Quaternary Trimethylammonium Research Articles

Experimental studies on drag reduction and rheology of mixed cationic surfactants with different alkyl chain lengths

Experimental studies of the effects of mixtures of cationic surfactants on their drag reduction and rheological behaviors are reported. Cationic alkyl trimethyl quaternary ammonium surfactants with alkyl chain lengths of C12 and C22 were mixed at different molar ratios (total surfactant concentrations were kept at 5 mM with 12.5 mM sodium salicylate (NaSal) as counterion). Drag reduction tests showed that by adding 10% (mol) of C12, the effective drag reduction range expanded to 4–120 °C, compared with 80–130 °C with only the C22 surfactant. Thus mixing cationic surfactants with different alkyl chain lengths is an effective way of tuning the drag reduction temperature range. Cryo-TEM micrographs revealed thread-like micellar networks for surfactant solutions in the drag reducing temperature range, while vesicles were the dominant microstructures at non-drag reducing temperatures. High extensional viscosity was the main rheological feature for all solutions except 50% C12 (mol) solution, which also does not show strong viscoelasticity. It is not clear why this low extensional viscosity solution with relatively weak viscoelasticity is a good drag reducer.

Utilization Of Tetrabutylammonium Triphenyldifluorosilicate (TBAT) In The Synthesis of 6-Fluoropurine Nucleosides

Tetrabutylammonium triphenydifluorosilicate (TBAT) has been found to be a useful reagent for the conversion of 6-chloropurine nucleosides to 6-fluoropurine derivatives. The 6-chloropurine nucleosides were reacted with trimethylamine to form quaternary trimethylammonium salts which were treated in situ with TBAT in DMF to effect conversion to the 6-fluoro derivatives in yields of 59–72%.

Multiple Cation-π Interactions between the Trimethylammonium Moiety and the Aromatic Rings within a Molecular Complex Formed between 3-Phenylpropionic Acid Choline Ester and Resorcin[4]arene

Abstract X-ray analysis of the molecular complex formed between 3-phenylpropionic acid choline ester (1) and tetraethylresorcin[4]arene (2) has shown that the choline ester 1 is captured by the bowl-shaped 2 through multiple cation-π interactions between the quaternary trimethylammonium group of 1 and the aromatic rings of 2 and that 1 itself forms a folded structure to make close contacts between its trimethylammonium moiety and the phenyl ring through cation-π interactions.

Cation-? interaction between the trimethylammonium moiety and the aromatic ring within lndole-3-acetic acid choline ester, a model compound for molecular recognition between acetylcholine and its esterase: an X-ray study

X-Ray analysis of indole-3-acetic acid choline ester, a model compound for molecular recognition between the neurotransmitter acetylcholine and its esterase, shows that the quaternary trimethylammonium group is folded back to make a close contact with the indole ring through the cation–π interaction; 1H NMR spectroscopy confirms this type of interaction also occurs in solution.

Effect of local anaesthetics on steroid-nicotinic acetylcholine receptor interactions in native membranes of Torpedo marmorata electric organ

Interactions between steroids and the nicotinic acetylcholine receptor (AChR) have been studied in native membrane vesicles from Torpedo marmorata electric organ by electron spin resonance (ESR) and fluorescence techniques. ESR spectra of spin-labelled cholestane (CSL) revealed that this steroid probe was incorporated into the AChR-rich membrane vesicles in regions which were to a certain extent enriched preferentially in the steroid, both in the presence and in the absence of local anaesthetics. Since the nitroxide group present in CSL is also a paramagnetic quencher of the intrinsic protein fluorescence, this property was used to characterize the AChR-steroid interactions. The quenching induced by CSL was sensitive both to AChR concentration and to the action of cholinergic agonists. In competition experiments, the ability of CSL to quench the AChR intrinsic fluorescence was markedly inhibited by benzocaine, tetracaine and QX-222 (a quaternary trimethylammonium derivative of lidocaine), and was totally inhibited by procaine. The effectiveness of local anaesthetics in inhibiting CSL-induced quenching followed the order: procaine ⪢ benzocaine ⪆ tetracaine > QX-222 . This inhibition effect was shown not to be charge-dependent. The data can be interpreted in terms of a model requiring specific association sites for local anaesthetics on the hydrophobic surface of the AChR which at least partially overlap with those for steroids.

