Quaternary Ammonium Derivatives Research Articles

A new quaternary ammonium compound with plant growth regulatory activity

Of several quaternary ammonium derivatives tested, 1-allyl-1-(3,7-dimethyloctyl)piperidinium bromide showed the best growth-retarding activity. OnChrysanthemum morifolium the growth retardation obtained with a single application of 100–200 ppm compared favourably with that obtained from 2–3 applications of 3400 ppm of N-dimethylaminosuccinamic acid (daminozide).

Chlorpromazine Metabolism IV: Quaternization as a Key to Determination of Picomoles of Chlorpromazine and Other Tertiary Amine Drugs

Reaction of chlorpromazine with 9‐bromomethylacridine under appropriate conditions yields a nonfluorescent quaternary ammonium derivative which, on subsequent photolysis, liberates fluorescence. The major component of this fluorescence is 9‐methylacridine (86%), while two minor components are 9‐acridinecarboxaldehyde (6%) and 9‐acridinemethanol (8%). The mechanism of photolysis leading to formation of these products appears to involve homolytic as well as heterolytic cleavages of the quaternary salt. Both the quaternization and the photolysis are stoichiometric. Appropriate isolation of the fluorescence and its quantitative determination constitutes the basis of a new and highly sensitive assay applicable to chlorpromazine and other tertiary amine drugs.

The action of bicuculline upon acetylcholine-induced excitations of central neurones

The electrophoretic application of a quaternary ammonium derivative of bicuculline to single neurones in amounts adequate to prevent their inhibition by GABA delivered from another barrel of the electrode assembly, causes a marked enhancement of the excitation of the cells induced by acetylcholine. This effect is consistent with the report that bicuculline is active as an anticholinesterase.

Syntheses and Plant Growth Retardant Activities of Quaternary Ammonium Compounds Derived from α-Ionone and Isophorone

To examine structure-activity relationships as plant growth retardants, a number of quaternary ammonium derivatives were prepared starting with α-ionone and isophorone. These were bioassayed using rice, cucumber and tomato seedlings.

Oximes of azolecarbaldehydes and ?2-azoline-carbaldehydes and their derivatives

The configurational (kinetic) stability of the anionic and zwitterionic forms of 1-methylpyrazolecarbaldehyde oximes and 1-methylimidazolecarbaldehyde oximes and their quaternary ammonium derivatives in aqueous solutions has been established. In an acid medium, isomerization takes place and an E-Z equilibrium of the cations of the oximes is established. The changes in the relative thermodynamic stabilities of the stereoisomers of the heteroaromatic carbaldehyde oximes as functions of the size and nature of the ring, the position of the oxime group, and the steric loading are due to spatial factors and electrostatic interactions. To substantiate the preferred conformations of the Z aldehyde oximes the differences in the values of the chemical shifts of the α protons of the ring and the rates of their deuterium exchange have been used.

Azole- and ?2-azolinecarbaldehyde oximes and their derivatives

The production of 1-methyl-substituted pyrazole-, imidazole-, δ2-pyrazoline-, and δ2-imidazolinecarbaldehyde oximes is described. The alkylation of 1-methylimidazole-and 1-methyl-δ2-pyrazolinecarbaldehyde oximes with methyl iodide and α,Ω-dihalo-genoalkanes forms quaternary and bisquaternary ammonium derivatives, respectively. The quaternary derivatives of 1-methylpyrazolecarbaldehyde oximes are obtained by the oximation of the corresponding quaternary derivatives of the aldehydes; the direct methylation of these oximes either does not take place or leads to the formation of nitrones.

Synthesis and curare-like properties of quaternary ammonium derivatives of cyclic acetals of levulinaldehyde and levulinic acid

Synthesis and curare-like properties of quaternary ammonium derivatives of cyclic acetals of levulinaldehyde and levulinic acid

Long-Term Growth-Retardant Effects of (+)-Limonene Derivatives on Citrus1

Abstract The growth-retardant effects of succinic acid-2,2-dimethylhydrazide (SADH), 1 n-alkyl and 2 benzyl quaternary ammonium derivatives of (+)-limonene were determined after application of 2 foliar sprays on young grapefruit (Citrus paradisi Macf.) seedlings which were subsequently pruned to remove all growth. Only the n-alkyl derivative, l-p-menthanol-2-dimethylamino heptyl bromide (Q-58), caused dwarfing and marked internode shortening of new growth on all treated plants 71 days after the second foliar spray. A similar experiment on a larger scale using Q-58 and 2 new n-alkyl derivatives of (+)-limonene produced retardation of new growth for 136 days after the second foliar spray. However, true dwarfing was only apparent in a few of the treated seedlings. These results indicate that n-alkyl quaternary ammonium derivatives of (+)-limonene are stored in the roots or lower stems of grapefruit seedlings and can continue to retard terminal shoot development for about 4 months after treatment.

