possible by conversion of the compounds into known compounds and comparison with authentic samples, or is derived from a study of the relevant 1H n.m.r. spectra.