Effects of chain‐length and unsaturation on affinity and selectivity at muscarinic receptors

1. Lengthening the chain in diphenylacetylcholine decreases affinity for muscarinic cholinoceptors in guinea-pig ileum. Diphenylacetoxypropyldimethylamine and its quaternary trimethylammonium salt are roughly equiactive: the dimethylamine and the piperidine have some selectivity for ileum compared with atria, but are not as active nor as selective as 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methobromide (MeBr). With the weaker diphenylacetoxybutyl compounds the base is more active than the quaternary salt. 2. The diphenylacetoxybutyl-, cis-butenyl and trans-butenyl compounds have similar affinities. The quaternary salts are less active than the tertiary bases, but they are less selective than the butynyl analogues studied in earlier work. 3. 1,1-Diphenyl-1-hydroxy-2,4-hexadiynyl dimethylamine and its trimethylammonium salt are inactive in concentrations below 100 microM, as are the (+)-camphor-sulphonyl ester of 4-hydroxy-N-methyl piperidine and its methiodide. The (+/-)-phenylcyclopentylacetyl ester of 4-hydroxy-N-methylpiperidine methobromide is more active than its cyclohexyl analogue and than 4-DAMP MeBr but it is less selective than 4-DAMP MeBr. 4. The high selectivity of p-fluoro-hexahydrosila-diphenidol is confirmed but this compound has relatively low affinity (for ileum log K = 7.8). 5. The results indicate steric constraints to binding at muscarinic receptors which could be used to check molecular modelling of the receptor based on its known amino acid sequence. The group binding the charged nitrogen is probably at the mouth of a cavity which can accommodate two large rings (as in 4-DAMP MeBr) but with a depth less than about 7 A so that the rod-like hexadiynes cannot fit. Differences between types of receptor may only involve small changes in geometry secondary to differences in amino acids not directly involved in binding and the production of selectivity depends upon finding substituents which interfere with binding more at one type of receptor than at another.

Interaction of quaternary ammonium compounds with acetylcholinesterase: characterization of the active site

The relation of the structure of 31 quaternary ammonium compounds (28 inhibitors; 3 substrate analogues) with their effects on the activity of acetylcholinesterase (EC 3.1.1.7; AChE) was studied. The compounds were structurally related to the natural substrate acetylcholine (ACh). All bear a trimethylammonium moiety as cationic head. The inhibitors include a variety of functional groups instead of an electrophilic ester group, making these substances suitable to probe the esteratic subsite. The inhibition constants and K m values were determined in kinetic experiments under steady state conditions (pH-stat method). Most of the substances acted as reversible, competitive inhibitors with K I in the range of 10 −6−10 −3 M. The substrate analogues had K m values between (1.2–2.2) × 10 −4 M. The data allow the following main conclusions: (1) The quaternary trimethylammonium group of ACh is of high importance for substrate binding to AChE. It mediates association at the anionic site. (2) A poorer contribution to binding (two orders of magnitude lower) is attributable to the apolar methylene chain in ACh. It can be related to a hydrophobic interaction of the hydrocarbon chain at a region neighbouring the anionic site. (3) The ester group (both C=O and O) does not contribute to substrate binding. It is only responsible for reactivity.

Modified anion-exchange resins for improved chromate selectivity and increased efficiency of regeneration

Experimental results are provided to show that a modified strong-base resin with tripropyl quaternary ammonium functionality offers greater chromate selectivity and improved efficiency of regeneration over widely used commercially available anion-exchange resins with trimethyl quaternary ammonium or dimethyl tertiary amine functionality. Use of this new, modified resin is likely to be more economic for decontaminating chromate-laden industrial wastewaters.

Aqueous Infrared Pharmaceutical Analysis of Two Choline Compounds by Flow Injection Analysis Using the CIRCLE Cell

The advent of the cylindrical internal reflectance (CIRCLE) cell has solved the difficult problem of quantitation of solutes in aqueous solutions by infrared spectroscopy. By a combination of flow injection analysis (FIA) and Fourier transform infrared (FT-IR) spectroscopy with the CIRCLE cell, a fast, reproducible technique suited for the determination of two choline compounds of pharmaceutical interest—succinylcholine chloride and bethanechol chloride—was developed. Quantitation was carried out with the use of either the ester band at 1075 cm−1 for bethanechol or the trimethyl quaternary ammonium band at 953 cm−1 for succinylcholine. Linearity of standard solutions was achieved from about 0.5 to at least 50 ppt for both compounds, and detection limits of 0.02% w/v were possible. A sample throughput of 60 samples/h was estimated. Analysis of pharmaceutical preparations was performed after minor sample clean-up, which was necessary only in the case of the bethanechol chloride tablets.

ChemInform Abstract: SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF REDUCED DIASTEREOISOMERIC AND QUATERNARY AMMONIUM DERIVATIVES OF CALCIUM ANTAGONISTIC (METHYLENEDIOXY)INDENES ON THE ISOLATED RAT AORTA

AbstractDurch Hydrierung der Indene (I) erhält man in 98%iger Ausbeute Gemische der Indane (II) und (III).