Metabolism of quaternary ammonium compoundS-I: Binding of tropane alkaloids to rat liver lysosomes

After intravenous injection of three quaternary ammonium derivatives of tropane alkaloid, tritiated p-biphenylmethyl-( dl-tropyl- α-tropinium) bromide ( 3HBTTB), azoniaspiro-(3α-benziloyloxynortropane-8,1-pyrrolidine) chloride ( 3H-ABPC) and 14C-labeled N-methylhyoscine methylsulfate ( 14C-MHM), intracellular distribution of radioactivity was investigated in the liver of rats. Subcellular distribution of 3HBTTB was found to correspond reasonably well to that of acid phosphatase activity, a marker enzyme of lysosomes. The other two drugs were also specific to the light mitochondrial fraction on subcellular distribution. The bulk of the radioactivity in the light mitochondrial fraction was observed to bind to a particulate fraction corresponding in density to the lysosomes. It was found that 3H-BTTB presented in the low density lysosomes of the liver of rats after treatment with RR-2020, a non-ionic detergent, and that the radioactivity bound to the light mitochondrial fraction was solubilized to some extent by the addition in vitro of nonradioactive drugs. These data indicated that the presence of these drugs in the light mitochondrial fraction was due to binding to lysosomal membranes.

Inhibition of choline acetyltransferase by 2-dimethylaminoethyl chloroacetate and related compounds.

A number of cyclic quaternary ammonium derivatives structurally related to acetylcholine were tested for their inhibitory effect on choline acetyltransferase in vitro. They had no effect. The alcohol derivatives in this series of compounds were not acetylated by the enzyme. The tertiary amine 2‐dimethylaminoethyl chloroacetate and a few related compounds had inhibitory activity in vitro. 2‐Dimethylaminoethyl chloroacetate was the most active of these compounds, being about half as potent as the quaternary derivative choline chloroacetate. It inhibited the enzyme uncompetitively with regard to choline as well as acetyl‐CoA, the Ki values being 1.2 × 10‐4 M (choline) and 4 × 10‐5 M (acetyl‐CoA) under the conditions used. 2‐Dimethylaminoethyl chloroacetate and two of the other active compounds had no effect in high doses on the acetylcholine level in the mouse brain in vivo.

Isolation of kopsinilamine from Vinca erecta

1. The new alkaloid kopsinilamine has been isolated from the epigeal part ofV. erecta. 2. A study of chemical properties and spectra has shown that kopsinilamine is a quaternary ammonium derivative of kopsinilam.

Formation of a piperidinium derivative from N-(5'-chloropentyl)-N-methylaminoaceto-2,6-xylidide in relation to the sustained local anaesthetic action on the sciatic nerve of the guinea-pig in vivo.

THE possibility of using the intramolecular alkylation reaction of tertiary ω-haloalkylamines (Fig. 1) to overcome the cell membrane barrier to cyclic quaternary ammonium compounds seems to have been almost entirely overlooked. Some pharmacological applications of this principle have already been studied1–3 and we feel that the possibility of obtaining local anaesthetic agents4 may be of therapeutic interest. The nerve sheaths and membranes hinder the penetration of quaternary ammonium compounds5, but tertiary amines in their base form are able to pass6. Thus, a tertiary haloalkylamine (I in Fig. 1) should be able to cross the barriers, and, because of its capacity to cyclize, the corresponding cyclic quaternary ammonium derivative (II) would be expected to be formed at least to some extent at the sites for blockade of nerve excitation. The barriers to outward diffusion of the quaternary compound formed are probably the same as for the inward movement, so that very slow disappearance can be expected. Accordingly, if the quaternary derivative has a local anaesthetic action, this would probably be of long duration. Our observation that tertiary haloalkylamine derivatives closely related to lidocaine have a long term anaesthetic effect4 supports this hypothesis. It would be valuable, however, to try to relate the local Q XCH3 JH3 -NHCOCH2N(CH2)5CI VCH3 I 'CH3 jJrX . -NHC0CH2N 4-Ct CH3 *˜ II anaesthetic effect in vivo with the amount of (I) and of the piperidinium derivative (II) formed in the nerves. One compound, N-(5 '-chloropentyl)-N-methylaminoaceto-2,6-xyli-dide (I in Fig. 1), tritium-labelled in the 1'-position (specific activity 10 mCi/mmol), was therefore selected for the following experiments.

Effect of phenyl substitutents in benzyl quaternary ammonium derivatives of (+)-limonene on plant growth-retardant activity

Effect of phenyl substitutents in benzyl quaternary ammonium derivatives of (+)-limonene on plant growth-retardant activity

The effect of quaternary ammonium derivatives of bile acids on the rate of swelling of Pseudomonas aeruginosa in solutions of sodium and potassium salts.