Synthesis and pharmacological evaluation of reduced diastereoisomeric and quaternary ammonium derivatives of calcium antagonistic (methylenedioxy)indenes on the isolated rat aorta.

Based upon findings that 2-n-propyl- and 2-n-butyl-3-(diethylamino)-5,6-(methylenedioxy)indenes (1 and 2) inhibit a variety of calcium-activated cellular processes, it has previously been proposed that these compounds act as calcium antagonists with an intracellular site of action. In the present investigation, the diastereoisomeric dihydro analogues, cis- and trans-2-n-propyl- and cis- and trans-2-n-butyl-1-(dimethylamino)-5,6-(methylenedioxy)indans (5--8), and the trimethyl quaternary ammonium analogues of the unsaturated (3 and 4) and cis-saturated (9 and 10) systems were synthesized, and the ability of each to reverse norepinephrine- or KCl-induced contraction of the rat aorta was assessed. Saturation of 1 or 2 to produce the corresponding cis-aminoindan analogues (5 and 7) yielded compounds of similar spasmolytic activity, while saturation which yielded the respective trans forms (6 and 8) resulted in significant loss of potency. Methylation of either the cis unsaturated or saturated compounds to yield their respective quaternary derivatives also significantly reduced the potency of each compound. The reduced activity of the quaternary derivatives might be anticipated because of the limited cellular penetration of such compounds and is taken as evidence that the active tertiary analogues have an intracellular site of action. However, the results of the present investigation do not preclude the contribution of membrane effects to the pharmacological activity of the tertiary compounds (1, 2, 5, and 7), since the spasmolytically active analogues demonstrated a somewhat greater antagonistic potency against KCl-induced contractions as compared to their antagonism of the effects of norepinephrine.

ASSIGNING A BIOLOGICAL ROLE TO HYPAPHORINE AND LYCINE (TWO BETAINES)

The growth regulating activity of two betaines, hypaphorine and lycine, has been investigated through their action on different bioassays in comparison with the effects of indolylacrylic acid. This leads to include betaines in a larger group of naturally active compounds characterized by the onium (quaternary trimethyl-ammonium) ion, which can be compared to the synthetic quaternary ammonium containing growth retardants.

The ionization of phenolic amines, including apomorphine, dopamine and catecholamines and an assessment of zwitterion constants.

The dissociation constants of many phenolic amines, including benzylamines, phenethylamines, phenylethanolamines, phenylpropylamines, catecholamines, and apomorphine have been measured by potentiometric titration at 25 degrees C. Measurements have also been made with many of their methoxy derivatives and with series of phenolic quaternary ammonium salts. Some compounds were also studied at 37 degrees C. 2 Usually at least five titrations were made with each compound and Debye--Hückel theory was applied to convert concentrations to activities but the estimates of pKa were not constant and found to increase with increasing concentration. The range studied was usually 5-15 mM and a least-squares line-fit, based on the empirical assumption that pKa varies with (concentration)1/2, has been used to calculate values for 10 mM solutions and to extrapolate to infinite dilution and to 100 mM. The dependence of pKa on concentration was much less at 37 degrees C than at 25 degrees C. 3 At 37 degrees C the pKa values of many biologically interesting compounds in the group, dopamine, noradrenaline, adrenaline and isoprenaline, coryneine (the trimethylammonium derivative of dopamine) and apomorphine are within 1 log unit of physiological pH, indicating the presence of a significant proportion of either the zwitterion or of the uncharged phenolic amine. 4 Zwitterion constants have been estimated from the pKa values of the phenolic amines and those of their methoxy and quaternary trimethylammonium analogues. Zwitterion formation does not appear to be associated with activity at alpha-adrenoceptors and probably not with activity at beta-receptors. The active species seems likely to contain the unionised phenolic group but at dopamine receptors this may be in the uncharged phenolic amine rather than in the phenolic ammonium salt.

Über Muscaridin

AbstractThe present communication gives a preliminary description of the isolation of a new alkaloid from Amanita muscaria L. besides muscarin and acetylcholin. The constitution of this base, called muscaridin, is established as the quaternary trimethylammonium salt of 6 amino‐2,3‐dihydroxy‐hexan.

Über Muscaridin. II

A recent investigation of Kögl, Salemink and Schuller established the constitution of muscaridin as the quaternary trimethylammonium salt of 6‐amino‐2,3‐dihydroxyhexane.The present communication gives a preliminary description of a synthesis which started from 2,3‐dihydropyran, leading to racemic muscaridin. The synthetic product gives the same RF‐value and a fully similar infrared spectrum as the natural base.