Quaternary ammonium derivatives of bile acids increase the rate of swelling of washed cells of Pseudomonas aeruginosa incubated in solutions of potassium phosphate and to a lesser extent in solutions of sodium phosphate. The enhanced swelling is proportional to the concentration of the compounds in potassium but not in sodium solutions. The reason for this is that sodium but not potassium can displace the compounds from their attachment to the cell site(s) and the interaction is mixed competitive noncompetitive. Both cations, however, when added to cells before the compounds inhibit their effect. Formaldehyde-treated cells behave essentially in the same way as normal cells, which indicates that the compounds are not inhibiting metabolic pumps but are facilitating diffusion of the ions. As the steroid portion of the molecule becomes less lipophilic by the introduction of hydroxyl groups their activity decreases.

Autoradiographic studies on the distribution of drugs. I. Distribution of 14C-anisotropine methbromide in mice.

The distribution of 14C-anisotropine methbromide, a quaternary ammonium derivative of atropine, was studied in mice by whole-body autoradiographic technique. After i. p. and s. c. injections, the radioactivity was found to be mainly concentrated in the excretory organs : the liver, kidney, gall and urinary bladders, gastrointestinal tract and salivary gland, indicating a rapid excertion of the drug via both the urinary and biliary routes. In addition, the radioactivity was found to be accumulated specifically in the pancreas, gastric mucosa, walls of the spermatic and oviducts and uterus. Almost no accumulation was observed in the central nervous system, the muscular tissues and the endocrine organs. Autoradiography in mice of which the common bile duct was ligated prior to the injection showed an occurrence of a glandular secretion of the drug into the intestinal mucosa from the blood circulation. After oral administration, the radioactivity was found to be restricted very effectively to the gastrointestinal tract, indicating a limited absorption from the intestine, and the most part of the absorbed drug to be cleared back into the intestinal tract via the bile. These characteristics are discussed with respect to the structural characteristic of quaternary ammonium structure and the possible relations are pointed out between the sites of the drug accumulation and those of the pharmacological action where the drug has been clinically applied as a peripheral anti-spasmodic agent with a lower side effect than has atropine.

The Biological Activity of Vinyl and Butenyl Sulfone Derivatives

AbstractMono‐ and bifunctional amino‐ and quaternary ammonium derivatives of ethyl‐ and butenylsulfones have been prepared, and preliminary results on their biological activity are reported.

Quaternary ammonium derivatives of cholesterol

Quaternary ammonium derivatives of cholesterol

Growth Retardation of Citrus by Quaternary Ammonium Derivatives of (+)-Limonene1

Abstract The growth-retardant activity of 4 quaternary ammonium derivatives of (+)-limonene was determined by application of foliar sprays on greenhouse-grown grapefruit seedlings. The most active compound was 1-p-men-thanol-2-dimethylamino heptyl bromide. The 3,4-dichlorobenzyl chloride and p-methylbenzyl chloride quaternary ammonium derivatives of 2-dimethylamino-1-p-menthanol were occasionally rated as highly active, but in some tests these compounds were either only slightly active as growth retardants or moderately active as growth stimulators. The 2,4-dichlorobenzyl chloride derivative was only moderately active on grapefruit seedlings. Alar in some tests was moderately effective as a growth retardant, and in other tests it was either inactive or somewhat active as a growth stimulator. The heptyl derivative at 3000 and 6000 ppm was also effective in reducing growth of 3-year-old field-grown lemon trees for a relatively short period of time. A 1000 ppm application appeared to stimulate growth of lemon trees and grapefruit seedlings.

Über die Stereochemie der Hydrogenolyse von N‐Benzyl‐Bindungen I. Die Hydrogenolyse von Derivaten der 2‐Amino‐2‐phenyl‐propionsäure.

AbstractThe stereochemistry of the hydrogenolysis of benzyl‐N bonds was studied using S(+)‐2‐dimethylamino‐2‐phenyl‐propionic acid (I) and its derivatives, and R(−)‐2‐anilino‐2‐phenyl‐propionic acid (II). The configuration of I was confirmed, that of II established by ORD. measurements, after transformation of the phenyl into cyclohexyl groups. On a palladium catalyst the hydrogenolysis of I, its methyl and ethyl esters and its amide proceeded with 72 to 99% inversion of configuration, that of II with at least 66% inversion. The ester of the quaternary ammonium derivative of I gave as much inversion as retention (= racemisation).

Correlation of Pseudocholinesterase Inhibition and Plant Growth Retardation by Quaternary Ammonium Derivatives of (+)-Limonene

THE terpene hydrocarbon (+)-limonene is widely distributed in nature and comprises more than 95 per cent of distilled citrus peel oils. As part of a study of limonene derivatives having possible biological activity, I reported the synthesis of a number of quaternary ammonium compounds which are plant growth retardants1,2. Several of these derivatives also inhibited human blood serum (pseudo) cholinesterase in tests for drug activity (my unpublished results). Here I report the discovery of a direct correlation between serum cholinesterase inhibition by these compounds and their ability to retard plant growth.